Pending Policies - Surgery


Hematopoietic Stem-Cell Transplantation for Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

Number:SUR703.029

Effective Date:04-15-2018

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

Allogeneic hematopoietic stem cell transplantation may be considered medically necessary to treat chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) in patients with markers of poor-risk disease (refer to “Staging and Prognosis of CLL/SLL” below).

Staging and Prognosis of CLL/SLL:

For the laboratory key to (*1), (*2), (*3), refer to the listing following the Binet Classification System below:

Rai Staging System:

Stage 0 – Absolute lymphocytosis (*1) (>15,000/mm3) without adenopathy, hepatosplenomegaly, anemia (*2), or thrombocytopenia (*3). Median survival is >10 years. This stage is low risk and equivalent to Binet Clinical Stage A.

Stage I – Absolute lymphocytosis (*1) with lymphadenopathy without hepatosplenomegaly, anemia (*2), or thrombocytopenia (*3). Median survival is 7-9 years. This stage is intermediate risk and equivalent to Binet Clinical Stage B.

Stage II – Absolute lymphocytosis (*1) with lymphadenopathy with either hepatomegaly or splenomegaly, with or without lymphadenopathy. Median survival is 7-9 years. This stage is intermediate risk and equivalent to Binet Clinical Stage B.

Stage III – Absolute lymphocytosis (*1) and anemia (*2) with lymphadenopathy with either hepatomegaly or splenomegaly. Median survival is 1.5-5 years. This stage is high risk and equivalent to Binet Clinical Stage C.

Stage IV – Absolute lymphocytosis (*1) and thrombocytopenia (*3) (<100,000/mm3) with or without lymphadenopathy, hepatomegaly, splenomegaly, or anemia (*2). Median survival is 1.5-5 years. This stage is high risk and equivalent to Binet Clinical Stage C.

Binet Classification System (Lymphoid areas include cervical, axillary, inguinal, and spleen):

Clinical Stage A – No anemia (normal hemoglobin and platelets) (*2) or thrombocytopenia (*3) and fewer than 3 areas of lymphoid involvement. Median survival is >10 years. This stage is low to intermediate risk and equivalent to Rai Stages 0, I, and II.

Clinical Stage B – No anemia (normal hemoglobin and platelets) (*2) or thrombocytopenia (*3) with 3 or more areas of lymphoid involvement. Median survival is 7 years. This stage is intermediate risk and equivalent to Rai Stage I and II.

Clinical Stage C – Anemia (*2) and/or thrombocytopenia (*3) regardless of the number of areas of lymphoid enlargement. Median survival is 5 years. This stage is high risk and equivalent to Rai Stage III and IV.

Laboratory key to above listings:

(*1) Lymphocytosis = lymphocytes >15 x 109/L for 4 weeks.

(*2) Anemia = hemoglobin <100 g/dL.

(*3) Thrombocytopenia = platelets <100 x 109/L

Markers of Poor Prognosis of CLL/SLL:

Poor Prognosis Identified in a

Community Center

Poor Prognosis Identified in a

Specialized Center

Advanced Rai or Binet stage

IgVh wild type

Male sex

Expression of ZAP-70 protein

Atypical morphology or CLL or SLL

del 11q22-q23 (loss of ATM gene)

Peripheral lymphocyte doubling time <12 months

del 17p13 (loss of p53)

CD38+ (an antigen found on the surface of B-cell CLL cells)

trisomy 12

Elevated beta2-microglobulin level

Elevated serum CD23

Diffuse marrow histology

Elevated serum tumor necrosis factor-a

Elevated serum lactate dehydrogenase level

Elevated serum thymidine kinase

Fludarabine resistance IgVh wild type

Autologous hematopoietic stem cell transplantation is considered experimental, investigational and/or unproven to treat CLL/SLL.

NOTE: See Medical Policy SUR703.002 Hematopoietic Stem-Cell Transplantation (HSCT) or Additional Infusion Following Preparative Regimens (General Donor and Recipient Information) for detailed, descriptive information on HSCT related services.

Description:

Hematopoietic Stem-Cell Transplantation (HSCT)

HSCT refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in patients who receive bone-marrow-toxic doses of cytotoxic drugs with or without whole body radiation therapy. Hematopoietic stem-cells may be obtained from the transplant recipient (autologous HSCT) or from a donor (allogeneic HSCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates. Although cord blood is an allogeneic source, the stem-cells in it are antigenically “naive” and thus, are associated with a lower incidence of rejection or graft-versus-host disease (GVHD).

Immunologic compatibility between infused hematopoietic stem-cells and the recipient is not an issue in autologous HSCT. However, immunologic compatibility between donor and patient is a critical factor for achieving a good outcome of allogeneic HSCT. Compatibility is established by typing of human leukocyte antigens (HLA) using cellular, serologic, or molecular techniques. HLA refers to the tissue type expressed at the class I and class II loci on chromosome 6. Depending on the disease being treated, an acceptable donor will match the patient at all or most of the HLA loci (with the exception of umbilical cord blood).

Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

CLL and SLL are neoplasms of hematopoietic origin characterized by the accumulation of lymphocytes with a mature, generally well-differentiated morphology. In CLL, these cells accumulate in blood, bone marrow, lymph nodes, and spleen; in SLL, they are generally confined to lymph nodes. The Revised European-American/World Health Organization Classification of Lymphoid Neoplasms considers B-cell CLL and SLL a single disease entity.

CLL and SLL share many common features and are often referred to as blood and tissue counterparts of each other, respectively. Both tend to present as asymptomatic enlargement of the lymph nodes, tend to be indolent in nature, but can undergo transformation to a more aggressive form of disease (e.g., Richter transformation). The median age at diagnosis of CLL is approximately 72 years, but it may present in younger individuals, often as poor-risk disease with significantly reduced life expectancy.

Treatment regimens used for CLL are generally the same as those used for SLL, and treatment outcomes are comparable for both diseases. Both low- and intermediate-risk CLL and SLL demonstrate relatively good prognoses, with median survivals of 6 to 10 years; however, the median survival of high-risk CLL or SLL may only be 2 years. Although typically responsive to initial therapy, CLL and SLL are rarely cured by conventional therapy, and nearly all patients ultimately die of their disease. This natural disease history prompted investigation of HSCT as a possible curative regimen.

Staging and Prognosis of CLL and SLL:

Two scoring systems are used to determine stage and prognosis of patients with CLL or SLL. The Rai and Binet staging systems classify patients into 3 risk groups with different prognoses and are used to make therapeutic decisions. Because prognoses of patients vary within the different Rai and Binet classifications, other prognostic markers are used in conjunction with staging to determine clinical management. Use of these systems allows comparison of clinical results and establishment of therapeutic guidelines (Refer to systems in Coverage Section of this Medical Policy).

Regulatory Status

The U.S. Food and Drug Administration (FDA) regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research (CBER), under Code of Federal Regulation (CFR) title 21, parts 1270 and 1271. (25) Hematopoietic stem-cells are included in these regulations.

Rationale:

This policy was originally created in 1990, moved to this policy in 2010. The policy has been updated with reviews of the MedLine database. The most recent literature review was performed through April 14, 2017. While the coverage of this policy does not address myeloablative (MA) or reduced intensity conditioning (RIC) prior to hematopoietic stem-cell transplantation (HSCT), discussion of HSCT outcomes may be influenced by the type of preparative conditioning completed prior to the transplantation.

The original policy was based on 2 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessments, 1 from 1999 that examined autologous HSCT for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) (1); the other from 2002 on allogeneic HSCT (allo-HSCT) to treat CLL and SLL. (2) Both documents indicated that existing data were insufficient to permit scientific conclusions on the use of either procedure, and were limited by interstudy heterogeneity in patients’ baseline characteristics, procedural differences, sample size, and short follow-up. A direct comparative analysis from the International Bone Marrow Transplant Registry commissioned by TEC in 2002 to analyze allo-HSCT results was insufficient to permit scientific conclusions on the net health outcome of this procedure for relapsed or refractory CLL or SLL.

Reviews have discussed uncertainties with respect to the type of transplant (autologous versus allogeneic), the intensity of pretransplant conditioning, the optimal timing of transplantation in the disease course, the baseline patient characteristics that best predict likelihood of clinical benefit from transplant, and the long-term risks of adverse outcomes. (3-8) The conclusions reached in these reviews suggest that, although autologous HSCT may prolong survival in select patients with CLL or SLL (e.g., those with chemotherapy-sensitive malignancy who had a good response to front-line therapy and were transplanted early in the course of disease), it has not yet been shown to be curative.

Allogeneic HCST

Data compiled in review articles have suggested that myeloablative allo-HSCT has curative potential for CLL or SLL. (6-9) Long-term disease control (33%-65% overall survival [OS] at 3-6 years) due to a low rate of late recurrences has been observed in all published series, regardless of donor source or conditioning regimen. (10) However, high rates (24%-47%) of treatment-related mortality (TRM) discourage this approach in early- or lower-risk disease, particularly among older patients whose health status typically precludes the use of myeloablative conditioning.

The development of reduced-intensity conditioning (RIC) regimens has extended the use of allo-HSCT to older or less fit patients who account for the larger proportion of this disease than younger patients, as outlined in two 2009 review articles. (10, 11) Six published nonrandomized studies involved a total of 328 patients with advanced CLL who underwent RIC allo-HSCT using conditioning regimens that included fludarabine in various combinations including cyclophosphamide, busulfan, rituximab, alemtuzumab, and total body irradiation. (12-17) Most patients in these series were heavily pretreated, with a median of 3 to 5 courses of prior regimens. Among individual studies, 27% to 57% of patients had chemotherapy-refractory disease, genetic abnormalities including a 17p13 deletion, 11q22 deletion, and VH unmutated, or a combination of those characteristics. A substantial proportion in each study (18%-67%) received stem cells from a donor other than a human leukocyte antigen?identical sibling. Reported nonrelapsing mortality (NRM) associated primarily with graft-versus-host disease and its complications ranged from 2% at 100 days to 26% overall at median follow-up ranging from 1.7 to 5 years. OS rates ranged from 48% to 70% at follow-up that ranged from 2 to 5 years. Similar results were reported for progression-free survival (PFS), which was 34% to 58% at 2- to 5-year follow-up. Very similar results were reported from a phase 2 study published in 2010 of RIC allo-HSCT in patients (n=90; median age, 53 years; range, 27-65) with poor-risk CLL, defined as having one of the following: refractoriness or early relapse (i.e., <12 months) after purine-analogue therapy; relapse after autologous HSCT; or progressive disease in the presence of an unfavorable genetic marker (11q or 17p deletion, and/or unmutated immunoglobulin heavy-chain variable-region status and/or usage of the VH3-21 gene). (18) With a median follow-up of 46 months, 4-year NRM, event-free survival (EFS), and OS were 23%, 42%, and 65%, respectively. EFS estimates were similar for all genetic subsets, including those with a 17p deletion.

Section Summary: Allogeneic HSCT

No randomized controlled trials (RCTs) evaluating allo-HSCT in patients with CLL were identified. Data from nonrandomized studies found OS rates between 48% and 70% at 2 to 5 years and PFS rates of 34% to 58% at 2 to 5 years after allo- HSCT for poor-risk CLL. Despite not being randomized, these studies suggest that allo-HSCT can provide long-term disease control and OS in patients with poor-risk CLL and SLL.

Autologous HSCT

A 2015 systematic review of autologous HSCT as first-line consolidation in CLL included a literature search through November 2014. (19) Four RCTs in adults were selected. Outcomes included OS, PFS, EFS, and harms (adverse events, treatment-related mortality, secondary malignancies). In these 4 trials, 301 patients were randomized to the autologous HSCT arm and 299 to the control arm using first-line therapy without HSCT as consolidation. Autologous HSCT did not result in a statistically significant improvement in OS (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.62 to 1.33) or in PFS (HR=0.70; 95% CI, 0.32 to 1.52). There was a statistically significant improvement in EFS favoring autologous HSCT (HR=0.46; 95% CI, 0.26 to 0.83). A higher rate of secondary malignancy or treatment-related mortality was not associated with autologous HSCT.

A phase 3 European Intergroup RCT (2011) addressed autologous HSCT as second- or third-line treatment of CLL. (20) The trial compared autologous HSCT (n=112) and postinduction observation (n=111) for consolidation in patients with CLL who achieved a complete response (CR; 59% of total) or very good partial response (VGPR; 27% of total) following fludarabine-containing induction therapy. Overall, patients’ age ranged from 31 to 65 years and they presented with Binet stage A progressive (14%), B (66%), and C (20%) disease. The population either did not have a 17p deletion or 17p deletion status was unknown. Median EFS (the primary outcome) was 51 months (range, 40-62 months) in the autograft group and 24 months (range, 17-32 months) in the observation group; 5-year EFS was 42% and 24%, respectively (p<0.001). The relapse rate at 5-year follow-up was 54% in the autograft group and 76% in the observational group (p<0.001); median time to relapse requiring therapy or to death (whichever came first) was 65 months (range, 59-71 months) and 40 months (range, 25-56 months), respectively (p=0.002). OS probability at 5-year follow-up was 86% (95% CI, 77% to 94%) in the autograft arm and 84% (95% CI, 75% to 93%) in the observation arm (p=0.77), with no evidence of a plateau in the areas under the curve. There was no significant difference in NRM between groups (4% for autologous HSCT versus 0% for observation; p=0.33). Myelodysplastic syndrome (MDS) was observed at follow-up in 3 patients receiving an autograft and in 1 patient in the observational group.

In a subsequent 2014 report, authors of the European Intergroup RCT presented quality-of-life (QOL) findings from this trial. (21) Two secondary analyses were performed to further investigate the impact of HSCT and relapse on QOL. In the primary analysis, the authors demonstrate an adverse impact of HSCT on QOL, which was largest at 4 months and continued throughout the first year after randomization. Further, a sustained adverse impact of relapse on QOL was observed, which worsened over time. Thus, despite better disease control by autologous HSCT, the side effects turned the net effect toward inferior QOL in the first year and comparable QOL in the following 2 years after randomization.

Section Summary: Autologous HSCT

A systematic review of RCTs did not find that autologous HSCT as first-line consolidation therapy for CLL significantly improved OS or PFS compared with alternative treatments. An RCT on autologous HSCT as second- or third-line treatment of CLL did not find that HSCT improved the net health outcome.

Ongoing and Unpublished Clinical Trials

A search of ClinicalTrials.gov in December 2016 did not identify any ongoing or unpublished trials that would likely influence this review.

Practice Guidelines and Position Statements

American Society for Blood and Marrow Transplantation (ASBMT)

In 2015, the ASBMT published guidelines on indications for autologous and allogeneic HSCT for CLL. (22) Recommendations described the current consensus on use of HSCT within and outside of the clinical trial setting. Treatment recommendations are shown in Table 1.

Table 1: ASBMT 2015 Recommendations for Allogeneic and Autologous HSCT for CLL

Adult Indications

Allogeneic HSCT

Autologous HSCT

High risk, first or greater remission

C

N

T-cell, prolymphocytic leukemia

R

R

B-cell, prolymphocytic leukemia

R

R

Transformation to high-grade lymphoma

C

C

Table Key:

ASBMT: American Society for Blood and Marrow Transplantation;

C: standard of care, clinical evidence available,

CLL: chronic lymphocytic leukemia;

HSCT: hematopoietic stem-cell transplantation;

N: Not generally recommended;

R: standard of care, rare indication.

In 2016, ASBMT published clinical practice recommendations with additional detail on allo-HSCT for CLL. (23) Recommendations are shown in Table 2.

Table 2: ASBMT 2016 Recommendations for Allogeneic HSCT for CLL

Indications

Allogeneic HSCT

High Risk CLL

Not recommended in the first-line consolidation setting.

Not recommended for patients who relapse after first-line therapy and demonstrate sensitive disease after second line therapy (not BCR inhibitors).

Recommended for patients who relapse after first-line therapy, have refractory disease after second-line therapy (not BCR inhibitors) and show an objective response to BCR inhibitors or to a clinical trial.

Recommended for patients who relapse after first-line therapy, have refractory disease after second-line therapy (including BCR inhibitors but not BCL-2 inhibitors) and show an objective response to BCL-2 inhibitors or to a clinical trial.

Recommended when there is a lack of response or there is progression after BCL-2 inhibitors.

Richer Transformation

Recommended after achieving an objective response to anthracycline-based chemotherapy.

Purine Analogue Relapsed and/or Refractory Disease

Not recommended.

National Comprehensive Cancer Network (NCCN) Guidelines

Current NCCN guidelines (v.2.2017) for CLL and SLL state that allogeneic HSCT may be considered for patients (24):

With relapsed CLL or SLL and without a17p deletion or TP53 mutation,

With CLL or SLL, a response to treatment and with a complex karyotype,

With CLL (Rai stages 0-IV) or SLL (Lugano stages II-IV), after histologic transformation to diffuse large B-cell/Hodgkin lymphoma.

The current NCCN guidelines for CLL and SLL does not include autologous HSCT as a therapeutic option for CLL or SLL. (24).

Summary of Evidence

For individuals who have chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and markers of poor-risk disease who receive allogeneic hematopoietic stem-cell transplantation (allo-HSCT), the evidence includes single-arm prospective and registry-based studies as well as a BCBSA TEC Assessment. Relevant outcomes are overall survival, disease-specific survival, change in disease status, and treatment-related mortality and morbidity. Data have suggested that allo-HSCT can provide long-term disease control and overall survival in patients with poor-risk CLL/SLL. High rates of treatment-related morbidity discourage this approach in lower risk disease, particularly among older patients whose health status typically precludes the use of myeloablative conditioning. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have CLL/SLL who receive autologous HSCT, the evidence includes randomized controlled trials (RCTs), systematic reviews, and a Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment. Relevant outcomes are overall survival, disease-specific survival, change in disease status, and treatment-related mortality and morbidity. Autologous HSCT is feasible in younger patients but is not curative, particularly in those with poor-risk CLL. Studies of autologous HSCT published to date have not shown improvement in overall survival in patients with CLL/SLL, and results must be considered in the context of improved outcomes with the use of newer chemoimmunotherapy agents. Furthermore, evidence from the European Intergroup RCT has suggested quality-of-life issues are important in selecting patients for autologous HSCT and may dictate the management course for patients who are otherwise candidates for this approach. The evidence is insufficient to determine the effects of the technology on health outcomes.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

36511, 38204, 38205, 38206, 38207, 38208, 38209, 38210, 38211, 38212, 38213, 38214, 38215, 38220, 38221, 38222, 38230, 38232, 38240, 38241, 38242, 38243, 81265, 81266, 81267, 81268, 81370, 81371, 81372, 81373, 81374, 81375, 81376, 81377, 81378, 81379, 81380, 81381, 81382, 81383, 86805, 86806, 86807, 86808, 86812, 86813, 86816, 86817, 86821, 86822, 86825, 86826, 86828, 86829, 86830, 86831, 86832, 86833, 86834, 86835, 86849, 86950, 86985, 88240, 88241

HCPCS Codes

S2140, S2142, S2150

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.

A national coverage position for Medicare may have been changed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. High-Dose Chemotherapy with Autologous Stem-cell Support for Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (1999 February) 14(20):1-24.

2. High-Dose Chemotherapy plus Allogeneic Stem-cells to Treat Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (2002 June) 17(4):1-28.

3. Abbott BL. Chronic lymphocytic leukemia: recent advances in diagnosis and treatment. The Oncologist. Jan 2006; 11(1):21-30. PMID 16401710

4. Brugiatelli M, Bandini G, Barosi G, et al. Management of chronic lymphocytic leukemia: practice guidelines from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation. Haematologica. Dec 2006; 91(12):1662-73. PMID 17145603

5. Dreger P, Brand R, Michallet M. Autologous stem-cell transplantation for chronic lymphocytic leukemia. Semin Hematol. Oct 2007; 44(4):246-51. PMID 17961723

6. Gine E, Moreno C, Esteve J, et al. The role of stem-cell transplantation in chronic lymphocytic leukemia risk-adapted therapy. Best Pract Res Clin Haematol. Sep 2007; 20(3):529-43. PMID 17707838

7. Gribben JG. Role of allogeneic hematopoietic stem-cell transplantation in chronic lymphocytic leukemia. J Clin Oncol. Oct 20 2008; 26(30):4864-5. PMID 18794537

8. Kharfan-Dabaja MA, Anasetti C, Santos ES. Hematopoietic cell transplantation for chronic lymphocytic leukemia: an evolving concept. Biol Blood Marrow Transpl. Apr 2007; 13(4):373-85. PMID 17382245

9. Gladstone DE, Fuchs E. Hematopoietic stem cell transplantation for chronic lymphocytic leukemia. Curr Opin Oncol. Mar 2012; 24(2):176-81. PMID 22234253

10. Delgado J, Milligan DW, Dreger P. Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for prime time? Blood. Sep 24 2009; 114(13):2581-8. PMID 19641189

11. Dreger P. Allotransplantation for chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2009:602-9. PMID 20008245

12. Brown JR, Kim HT, Li S, et al. Predictors of improved progression-free survival after nonmyeloablative allogeneic stem-cell transplantation for advanced chronic lymphocytic leukemia. Biol Blood Marrow Transplant. Oct 2006; 12(10):1056-64. PMID 17084369

13. Delgado J, Thomson K, Russell N, et al. Results of alemtuzumab-based reduced-intensity allogeneic transplantation for chronic lymphocytic leukemia: a British Society of Blood and Marrow Transplantation Study. Blood. Feb 15 2006; 107(4):1724-30. PMID 16239425

14. Dreger P, Brand R, Hansz J, et al. Treatment-related mortality and graft-versus-leukemia activity after allogeneic stem-cell transplantation for chronic lymphocytic leukemia using intensity-reduced conditioning. Leukemia. May 2003; 17(5):841-8. PMID 12750695

15. Khouri IF, Saliba RM, Admirand J, et al. Graft-versus-leukaemia effect after non-myeloablative haematopoietic transplantation can overcome the unfavourable expression of ZAP-70 in refractory chronic lymphocytic leukaemia. Br J Haematol. May 2007; 137(4):355-63. PMID 17456058

16. Schetelig J, Thiede C, Bornhauser M, et al. Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group. J Clin Oncol. Jul 15 2003; 21(14):2747-53. PMID 12860954

17. Sorror ML, Storer BE, Sandmaier BM, et al. Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol. Oct 20 2008; 26(30):4912-20. PMID 18794548

18. Dreger P, Dohner H, Ritgen M, et al. Allogeneic stem-cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. Oct 7 2010; 116(14):2438-47. PMID 20595516

19. Reljic T, Kumar A, Djulbegovic B, et al. High-dose therapy and autologous hematopoietic cell transplantation as front-line consolidation in chronic lymphocytic leukemia: a systematic review. Bone Marrow Transplant. Aug 2015; 50(8):1144. PMID 26242579

20. Michallet M, Dreger P, Sutton L, et al. Autologous hematopoietic stem-cell transplantation in chronic lymphocytic leukemia: results of European intergroup randomized trial comparing autografting versus observation. Blood. Feb 3 2011; 117(5):1516-21. PMID 21106985

21. de Wreede LC, Watson M, van Os M, et al. Improved PFS after autologous stem cell transplantion does not translate into better Quality of Life in CLL: lessons from the randomized EBMT-Intergroup study. Am J Hematol. Feb 2004; 89(2):174-80. PMID 24123244

22. 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. Nov 2015; 21(11):1863-9. PMID 26256941

23. Kharfan-Dabaja MA, Kumar A, Behera M, et al. Systematic review of high dose chemotherapy and autologous haematopoietic stem-cell transplantation for chronic lymphocytic leukaemia: what is the published evidence? Br J Haematol. Dec 2007; 139(2):234-42. PMID 27660167

24. NCCN –Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (Version 2.2017). National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Available at: <www.nccn.org> (accessed April 12, 2017).

25. Food and Drug Administration (FDA). Tissue and Tissue Products (December 29, 2016). Available at http://www.fda.gov> (accessed April 14, 2017).

26. High-Dose Chemotherapy with Hematopoietic Stem-Cell Transplantation for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. (2017 January) Therapy 8.01.15.

Policy History:

Date Reason
4/15/2018 Reviewed. No changes.
6/1/2017 Document updated with literature review. Coverage unchanged.
5/15/2016 Reviewed. No changes.
5/1/2015 Document updated with literature review. The following was changed: Rai Staging System, Binet Classification System and Markers of Poor Prognosis moved from Description to Coverage Sections. Coverage unchanged. Title changed from Stem-Cell Transplant for Treatment of Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL).
2/1/2013 Document updated with literature review. The following was added as clarification to the medically necessary coverage: “markers of poor-risk disease.” Description and Rationale significantly revised.
4/1/2010 New medical document originating from: SUR703.017, Peripheral/Bone Marrow Stem-cell Transplantation (PSCT/BMT) for Non-Malignancies; SUR703.018, Peripheral/Bone Marrow Stem-cell Transplantation (PSCT/BMT) for Malignancies; SUR703.022, Cord Blood as a Source of Stem-cells (CBSC); SUR703.023, Donor Leukocyte Infusion (DLI); and SUR703.024, Tandem/Triple High-Dose Chemoradiotherapy with Stem-cell Support for Malignancies. Stem-cell transplant continues to be medically necessary when stated criteria are met. [NOTE: A link to the medical policies with the following titles can be found at the end of the medical policy SUR703.002, Stem-Cell Reinfusion or Transplantation Following Chemotherapy (General Donor and Recipient Information): Peripheral/Bone Marrow Stem-cell Transplantation (PSCT/BMT) for Non-Malignancies; Peripheral/Bone Marrow Stem-cell Transplantation (PSCT/BMT) for Malignancies; Cord Blood as a Source of Stem-cells; Donor Leukocyte Infusion (DLI); and Tandem/Triple High-Dose Chemoradiotherapy with Stem-cell Support for Malignancies.

Archived Document(s):

Back to Top