Medical Policy

 

Subject: Hematopoietic Stem Cell Transplantation for Multiple Myeloma and Other Plasma Cell Dyscrasias
Document #: TRANS.00023 Publish Date:    12/27/2017
Status: Revised Last Review Date:    11/02/2017

Description/Scope

This document addresses hematopoietic stem cell transplantation in multiple myeloma, amyloidosis and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes).

Note: For additional stem cell transplant information and criteria, see the applicable document(s):

Position Statement

Multiple Myeloma

Medically Necessary:

Autologous hematopoietic stem cell transplantation (AutoHSCT) for treatment of individuals with multiple myeloma is considered medically necessary when used as:

  1. As a single transplant (AutoHSCT); or
  2. As a tandem* transplant (two AutoHSCTs separated by 30 to 180 days); or
  3. As a repeat procedure (AutoHSCT greater than 180 days following a previous AutoHSCT); or
  4. As a pretreatment for a non-myeloablative allogeneic hematopoietic stem cell transplant; or
  5. As salvage therapy after:
    1. Primary graft failure; or
    2. Failure to engraft; or
    3. Rejection following an allogeneic HSCT.

Allogeneic (ablative or non-myeloablative) stem cell transplantation after a previous autologous stem cell transplant for treatment of individuals with multiple myeloma is considered medically necessary.

A planned tandem non-myeloablative allogeneic transplantation following an autologous transplantation is considered medically necessary for treatment of individuals with multiple myeloma. 

A repeat allogeneic (ablative or non-myeloablative) stem cell transplantation due to primary graft failure, failure to engraft or rejection is considered medically necessary.

Hematopoietic stem cell harvesting** for an anticipated but unscheduled transplant is considered medically necessary in individuals with multiple myeloma who meet one of the above criteria and for whom the treating physician documents that a future transplant is likely.
**Note: Hematopoietic stem cell harvesting does not include the transplant procedure.

*Tandem transplantation refers to a planned infusion (transplant) of previously harvested hematopoietic stem cells with a repeat hematopoietic stem cell infusion (transplant) that is performed within 6 months of the initial transplant. This is distinguished from a repeat transplantation requested or performed more than 6 months after the first transplant, and is used as salvage therapy after failure of initial transplantation or relapsed disease.

Investigational and Not Medically Necessary:

Allogeneic (ablative or non-myeloablative) stem cell transplantation or autologous stem cell transplantation is considered investigational and not medically necessary for individuals with multiple myeloma who do not meet the above criteria.

Hematopoietic stem cell harvesting for a future but unscheduled transplant is considered investigational and not medically necessary when the criteria above are not met.

A repeat allogeneic (ablative or non-myeloablative) stem cell transplantation due to persistent, progressive or relapsed disease is considered investigational and not medically necessary.

Three or more autologous hematopoietic stem cell transplantations within a 12-month period are considered investigational and not medically necessary.

Amyloidosis

Medically Necessary:

Autologous stem cell transplantation is considered medically necessary for individuals with primary amyloidosis (AL) who meet the following criteria:

Note: (If the individual has a preceding diagnosis of multiple myeloma, use the transplant criteria above for multiple myeloma).

  1. If the heart is involved with AL, the individual is asymptomatic or has compensated congestive heart failure; and
  2. Left ventricular ejection fraction (LVEF) greater than or equal to 45%; and
  3. Must have documented disease on biopsy without a preceding diagnosis of multiple myeloma.

A repeat autologous stem cell transplantation due to primary graft failure or failure to engraft is considered medically necessary.

Hematopoietic stem cell harvesting** for an anticipated but unscheduled transplant is considered medically necessary in individuals with amyloidosis who meet one of the above criteria and for whom the treating physician documents that a future transplant is likely.
**Note: Hematopoietic stem cell harvesting does not include the transplant procedure.

Investigational and Not Medically Necessary:

Autologous stem cell transplantation is considered investigational and not medically necessary in the treatment of primary amyloidosis in individuals with symptomatic heart failure regardless of the number of organs involved.

Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered investigational and not medically necessary for treatment of individuals with amyloidosis.

A tandem* autologous stem cell transplantation is considered investigational and not medically necessary for treatment of individuals with amyloidosis.

A repeat autologous stem cell transplantation due to persistent, progressive or relapsed disease is considered investigational and not medically necessary.

Hematopoietic stem cell harvesting for a future but unscheduled transplant is considered investigational and not medically necessary when the criteria above are not met.

* Tandem transplantation refers to a planned infusion (transplant) of previously harvested hematopoietic stem cells with a repeat hematopoietic stem cell infusion (transplant) that is performed within 6 months of the initial transplant. This is distinguished from a repeat transplantation requested or performed more than 6 months after the first transplant, and is used as salvage therapy after failure of initial transplantation or relapsed disease.

POEMS Syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes)

Medically Necessary:

Autologous stem cell transplantation is considered medically necessary for treatment of POEMS Syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) when diagnostic criteria for that syndrome are met.

A repeat autologous stem cell transplantation due to primary graft failure or failure to engraft is considered medically necessary.

Hematopoietic stem cell harvesting** for an anticipated but unscheduled transplant is considered medically necessary in individuals with POEMS syndrome who meet one of the above criteria and for whom the treating physician documents that a future transplant is likely.
**Note: Hematopoietic stem cell harvesting does not include the transplant procedure.

Investigational and Not Medically Necessary:

Autologous stem cell transplantation for treatment of individuals with POEMS Syndrome is considered investigational and not medically necessary when the above criteria are not met.

Allogeneic (ablative or non-myeloablative) stem cell transplantation for treatment of individuals with POEMS Syndrome is considered investigational and not medically necessary.

A tandem* autologous stem cell transplantation for treatment of individuals with POEMS Syndrome is considered investigational and not medically necessary.

A repeat autologous stem cell transplantation due to persistent, progressive or relapsed POEMS is considered investigational and not medically necessary.

Hematopoietic stem cell harvesting for a future but unscheduled transplant is considered investigational and not medically necessary when the criteria above are not met.

* Tandem transplantation refers to a planned infusion (transplant) of previously harvested hematopoietic stem cells with a repeat hematopoietic stem cell infusion (transplant) that is performed within 6 months of the initial transplant. This is distinguished from a repeat transplantation requested or performed more than 6 months after the first transplant, and is used as salvage therapy after failure of initial transplantation or relapsed disease.

Rationale

Multiple Myeloma

Multiple myeloma is a malignant disorder characterized by proliferation of mature plasma cells in the bone marrow that produce monoclonal immunoglobulin proteins. The proliferation of plasma cells leads to destruction of the bone and failure of the bone marrow and may cause nephropathy and neuropathy (Girnius, 2010). Standard treatment options include the use of alkylating agents such as melphalan, cyclophosphamide and corticosteroids as well as autologous and allogeneic hematopoietic stem cell transplantation. Improvements in newer treatments have resulted in an increase in 5-year survival from 25% in 1975 to 34% in 2003. Median survival rates have improved to 45 to 60 months as a result of newer treatment modalities that include pulse corticosteroids, dexamethasone, thalidomide, bortezomib and lenalidomide along with autologous and allogeneic stem cell transplantation (National Cancer Institute [NCI], 2017). There are ongoing studies to determine the optimal timing, combination and sequence of therapies and long-term benefits of therapy with the newer treatments.

Koreth and colleagues (2007) performed a meta-analysis of randomized controlled trials, comparing chemotherapy versus high-dose chemotherapy (HDT) with single autologous stem cell transplant. The nine trials that met the selection criteria (n=2411) started enrolling participants in the 1990s and included two studies that did not detect a survival benefit from high-dose chemotherapy. The study concluded that there is no significant difference in overall survival benefit to individuals given up-front HDT (p=0.4). Additionally, the use of peripheral blood stem cells (PBSCs) did not provide an overall survival benefit. However, a significant progression-free survival (PFS) benefit to individuals given up-front HDT (p=0.02) was reported. A significantly increased risk of treatment-related mortality for individuals receiving HDT was found (odds ratio 3.01, 95% confidence interval [CI], 1.64-5.50) in the group with autologous stem cell transplant. However, the effects of high-dose chemotherapy and autologous stem cell transplant may have been diluted by the fact that up to 55% of individuals in the standard chemotherapy group received high-dose chemotherapy with autologous stem cell transplant as salvage therapy when the multiple myeloma progressed. This could account for the lack of a significant difference in overall survival between the two groups in the study.

A multicenter randomized controlled study by Cavo (2007) compared single with double autologous stem cell transplants in 321 participants. Individuals undergoing tandem autologous transplantation were more likely than those with a single transplant to attain at least a near complete response (47% vs. 33%; p=0.008), to prolong relapse-free survival (median, 42 vs. 24 months; p<0.001), and extend event-free survival (median, 35 vs. 23 months; p=0.001). There was no significant difference between the groups in treatment-related mortality (3%-4%).

Few individuals are considered eligible for a second autologous stem cell transplant to treat multiple myeloma that has relapsed after a complete or partial remission that followed an initial autologous transplant. Thus, it is unlikely that prospective trials will ever be conducted to rigorously compare outcomes of this strategy with alternatives. Nevertheless, retrospective studies report durable complete or partial responses and extended survival for individuals treated this way, particularly when a long disease- or progression-free interval followed the first transplant.

Sibling or unrelated allogeneic transplants have several potential advantages relative to autologous transplants, including no chance that the transplant will reinfuse multiple myeloma cells and the possibility that donor cells may mediate immunologic antitumor effects. Several peer-reviewed, published case series report a complete response rates range from 22% to 67% after allogeneic transplant in individuals with multiple myeloma. A number of observations suggest that graft-vs-myeloma effects occur following allogeneic transplantation, including the identification of myeloma-specific cytotoxic T cells in transplant recipients and clinical responses to donor lymphocyte infusions.

A study published by Maloney (2003) included 54 individuals (median age 52 years; range 29-71) with previously treated multiple myeloma (52% refractory or relapsed disease) given an initial autologous stem cell transplant conditioned with 200 mg/m2 melphalan. Of these, 52 received a subsequent non-myeloablative allogeneic stem cell transplant. Investigators reported 78% overall survival (OS) at a median 552 days after allografting. Treatment achieved a complete remission (CR) in 57% and an overall response rate of 83%. Acute graft-versus-host disease (GVHD) developed in 38% of individuals (grades III/IV in 4 cases; grade II in all others), and chronic GVHD requiring therapy in 46%. Twelve participants died: 1 from viral infection after the initial autologous transplant, 2 from multiple myeloma progression (3 and 23 months post-mini-allogeneic transplant), 7 from GVHD, and 1 each from lung cancer and encephalopathy.

Bruno and colleagues (2007) reported results from a series of 162 participants with newly diagnosed multiple myeloma and who had at least one sibling. All participants received induction chemotherapy and an initial autologous stem cell transplant followed by a subsequent transplant. Forty-six out of 82 eligible participants without an HLA-identically matched sibling received a tandem autologous stem cell transplant. Fifty-eight out of 80 enrolled participants with an HLA-identical sibling received a nonmyeloablative stem cell transplant from the sibling. At a median follow-up of 45 months, the median overall survival (80 months vs. 54 months, p=0.01) and event-free survival (35 months vs. 29 months, p=0.02) were significantly different between individuals treated with tandem autologous stem cell transplants compared to those treated with autologous – allogeneic stem cell transplants.

A long-term analysis of autologous stem cell transplant (ASCT) alone versus ASCT followed by reduced-intensity conditioning (RIC) matched-related allogeneic transplant (auto-allo) for treatment of 357 individuals with multiple myeloma was reported by Björkstrand and colleagues (2011). The 249 individuals without an HLA-identical donor were assigned to the ASCT group and 108 who had a matched donor were assigned to the auto-allo group. A total of 91 individuals in the auto-allo cohort received the RIC allogeneic stem cell transplant (alloSCT) as planned. A total of 145 individuals in the ASCT cohort received a single transplant while 104 individuals received a tandem auto transplant. At 60 months after the first ASCT, based upon intention-to-treat (ITT) analysis, PFS of 35% in the auto-allo group was significantly better (p=0.001) than 18% in the ASCT group. Long-term OS was also significantly better for the auto-allo cohort at 60 months, 65% versus 58% in the ASCT group. The rate of CR for the auto-allo group was 51% and the ASCT group was 41% (p=0.020). The long-term results support the use of auto-allo transplant as treatment for individuals with previously untreated multiple myeloma (Björkstrand, 2011).

The National Comprehensive Cancer Network® (NCCN) Multiple Myeloma Clinical Practice Guideline (2018) notes autologous stem cell transplant is the standard of care after primary therapy and results in high response rates. Newer induction therapies involving lenalidomide, bortezomib or thalidomide have been improving overall response rates compared to combined vincristine, doxorubicin and dexamethasone (VAD). However, the exact timing and role for these therapies and their potential to be an alternative to transplant are being investigated. The guidelines also list (category 2A) the second cycle of a tandem transplant (within 6 months of the initial autologous stem cell transplant) as an option for individuals with partial response or stable disease as a result of the first autologous stem cell transplant. The guidelines state donor lymphocyte infusions (DLI) may be given to those who do not respond or to those who relapse after an allogeneic stem cell transplant.

Amyloidosis

In amyloidosis, amyloid fibrils deposit in various organs causing dysfunction (Girnius, 2010). There are various types of amyloidosis and the most common and rapidly progressive form is immunoglobulin light chain AL (primary) amyloidosis. Secondary or AA amyloidosis is commonly associated with other chronic conditions such as rheumatoid arthritis, autoinflammatory disorders or chronic infections. High-dose chemotherapy with autologous stem cell transplantation for primary (AL) amyloidosis targets the aberrant plasma cell clone to prevent further synthesis and deposition of the amyloid protein. Chemotherapeutic drug combinations such as melphalan plus prednisone (MP) or vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD), well-established regimens for myeloma are among the conventional therapies for those with primary amyloidosis. However, as is true for multiple myeloma, these regimens rarely cure individuals. Approximately 30% of individuals with amyloidosis responded to MP and median survival ranged from 1-2 years. VAD therapy is usually limited to those individuals without peripheral neuropathy or cardiomyopathy, both common complications of amyloidosis.

Since results of standard therapies for primary amyloidosis are unsatisfactory, clinical studies were begun on high-dose chemotherapy with autologous stem cell support (HDC AuSCT). Data showing HDC AuSCT improved outcomes for those with myeloma provided an additional rationale for studies on individuals with amyloidosis. The number of organs involved is strongly associated with mortality. Individuals with three or more organs involved are considered poor candidates for transplantation. There is sufficient evidence from case series studies to demonstrate a net health benefit to support the use of HDC AuSCT in individuals with primary amyloidosis that is limited to one or two organs and without symptomatic heart failure. In a review of 92 individuals with amyloidosis treated with autologous stem cell transplant, the treatment related mortality (TRM) was high at 23% (Goodman, 2006). However, when a subset analysis was performed, “the number of organs involved by amyloid correlated strongly with TRM (p<0.0005); all 8 patients with 4 or 5 organs involved died by day 100, as did 6 of 17 patients with 3 organs involved.” Goodman and colleagues concluded limiting inclusion criteria to “one or two amyloidotic organs have the potential to reduce TRM to rates approaching those seen in myeloma.” With improvements observed in multiple myeloma, newer treatment modalities that include dexamethasone, thalidomide, bortezomib and lenalidomide are being studied as treatments for primary amyloidosis.

Analysis of long-term data collected prospectively on 421 consecutive individuals with AL amyloidosis treated with autologous stem cell transplant at one center was provided by Cibeira (2011). Thirty percent (125 individuals) had AL involvement in one organ, 27% (115 individuals) had two involved organs, and 43% (181 individuals) had AL involvement in three or more organs. One-year survival was not met in 81 participants. With a median follow-up of 6.9 years, 43% of the 340 evaluable individuals achieved CR and organ response was noted in 78%. For those in CR, the median event-free survival (EFS) was 8.3 years and the OS was 13.2 years, respectively. Forty individuals initially in CR (28%) experienced a relapse. Fifty-two percent of the 195 individuals that did not obtain CR had median EFS of 2 years and an OS of 5.9 years. Univariate analysis noted that the absence of cardiac involvement (p=0.005) was a significant predictor of CR. The overall treatment-related mortality rate was 5.6% within the last 5 years of the study, and 11.4% overall. The authors noted autologous stem cell transplant results in organ response and CR while improving treatment mortality rates.

Sanchorawala and colleagues (2007) reported long-term survival of 80 participants treated with autologous transplants at a single institution. Seventeen individuals died within the first year as a result of treatment-related complications or progressive disease. Sixty-three individuals were evaluable at 1 year with 32 (51%) in a complete hematologic response. The median survival is 57 months for all 80 participants, and 18 (23%) are alive at 10 or more years after transplant. The survival at 10 years is 53% and the median survival for individuals who achieved a complete hematologic response has not yet been reached.

In a case-controlled study of 126 participants with primary systemic amyloidosis by Dispenzieri (2004), data suggested improved outcomes in select individuals with high dose chemotherapy and stem cell transplant compared to treatment with chemotherapy agents. Each cohort consisted of 63 participants. Transplant-related mortality was 13% (8 individuals). Fifty participants in the control group have died. Median follow-up for the control group is 8.8 years compared to 3.8 years for the treatment group. Based on 95% confidence intervals, the estimated 4-year survival for the transplant group was 71% compared to 41% for controls.

A retrospective review of the Center for International Blood and Marrow Transplant Research (CIBMTR) database resulted in 107 individuals with comprehensive information available for analysis (Vesole, 2006). All 107 participants were treated with various preparatory regimens and autologous stem cell transplants as treatment for primary amyloidosis. Seventy-seven individuals had organ-specific data available and responses at day 100 were noted in at least one organ system in 28 (36%). Thirty-four of 107 individuals had a hematologic response at 1 year (17 [16%] with complete response; 17 [16%] partial response; 33 [31%] had stable disease and 11 [10%] had progressive disease. The median overall survival for all individuals was 47.2 months. Overall survival at 1 year was 66% and 56% at 3 years. Transplant related mortality was 27% (29/107 individuals). Further analysis revealed the year of transplantation to be the only statistically significant predictor (p=0.02) of survival. Those who were treated with transplants more recently had superior outcomes compared to earlier transplants.

According to Girnius and colleagues (2010) approximately 12-15% of individuals with multiple myeloma develop systemic amyloid light-chain amyloidosis. The resulting organ dysfunction resulting from the deposition of amyloid fibrils can occur when the bone marrow has 5-10% clonal plasma cells. Girnius (2010) reported results from a retrospective study of individuals with both amyloidosis and multiple myeloma treated with autologous stem cell transplant at a single center. The authors concluded “in terms of response and recurrence, patients with amyloid light chain amyloidosis and myeloma behave more like patients with myeloma only.”

The NCCN Systemic Light Chain Amyloidosis Clinical Practice Guideline (V1.2018) indicates that high-dose melphalan followed by autologous stem cell transplant is a therapeutic option for amyloidosis. However, individuals have to be carefully selected because of significant treatment-related mortality. In 2017, NCCN added a recommendation to assess for stem cell candidacy in newly diagnosed individuals. NCCN also recommended reassessing candidacy following two cycles of systemic therapy if not a candidate at initial diagnosis.

POEMS Syndrome

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) is an acronym for a rare multisystem disorder associated with plasma cell dyscrasia where quality of life typically deteriorates as neuropathy progresses. POEMS syndrome is a compound disorder which is portrayed by monoclonal plasma cell proliferative disorder, polyneuropathy and an elevation in vascular endothelial growth factor (VEGF) and other proinflammatory cytokines. The prevalence of POEMS remains uncertain; with an estimated occurrence of 0.3 cases per 100,000 individual, POEMS disorder occurs less frequently in Western countries according to a Cochrane Review (Kuwabara, 2008b). In the last several years, a variety of treatment options have been utilized including: chemotherapy, radiation therapy, intravenous immunoglobulin, plasma exchange, corticosteroids, and stem cell transplantation. Treatment with irradiation or surgical resection of solitary plasmacytoma has been utilized. Systemic chemotherapy similar to therapies used to treat multiple myeloma is recommended for individuals with widespread osteosclerotic lesions or no detectable bone lesion (Chee, 2010; Dispenzieri, 2007; Kuwabara, 2008b). For diffuse disease indicated by multiple bone lesions or a positive iliac crest biopsy for clonal plasma cells, high-dose chemotherapy with autologous stem cell transplantation is recommended (Kuwabara, 2008b). However, there is no established treatment regimen for this syndrome based on randomized controlled trials (Kuwabara, 2008b).

Multiple case series and individual case reports (Kuwabara, 2008b; Laurenti, 2008) have demonstrated improvement in function and reduction of symptoms following high-dose chemotherapy and autologous stem cell transplant. In the largest case series to date, Kuwabara (2008a) and associates reported clinical improvement at 6 months in all 9 individuals with POEMS treated with autologous peripheral blood stem cell transplant (AuPBSCT). Neurologic improvement began at 3 months, and all individuals showed substantial neurologic recovery during the next 3 months. Three initially chairbound individuals regained the ability to walk at 6 months. Nerve conduction studies showed significant increases in conduction velocities and amplitudes within 6 months of treatment. The median follow-up period was 20 months (8-49 months). At the end of follow-up periods, neuropathy was still improving, and no individuals had recurrence of symptoms.

A Cochrane Review (Kuwabara, 2008b) noted the lack of randomized controlled trials for this rare syndrome involving “demyelinating and axonal mixed neuropathy with multiorgan involvement.” Due to the rarity of this condition, Phase II and III trials have not been conducted. The data from eight retrospective case series were analyzed. The authors noted substantial stabilization or improvement in neurological symptoms as well as other features associated with POEMS with autologous stem cell transplantation. Also, the pooled mortality figure is estimated 2/45 (4%) which appears higher than the 2% transplant related mortality (TRM) in individuals with multiple myeloma, but lower than TRM of 14% in primary amyloidosis. The authors concluded “recent case series and case reports have shown that high-dose chemotherapy with autologous peripheral blood stem cell transplantation is efficacious treatment for POEMS syndrome, although long-term outcomes have not yet been elucidated” (Kuwabara, 2008). In an update of 30 individuals with POEMS who had autologous stem cell transplants, Dispenzieri (2008) noted a higher rate of treatment related morbidity or engraftment syndrome (ES).

Poor Graft Function

Poor graft function or graft failure is one of the major causes of morbidity and mortality after hematopoietic stem cell transplantation. Poor graft function is defined as slow or incomplete recovery of blood cell counts following a stem cell transplant or decreasing blood counts after initially successful hematopoietic engraftment following a stem cell transplant. There are various options for the management of poor graft function. Stem cell “boost” is a non-standardized term that is used to describe an infusion of additional hematopoietic stem cells to an individual who has undergone recent hematopoietic stem cell transplantation and has poor graft function (Larocca, 2006). The infusion of additional hematopoietic stem cells is to mitigate either graft failure or rejection with or without immunosuppression. This process may include the collection of additional hematopoietic stem cells from a donor and infusion into the transplant recipient. Note that a "boost" is distinct from a repeat transplant and that there may be separate medical necessity criteria for a repeat transplant.

Other Considerations

In 2015, the American Society for Blood and Marrow Transplantation (Majhail and colleagues) issued guidelines on indications for autologous and allogeneic hematopoietic cell transplantation. Definitions used for classifying indications were: standard of care (S); standard of care, clinical evidence available (C); standard of care, rare indication (R); Developmental (D); and not generally recommended (N). Indications for hematopoietic cell transplantation in adults (generally 18 years of age or older) include the following classifications for plasma cell disorders:

Giralt and colleagues (2015) for the American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma proposed guidelines for the use of salvage hematopoietic stem cell transplantation for the treatment of multiple myeloma. The group’s consensus committee agreed on the following guideline statements:

Consensus Guidelines for Salvage Autologous Hematopoietic Stem Cell Transplantation (HCT):

  1. In transplantation-eligible patients relapsing after primary therapy that did NOT include an autologous HCT, high-dose therapy with autologous HCT as part of salvage therapy should be considered standard.
  2. High-dose therapy and autologous HCT should be considered appropriate therapy for any patients relapsing after primary therapy that includes an autologous HCT with initial remission duration of more than 18 months.
  3. High-dose therapy and autologous HCT can be used as a bridging strategy to allogeneic HCT.
  4. The role of postsalvage HCT maintenance needs to be explored in the context of well-designed prospective trials that should include new agents, such as monoclonal antibodies, IMiDs, and oral proteasome inhibitors.
  5. Autologous HCT consolidation should be explored as a strategy to develop novel conditioning regimens or post-HCT strategies in patients with short remission (less than 18 months).
  6. Prospective randomized trials need to be performed to define the role of salvage autologous HCT in patients with MM relapsing after primary therapy comparing to “best non-HCT” therapy.

The committee also stressed the importance of collecting enough hematopoietic stem cells to perform two transplantations early in the course of the disease.

Consensus Guidelines Regarding Role of Allogeneic HCT in Relapsed Myeloma

  1. Allogeneic HCT should be considered appropriate therapy for any eligible patient with early relapse (less than 24 months) after primary therapy that included an autologous HCT or with high-risk features (ie, cytogenetics, extramedullary disease, plasma cell leukemia, or high lactate dehydrogenase) provided that they responded favorably to salvage therapy before allogeneic HCT.
  2. Whenever possible, allogeneic HCT should be performed in the context of a clinical trial.
  3. The role of postallogeneic HCT maintenance therapy needs to be further explored.
  4. Prospective randomized trials need to be performed to define the role of salvage allogeneic HCT in patients with MM relapsing after primary therapy.

Shah and colleagues (2015) for the American Society for Blood and Marrow Transplantation issued guidelines for hematopoietic stem cell transplantation for multiple myeloma. The document includes the following statements:

  1. We recommend HDC and auto-HCT as consolidative therapy for patients with multiple myeloma (grade A recommendation)
  2. Though prospective evidence is lacking, we recommend consideration of a first auto-HCT for patients with refractory disease (grade C recommendation)
  3. We recommend serious consideration of a clinical trial for patients with high-risk cytogenetics, particularly del17p or t(4:14) (grade C recommendation)
  4. Second auto-HCT is a safe and efficacious treatment modality for relapsed multiple myeloma and should be considered (grade B)
  5. Patients with longer progression-free interval after first auto-HCT have better outcomes after salvage second auto-HCT. It is recommended that the minimum length of remission be at least 12 months for consideration of a second auto-HCT as salvage therapy (grade D). The role of maintenance therapy after salvage second-HCT in unclear.
  6. Upfront myeloablative allo-HCT is not routinely recommended (grade A). It may be appropriate for further study in young patients with very high-risk MM, in the context of a clinical trial.
  7. Planned reduced-intensity conditioning (RIC)-allo HCT after auto-HCT has not been found to be superior in the majority of clinical trials and is, therefore, not recommended over auto-HCT (grade A). Its role in high-risk subgroups requires further study.
  8. Allo-HCT salvage therapy for relapsed MM has not been shown to be superior to salvage auto-HCT and is not routinely recommended outside of a clinical trial (grade D). For younger patients with a good performance status, allo-HCT can be considered, ideally in the context of a clinical trial.

Levels of evidence were assessed and a grade assigned to each recommendation following the criteria below:

Levels of Evidence
1++ 
High-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias.
1+  Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias.
1-  Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias.
2++  High-quality systematic reviews of case-control or cohort studies; high-quality case-control or cohort studies with a very low risk of confounding, bias, or chance and a high
probability that the relationship is causal.
2+  Well-conducted case-control or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal.
2-  Case-control or cohort studies with a high risk of confounding, bias, or chance and a significant risk that the relationship is not causal.
3  Nonanalytic studies, eg, case reports or case series.
Expert opinion.

RCT indicates randomized controlled trial. Reproduced from: A new system for grading recommendations in evidence based guidelines, Harbour R, Miller J. BMJ 2001; 323:334-336.

Grades of Recommendation
A 
At least 1 meta-analysis, systematic review, or RCT rated as 1++ and directly applicable to the target population or a systematic review of RCTs or a body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results.
B   A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results or extrapolated evidence from studies rated as 1++ or 1+.
A body of evidence including studies rated as 2+, directly applicable to the target population, and demonstrating overall consistency of results or extrapolated evidence from studies rated as 2++.
Evidence level 3 or 4 or extrapolated evidence from studies rated as 2+.

Reproduced from: A new system for grading recommendations in evidence based guidelines, Harbour R, Miller J. BMJ 2001; 323:334-336.

Background/Overview

HSCT is an important therapeutic modality for many malignant and nonmalignant hematologic diseases and its applicability continues to expand as its use in established therapies is refined and new indications are identified. In addition, the number individuals who could benefit from HSCT has increased due to advancements, such as reduced intensity conditioning regimens, which have made HSCT safer (Majhail, 2015). However, the risks associated with transplant-associated morbidity and mortality remain significant. Most transplant centers utilize forums, boards or conferences where the treatment options of individual HSCT candidates are discussed (Majhail, 2015). Okamoto (2017) notes:

The medical decision-making process for a transplant procedure is complex which requires assessing several factors besides the underlying indication for transplantation. Those include patient/disease factors, and transplant factors such as planed conditioning/graft-versus-host disease (GVHD) prophylaxis and stem cell source. Patient factors include their overall health and comorbidities, prior therapies, and how patients responded to those therapies, age, and disease/disease risk.

There are a number of clinical assessment and prognostic tools which evaluate individuals based upon multiple factors. The earlier, simpler tools, such as the Charlson Comorbidity Index (CCI) were useful in predicting outcomes, but lacked the sensitivity of subsequent tools such as the HCT-specific comorbidity index (HCT-CI) The HCT-CI score has been validated in multiple HSCT settings to independently predict non-relapse mortality (NRM) rates by weighting 17 relevant comorbidities. The HCT-CI was further enhanced by the incorporation of some laboratory biomarkers into an augmented version. While these tools provide valuable prognostic information, the decision to transplant is unique to each individual and needs to include a specific risk-benefit analysis in partnership with the individual’s physicians and other caregivers.

Multiple Myeloma

Multiple myeloma is a systemic malignancy of plasma cells that accumulate in the bone marrow which results in destruction of bone and failure of the bone marrow. Multiple myeloma is highly treatable but rarely curable. However, when it presents as a solitary plasmacytoma of bone or as an extramedullary plasmacytoma it is potentially curable. The National Cancer Institute estimates more than 30,280 new cases of multiple myeloma will be diagnosed in the United States in 2017 and more than 12,950 will die from this disease. The disease is staged by estimating the myeloma tumor cell mass on the basis of the amount of monoclonal (or myeloma) protein (M-protein) in the serum and/or urine along with various clinical parameters, such as the hemoglobin and serum calcium concentrations, the number of lytic bone lesions, and the presence or absence of renal failure. The stage of the disease at presentation is a strong determinant of survival, but has little influence on the choice of therapy since almost all individuals (except for those with solitary bone tumors or extramedullary plasmacytomas) have generalized disease. The age and general health of the individual, prior therapy and the presence of complications of the disease influence treatment selection. The median survival in the prechemotherapy era was about 7 months. Multiple myeloma has demonstrated chemosensitivity to initial treatment or treatment for relapsed disease. After the introduction of chemotherapy, prognosis improved significantly with a median survival of 24 to 30 months and a 10-year survival of 3%. Drugs such as bortezomib along with immunomodulatory derivatives, thalidomide and lenalidomide, have been used as a treatment for multiple myeloma and have contributed to advances in therapy and prognosis (Cavo, 2011; NCCN, 2018; NCI, 2017).

Amyloidosis

Primary amyloidosis, also called AL, is a disorder in which insoluble immunoglobulin light chain protein fibrils are deposited in tissues and organs, impairing their function. The cause of primary amyloidosis is unknown, but the condition is related to the abnormal production of immunoglobulins by a type of immune cell called plasma cells. AL may occur with multiple myeloma and is caused by abnormal plasma cell in the bone marrow. The symptoms depend on the organs affected by the deposits, which can include the tongue, intestines, skeletal and smooth muscles, nerves, skin, ligaments, heart, liver, spleen, and kidneys. The deposits infiltrate the affected organs, causing them to lose resilience and become stiff, which decreases their ability to function. Multiple myeloma, including other plasma cell neoplasms, may cause amyloidosis (NCI, 2017). Risk factors for development of this disease have not been identified.

POEMS Syndrome

POEMS is an acronym for the dominant presentations of the syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) which may also be called Crow-Fukase Syndrome and Takatsuki syndrome (Dispenzieri, 2007). There are additional clinical features that are not included in the acronym, which include elevated levels of VEGF, sclerotic bone lesions, Castleman Disease, papilledema, peripheral edema, ascites, effusions, thrombocytosis, polycythemia, fatigue and clubbing for this syndrome where etiology is uncertain (Dispenzieri, 2007).

POEMS syndrome:

The modality used to treat POEMS syndrome is dependent on the individuals underlying blood cell disorder. Based on the presentation and complexity of the syndrome, a variety of specialists (e.g., neurologist, hematologist, dermatologist, and endocrinologist) are used with several different treatment regimens. Treatment of POEMS syndrome is utilized to halt the production of bone marrow cells that can create complications in other parts of the body. A standard treatment has not been identified; options such as radiation therapy, chemotherapy, corticosteroids, immunoglobulin therapy, plasma exchange and AuPBSCT have been utilized for this condition.

Hematopoietic Stem Cell Transplant

Hematopoietic stem cell transplantation is a process which includes mobilization, harvesting, and transplant of stem cells after the administration of high dose chemotherapy (HDC) and/or radiotherapy. High-dose chemotherapy involves the administration of cytotoxic agents using doses several times greater than the standard therapeutic dose. In some cases, whole body or localized radiotherapy is also given and is included in the term HDC when applicable. The rationale for HDC is that many cytotoxic agents act according to a steep dose-response curve. Thus, small increments in dosage will result in relatively large increases in tumor cell kill. Increasing the dosage also increases the incidence and severity of adverse effects related primarily to bone marrow ablation (e.g., opportunistic infections, hemorrhage, or organ failure). Bone marrow ablation is the most significant side effect of HDC. As a result, HDC is accompanied by a re-infusion of hematopoietic stem cells, which are primitive cells capable of replication and formation into mature blood cells, in order to repopulate the marrow. The potential donors of stem cells include:

  1. Autologous - Stem cells can be harvested from the individual’s own bone marrow prior to the cytotoxic therapy
  2. Allogeneic - Stem cells harvested from a healthy, histocompatible donor. (Note: this document does not require that a specific level of histocompatibility be present as part of the medical necessity evaluation).

Donor stem cells, either autologous or allogeneic, can be collected from either the bone marrow or the peripheral blood. Stem cells may be harvested from the peripheral blood using a pheresis procedure. To increase the number of stem cells in the peripheral circulation, donors may be pretreated with a course of chemotherapy or hematopoietic growth factors, or both.

In addition, blood harvested from the umbilical cord and placenta shortly after delivery of neonates contains stem and progenitor cells. Although cord blood is an allogeneic source, these stem cells are antigenically “naïve” and thus, are associated with a lower incidence of rejection or graft versus host disease.

The most appropriate stem cell source for a particular individual depends upon his or her disease, treatment history, and the availability of a compatible donor. The most appropriate source of stem cells for each individual must balance the risks of graft failure and re-infusion of malignant cells in autologous procedures, the risks of graft rejection, and graft versus host disease in allogeneic procedures.

While some HDC protocols can be administered on an outpatient basis, an inpatient stay may be required. Individuals receiving whole body radiotherapy, typically those receiving an allogeneic transplant, might require prolonged hospitalization.

While the intensity of the regimens used for conditioning in conventional HDC varies, collectively they have been termed “myeloablative.” Several less intense conditioning regimens have been developed recently and rely more on immunosuppression than cytotoxic effects to permit engraftment of donor cells. These regimens, collectively termed “non-myeloablative”, also vary in intensity with substantial overlap between the ranges for “myeloablative” and “non-myeloablative” regimens. Studies have shown that donor allogeneic stem cells can engraft in recipients using less-intensive conditioning regimens that are sufficiently immunosuppressive to permit graft-host tolerance. This manifests as a stable mixed donor-host hematopoietic chimerism. Once chimerism has developed, a further infusion of donor leukocytes may be given to eradicate malignant cells by inducing a graft vs. tumor effect. Non-myeloablative allogeneic transplants, also referred to as “mini-transplant” or “transplant lite”, are thought to be potentially as effective as conventional HDC followed by an allogeneic stem cell transplantation (AlloBMT), but with decreased morbidity and mortality related to the less intense non-myeloablative chemotherapy conditioning regimen. Consequently, for individuals with malignancies who are eligible for conventional HDC/AlloBMT, conditioning with milder, non-myeloablative regimens (NM-AlloBMT) represents a technical modification of an established procedure.

Tandem high-dose or non-myeloablative chemotherapy with autologous and/or allogeneic stem cell support is the planned administration of two cycles of high-dose chemotherapy, alone or with total body irradiation, each of which is followed by re-infusion of stem cells. Despite treatment with high-dose chemotherapy, many individuals with advanced malignancies eventually relapse, indicating the presence of residual neoplastic cells. The hypothesis is that eradication of residual tumor cells can be achieved using multiple cycles of myeloablative or non-myeloablative chemotherapy with stem cell support.

Definitions

Ablative: A very high dose of a treatment, calculated to kill a tumor or malignant cells.

Allogeneic hematopoietic stem cell transplantation: Infusion of hematopoietic stem cells obtained from a genetically different individual (“donor”).

Autologous hematopoietic stem cell transplantation: Infusion of previously harvested hematopoietic stem cells to the same individual from whom they were harvested.

Bone marrow: A spongy tissue located within flat bones, including the hip and breast bones and the skull. This tissue contains stem cells, the precursors of platelets, red blood cells, and white cells.

Chemotherapy: Medical treatment of a disease, particularly cancer, with drugs or other chemicals.

Chimerism: Cell populations derived from different individuals, which may be mixed or complete.

Complete response/remission (CR): The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured.

Cytotoxic: Destructive to cells.

Failure to engraft: When the hematopoietic stem cells infused during a stem cell transplant do not grow and function adequately in the bone marrow.

Graft-versus-host disease: A life-threatening complication of bone marrow transplants in which the donated marrow causes an immune reaction against the recipient’s body.

Hematopoietic stem cells: Primitive cells capable of replication and formation into mature blood cells in order to repopulate the bone marrow.

High-dose or myeloablative chemotherapy (HDC): The administration of cytotoxic agents using doses several times greater than the standard therapeutic dose.

HLA (human leukocyte antigen): A group of protein molecules located on bone marrow cells that can provoke an immune response.

Non-myeloablative chemotherapy: Less intense chemotherapy conditioning regimens, which rely more on immunosuppression than cytotoxic effects to permit engraftment of donor cells; may also be called reduced intensity conditioning.

Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment; also called partial remission.

Primary graft failure: When the hematopoietic stem cells infused during a stem cell transplant do not grow and function adequately in the bone marrow.

Primary refractory disease: Cancer that does not respond at the beginning of treatment; also called resistant disease.

Relapse: After a period of improvement, the return of signs and symptoms of cancer.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met for autologous transplants:

CPT

 

38206

Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous

38207-38215

Transplant preparation of hematopoietic progenitor cells [includes codes 38207, 38208, 38209, 38210, 38211, 38212, 38213, 38214, 38215; when specified for autologous transplant]

38232

Bone marrow harvesting for transplantation; autologous

38241

Hematopoietic progenitor cell (HPC); autologous transplantation

 

 

HCPCS

 

S2150

Bone marrow or blood-derived peripheral stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including pheresis and cell preparation/storage, marrow ablative therapy, drugs, supplies, hospitalization with outpatient follow-up, medical/surgical, diagnostic, emergency, and rehabilitative services, and the number of days of pre- and post-transplant care in the global definition [when specified as autologous]

 

 

ICD-10 Procedure

 

 

Autologous transplantation

30230G0-30263G0

Transfusion of autologous bone marrow [by site and approach; includes codes 30230G0, 30233G0, 30240G0, 30243G0, 30250G0, 30253G0, 30260G0, 30263G0]

30230Y0-30263Y0

Transfusion of autologous hematopoietic stem cells [by site and approach; includes codes 30230Y0, 30233Y0, 30240Y0, 30243Y0, 30250Y0, 30253Y0, 30260Y0, 30263Y0]

 

Pheresis [when specified as autologous]

6A550ZV

Pheresis of hematopoietic stem cells, single [when specified as autologous]

6A551ZV

Pheresis of hematopoietic stem cells, multiple [when specified as autologous]

 

 

ICD-10 Diagnosis

 

C90.00-C90.32

Multiple myeloma, plasmacytoma, immunoproliferative neoplasms

D47.Z9

Other specified neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue

E85.0-E85.9

Amyloidosis

E88.09

Other disorders of plasma-protein metabolism, not elsewhere classified [when specified as POEMS syndrome]

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above, when criteria are not met; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

When services may be Medically Necessary when criteria are met for allogeneic transplants:

CPT

 

38204

Management of recipient hematopoietic progenitor cell donor search and cell acquisition

38205

Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic

38207-38215

Transplant preparation of hematopoietic progenitor cells [includes codes 38207, 38208, 38209, 38210, 38211, 38212, 38213, 38214, 38215; when specified for allogeneic transplant]

38230

Bone marrow harvesting for transplantation; allogeneic

38240

Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor

38243

Hematopoietic progenitor cell (HPC); HPC boost

 

 

HCPCS

 

S2142

Cord blood-derived stem cell transplantation, allogeneic

S2150

Bone marrow or blood-derived peripheral stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including pheresis and cell preparation/storage, marrow ablative therapy, drugs, supplies, hospitalization with outpatient follow-up, medical/surgical, diagnostic, emergency, and rehabilitative services, and the number of days of pre- and post-transplant care in the global definition [when specified as allogeneic]

 

 

ICD-10 Procedure

 

 

Allogeneic transplantation

30230G2-30243G4

Transfusion of allogeneic bone marrow, related, unrelated or unspecified into peripheral or central vein [by approach; includes codes 30230G2, 30230G3, 30230G4, 30233G2, 30233G3, 30233G4, 30240G2, 30240G3, 30240G4, 30243G2, 30243G3, 30243G4]

30250G1-30263G1

Transfusion of nonautologous bone marrow into peripheral or central artery [by approach; includes codes 30250G1, 30253G1, 30260G1, 30263G1]

30230X2-30243X4

Transfusion of allogeneic cord blood stem cells, related, unrelated or unspecified into peripheral or central vein [by approach; includes codes 30230X2, 30230X3, 30230X4, 30233X2, 30233X3, 30233X4, 30240X2, 30240X3, 30240X4, 30243X2, 30243X3, 30243X4]

30250X1-30263X1

Transfusion of nonautologous cord blood stem cells into peripheral or central artery [by approach; includes codes 30250X1, 30253X1, 30260X1, 30263X1]

30230Y2-30243Y4

Transfusion of allogeneic hematopoietic stem cells, related, unrelated or unspecified into peripheral or central vein [by approach; includes codes 30230Y2, 30230Y3, 30230Y4, 30233Y2, 30233Y3, 30233Y4, 30240Y2, 30240Y3, 30240Y4, 30243Y2, 30243Y3, 30243Y4]

30250Y1-30263Y1

Transfusion of nonautologous hematopoietic stem cells into peripheral or central artery [by approach; includes codes 30250Y1, 30253Y1, 30260Y1, 30263Y1]

 

Pheresis [when specified as allogeneic]

6A550ZV

Pheresis of hematopoietic stem cells, single [when specified as allogeneic]

6A551ZV

Pheresis of hematopoietic stem cells, multiple [when specified as allogeneic]

 

 

ICD-10 Diagnosis

 

C90.00-C90.32

Multiple myeloma, plasmacytoma, immunoproliferative neoplasms

D47.Z9

Other specified neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above, when criteria are not met; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

When services are also Investigational and Not Medically Necessary:
For the procedure codes listed above for allogeneic transplants, for the following diagnosis codes, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

ICD-10 Diagnosis

 

E85.0-E85.9

Amyloidosis

E88.09

Other disorders of plasma-protein metabolism, not elsewhere classified [when specified as POEMS syndrome]

References

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Government Agency, Medical Society, and Other Authoritative Publications:

  1. Centers for Medicare and Medicaid Services. National Coverage Determination: Stem Cell Transplantation. NCD #110.23. Effective January 27, 2016. Available at: https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=45&ncdver=5&bc=AgAAQAAAAAAA&. Accessed on September 28, 2017.
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  4. Kuwabara S, Dispenzieri A, Arimura K, Misawa S. Treatment for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. Cochrane Database Syst Rev. 2012;(6):CD006828.
  5. Majhail NS, Farnia SH, Carpenter PA, et al. Indications for autologous and allogeneic hematopoietic cell transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015; 21(11):1863-1869.
  6. National Cancer Institute. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®): Treatment. Last modified October 20, 2017. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/myeloma/healthprofessional. Accessed on November 6, 2017.
  7. NCCN Clinical Practice Guidelines in Oncology™: © 2017. National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on October 9, 2017.
    • Multiple Myeloma (V.2.2018). October 2, 2017.
    • Systemic Light Chain Amyloidosis (V.1.2018). September 6, 2017.
  8. Shah N, Callander N, Ganguly S, et al. American Society for Blood and Marrow Transplantation. Hematopoietic stem cell transplantation for multiple myeloma: Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015; (7):1155-1166.
Websites for Additional Information
  1. American Cancer Society. Stem Cell Transplant for Cancer. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/stem-cell-transplant.html. Accessed on September 14, 2017.

  2. American Society for Blood and Bone Marrow Transplantation. Available at: http://www.asbmt.org/. Accessed on September 14, 2017.

  3. National Cancer Institute. Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers. Reviewed August 12, 2013. Available at: http://www.cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant. Accessed on September 14, 2017.

  4. National Organization for Rare Disorders (NORD). POEMS Syndrome. Published 2012. Available at: https://rarediseases.org/rare-diseases/poems-syndrome/. Accessed on September 28, 2017.

Index

 

Amyloidosis

Crow-Fukase syndrome

Hematopoietic Stem Cell Transplant (HSCT)

Mini-Transplant

Multiple Myeloma (MM)

Non-Myeloablative Stem Cell Transplant

Peripheral Blood Stem Cell

POEMS syndrome

Stem Cell Support (SCS)

Stem Cell Transplant (SCT)

Takatsuki syndrome

 

Document History

Status

Date

Action

Revised

11/02/2017

Medical Policy & Technology Assessment Committee (MPTAC) review.

Revised

11/01/2017

Hematology/Oncology Subcommittee review. The document header wording updated from “Current Effective Date” to “Publish Date”. Removed individual selection criteria. Updated Rationale, Background, References and Websites sections.

Revised

11/03/2016

MPTAC review.

Revised

11/02/2016

Hematology/Oncology Subcommittee review. Multiple occurrences of “transplant” replaced with “transplantation” in position statement. Formatting updated in position statement. Rationale, Background, Definitions, Reference and Index sections updated.

 

10/01/2016

Updated Coding section with 10/01/2016 ICD-10-PCS procedure code changes.

Reviewed

11/05/2015

MPTAC review.

Reviewed

11/04/2015

Hematology/Oncology Subcommittee review. Updated Rationale, Background and Reference sections. Removed ICD-9 codes from Coding section.

Reviewed

11/13/2014

MPTAC review.

Reviewed

11/12/2014

Hematology/Oncology Subcommittee review. Updated Rationale, References, Definitions and Websites.

Revised

11/14/2013

MPTAC review.

Revised

11/13/2013

Hematology/Oncology Subcommittee review. Clarified medically necessary criterion for planned tandem transplantation in multiple myeloma.  POEMS – clarified existing investigational and not medically necessary criterion and added a separate criterion for allogeneic stem cell transplant.  Updated Rationale, References, Definitions and Websites.

Revised

11/08/2012

MPTAC review.

Revised

11/07/2012

Hematology/Oncology Subcommittee review. Clarified Position Statements for multiple myeloma and amyloidosis. Added investigational and not medically necessary indication for three or more autologous stem cell transplants within a twelve-month period for multiple myeloma. Removed number of involved number of organs criterion for amyloidosis. Updated Rationale, References, Definitions and Websites.

Revised

11/17/2011

MPTAC review.

Revised

11/16/2011

Hematology/Oncology Subcommittee review. Clarified medically necessary indication for primary (AL) amyloidosis. Added medically necessary stem cell harvest Position Statement for POEMS. Clarified investigational and not medically necessary stem cell harvest criteria. Updated Rationale, Background, References and Websites. Updated Coding section with 01/01/2012 CPT changes.

Revised

11/18/2010

MPTAC review.

Revised

11/17/2010

Hematology/Oncology Subcommittee review. Title changed to Hematopoietic Stem Cell Transplantation for Multiple Myeloma and Other Plasma Cell Dyscrasias. Clarified medically necessary indications for multiple myeloma. Addition of medically necessary indication for POEMS Syndrome and graft failure or failure to engraft. Addition of not medically necessary statements for treatments of POEMS Syndrome with allogeneic transplant, tandem transplant, transplant for progressive/relapsed disease and stem cell harvest only without a planned future transplant. Rationale, Background, Coding, References and Websites updated.

Revised

11/19/2009

MPTAC review.

Revised

11/18/2009

Hematology/Oncology Subcommittee review.  Title changed. Removed “suitably matched” language from criteria. Added medical necessity criteria for hematopoietic stem harvest for multiple myeloma and amyloidosis. Clarified investigational and not medically necessary statement for prophylactic stem cell harvest for multiple myeloma and amyloidosis. Rationale, background, references and websites updated.

 

05/21/2009

Updated rationale to include information about stem cell “boosts”.

Revised

11/20/2008

MPTAC review.

Revised

11/19/2008

Hematology/Oncology Subcommittee review. Updated rationale, references, coding and websites. Clarified Individual Selection Criteria.

 

10/01/2008

Updated Coding section with 10/01/2008 ICD-9 changes.

 

01/01/2008

Updated Coding section with 01/01/2008 HCPCS changes; removed HCPCS G0267 deleted 12/31/2007.

Revised

11/29/2007

MPTAC review.

Revised

11/28/2007

Hematology/Oncology Subcommittee review. Updated references, websites. Removed separate medical necessity statement for tandem autologous stem cell transplant. Clarified medical necessity statements for tandem transplants. The phrase “investigational/not medically necessary” was clarified to read “investigational and not medically necessary.”

 

05/17/2007

Added note to cross reference TRANS.00016 Umbilical Cord Blood Progenitor Cell Collection, Storage and Transplantation.

Revised

12/07/2006

MPTAC review. 

Revised

12/06/2006

Hematology/Oncology Subcommittee review. Addition of med nec statement for primary graft failure.

Revised

06/08/2006

MPTAC review. 

Revised

06/07/2006

Hematology/Oncology Subcommittee review. Revision to general patient selection criteria.

Revised

12/01/2005

MPTAC review. 

Revised

11/30/2005

Hematology/Oncology Subcommittee. Revision to general patient selection criteria and clarification to multiple myeloma criteria.

 

11/22/2005

Added reference for Centers for Medicare and Medicaid Services (CMS) – National Coverage Determination (NCD).

Reviewed

07/14/2005

MPTAC review.

Revised

04/28/2005

MPTAC review.  Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.

Pre-Merger Organization

Last Review Date

Document Number

Title

Anthem, Inc.

10/28/2004

TRANS.00002

Stem Cell Transplant following Chemotherapy for Malignant Diseases

WellPoint Health Networks, Inc.

12/02/2004

7.11.02

Autologous Bone Marrow Transplantation or Peripheral Blood Stem Cell Support (PBSCS) for Malignancies

 

12/02/2004

7.11.03

Allogeneic Bone Marrow or Stem Cell Transplantation

 

12/02/2004

7.11.05

Mini-Transplants

 

06/24/2004

7.11.06

Second Autologous Bone Marrow Transplantation for Peripheral Blood Stem Cell Support (PBSCS) in Multiple Myeloma

 

12/02/2004

Clinical Guideline

Bone Marrow Transplant for  Multiple Myeloma

 

12/02/2004

Clinical Guideline

Bone Marrow Transplant for Amyloidosis

 

12/02/2004

Clinical Guideline

Second (Repeat) Bone Marrow/Stem Cell Transplant