BlueCross and BlueShield of Montana Medical Policy/Codes
Stem-Cell Transplant (SCT) for Treatment of Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)
Chapter: Medicine: Treatments
Current Effective Date: December 27, 2013
Original Effective Date: February 15, 2012
Publish Date: September 27, 2013
Revised Dates: March 22, 2012; September 13, 2013
Description

Chronic lymphocytic leukemia (CLL) (also known as B-cell CLL) and small lymphocytic lymphoma (SLL) are neoplasms of hematopoietic origin characterized by the accumulation of lymphocytes (white blood cells) with a mature, generally well-differentiated morphology. There is a slow increase of the lymphocytes. In CLL, these cells accumulate in the blood, marrow, lymph nodes, liver, and spleen, while in SLL they are generally confined to the lymph nodes. Eventually the cancer causes the bone marrow to fail. The Revised European-American/WHO (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 occur in older individuals (around age 70) and present as asymptomatic enlargement of the lymph nodes. Both tend to be indolent in nature but can undergo transformation to a more aggressive form of disease (e.g., Richter’s transformation). The disease is most common in those of Russian or East European descent. The cause is unknown, with no links to radiation, cancer-causing chemicals, or viruses.

Treatment regimens used for CLL are generally the same as those used for SLL, and outcomes of treatment are comparable for the two diseases. Both low- and intermediate-risk CLL and SLL demonstrate relatively good prognoses with median survivals of 6-10 years, while the median survival of high-risk CLL or SLL may be only two 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 history prompted investigation of hematopoietic stem-cell transplantation (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 or classification systems classify patients into three risk groups with different prognoses and are used to make therapeutic decisions. The integration of the Rai and Binet systems are the recommendation of a National Cancer Institute (NCI)-sponsored Working Group to standardize guidelines related to eligibility, response, and toxic effects of proposed treatments in both clinical trials and general practice settings. Use of these systems allows comparison of clinical results and establishment of therapeutic guidelines.

Rai Staging System:

  • Stage 0 – Absolute lymphocytosis* (>15,000/mm3) without adenopathy, hepatosplenomegaly, anemia**, or thrombocytopenia***. Median survival is >10 years. This stage is low risk and equivalent to Binet Clinical Stage A.
  • Stage I – Absolute lymphocytosis* with lymphadenopathy without hepatosplenomegaly, anemia**, or thrombocytopenia***. Median survival is 7-9 years. This stage is intermediate risk and equivalent to Binet Clinical Stage B.
  • Stage II – Absolute lymphocytosis* 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* and anemia** 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* and thrombocytopenia*** (<100,000/mm3) with or without lymphadenopathy, hepatomegaly, splenomegaly, or anemia**. 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** or thrombocytopenia*** 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** or thrombocytopenia*** 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 – No anemia** and/or thrombocytopenia*** 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:

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

**   Anemia = hemoglobin <100 g/dL.

*** Thrombocytopenia = platelets <100 x 109/L

Because prognosis of patients varies within the different Rai and Binet staging or classification systems, other prognostic markers are used in conjunction with staging to determine clinical management. These markers of poor prognosis in CLL or SLL are summarized (adapted from the NCI –sponsored Working Group) below, according to availability in clinical centers. Specialized Centers are normally academia and/or specialized laboratories involved in clinical trials; however, Community Centers are available at large for the general community to access.

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

 

Policy

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.

Coverage

Coverage for evaluation and subsequent single treatment by stem-cell transplant (SCT) (using bone marrow, peripheral blood, or umbilical cord blood as a stem-cell source), derived from a specific donor category, and following a chemotherapy regimen for treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are identified in the grids below.

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL):

Autologous:

Is considered experimental, investigational and unproven.

Allogeneic:

May be considered medically necessary for patients with markers of poor-risk disease, which includes those patients: 

  • In first remission and at high-risk for relapse of CLL, orIn second or greater remission, or
  • With relapsed or refractory CLL.

Tandem or Triple Stem-Cell Transplant:

Is considered experimental, investigational and unproven.

Donor Leukocyte Infusion:

Is considered experimental, investigational and unproven.

SMALL LYMPHOCYTIC LYMPHOMA (SLL):

Autologous:

Is considered experimental, investigational and unproven.

Allogeneic:

May be considered medically necessary for patients with markers of poor-risk disease, which includes those patients: 

  • In first remission and at high-risk for relapse of SLL orIn second or greater remission, or
  • With relapsed or refractory SLL.

Tandem or Triple Stem-Cell Transplant:

Is considered experimental, investigational and unproven.

Donor Leukocyte Infusion:

Is considered experimental, investigational and unproven.

NOTE:  Short tandem repeat (STR) markers may be utilized in pre-stem-cell transplant testing of the donor and recipient DNA profiles as a way to assess the status of the donor cell engraftment following the stem-cell transplantation.

Rationale

High-dose chemotherapy (HDC) followed by hematopoietic stem-cell transplant (HSCT) or stem-cell support (SCS) (i.e., blood or marrow) is an effective treatment modality for many patients with certain malignancies and non-malignancies. The rationale of this treatment approach is to provide a very dose-intensive treatment in order to eradicate malignant cells followed by rescue with peripheral blood, umbilical cord blood, or bone marrow stem-cells.

A coverage position was created in 2000; this section of the current policy has been substantially revised, and has been updated with searches of the MedLine database through August 2012. The following is a summary of the key literature to date.

When the policy was created, it was based on two Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessments, one from 1999 on autologous hematopoietic stem-cell transplantation (autologous HSCT, auto-HSCT) for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (1); the other from 2002 on allogeneic hematopoietic stem-cell transplantation (allogeneic HSCT, allo-HSCT) to treat CLL or SLL. (2) Both documents indicated that existing data were insufficient to permit scientific conclusions regarding the use of either procedure, limited by inter study heterogeneity in patient’s baseline characteristics, procedural differences, sample size, and short follow-up. A direct comparative analysis from the International Bone Marrow Transplant Registry (IBMTR) commissioned by BCBSA 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.

Literature searches conducted between 2002 and December 2008 found no randomized trials of HSCT compared with conventional-dose therapy for CLL or SLL. Recent reviews discuss uncertainties with respect to the type of transplant (autologous vs. 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 while auto-HSCT may prolong survival in selected patients with CLL or SLL, for example, those with chemotherapy-sensitive malignancy who had a good response to front-line therapy and transplanted early in the course of disease, it has not yet been shown to be curative.

Autologous Hematopoietic Stem Cell Transplant (auto-HSCT)

A systematic review of auto-HSCT for CLL or SLL included 9 studies (total n=361, 292 of which were transplanted) identified from a search of MedLine databases. (9) Studies were included if they were full-publication English language reports of prospective randomized, non-randomized, or single-arm design. The analysis suggested that while auto-HSCT may achieve significant clinical response rates (74-100%) with relatively low treatment-related mortality (TRM) (0–9%), molecular remissions are typically short-lived, with subsequent relapse. Overall survival (OS) ranged from 68% at 3-years’ follow-up to 58% at 6 years. Secondary myelodysplasia and myelodysplastic syndrome (MDS) that may progress to frank acute myelogenous leukemia (AML) has been reported in 5-12% of patients in some studies of auto-HSCT, which suggests caution in considering this approach, especially given the indolent nature of CLL or SLL. The authors of the review concluded that in the absence of randomized, comparative studies, it is uncertain whether auto-HSCT is superior to conventional chemotherapy (or current chemo-immunotherapy) combinations as first-line consolidation treatment in CLL or SLL patients, regardless of disease risk, or as salvage therapy in those with relapsed disease.

The conclusions of the systematic review of auto-HSCT outlined above are congruent with results of a Phase III randomized trial published in 2010 that compared auto-HSCT (n=112) or post-induction observation (n=111) for consolidation in patients with CLL who were in complete remission (CR; 59% of total) or very good partial remission (PR; 27% of total) following fludarabine-containing induction therapy. (10) Patient age ranged from 31-65 years, with Binet stage A progressive (14%), B (66%), and C (20%) disease. None were known to have 17p deletion; 45% were known to not carry 17p deletion, but that status was unknown in 54% of all patients. The primary outcome, median event-free survival (EFS), was 51 months (range: 40-62 months) in the autograft group, compared to 24 months (range: 17-32 months) in the observed group; the 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 versus 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). Overall survival probability at 5-year follow-up was 86% (95% confidence interval [CI]: 77-94%) in the autograft arm, versus 84% (95% CI: 75-93%) in the observation arm (p=0.77), with no evidence of a plateau in the curves. There was no significant difference in non-relapse mortality (NRM) between groups, 4% in the auto-HSCT group and 0% in the observation group (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.

A subsequent prospective, randomized clinical trial assessed the efficacy of auto-HSCT in previously untreated CLL patients. (11) A total of 244 patients (181 males) of median age 56 years (range 31-66 years) had Binet stage B (n=185) or C (n=56) disease. Among enrollees, 237 started planned therapy, 6 of whom discontinued. All 231 patients underwent induction chemotherapy; 103 (45%) entered CR and were randomly allocated to auto-HSCT (n=52) or observation (n=53). The 3-year estimated OS rates were 98% (95% CI: 94%, 100%) in the observation arm, and 96% (95% CI: 90%, 100%) in the HSCT arm (p=0.73). The estimated hazard ration (HR) for death was 1.2 (95% CI: 0.3, 3.8) in the HSCT arm relative to the observation arm (p=0.82). During the 36 months after randomization, HSCT was associated, on average, with an extra 9 months without clinical symptoms or blood signs of CLL progression (32 ± 1 month) compared with observation (23 ± 2 months). An editorial that accompanied this report suggests using auto-HSCT in this setting may prolong time to progression compared with observation, but that because OS is not improved, auto-HSCT remains experimental, investigational and unproven for CLL or SLL patients. (12, 13)

Allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT)

Given that auto-HSCT based on myeloablative conditioning regimens has not been demonstrated to be a curative treatment of CLL or SLL, alternative modalities have been sought. Allo-HSCT has been under investigation for the past two decades based on a potent graft-versus-leukemia (GVL) effect expressed as a permanently active cellular immune therapy in the recipient, independent of chemotherapy-related cytotoxicity.

Data compiled in numerous review articles suggest that myeloablative allo-HSCT has curative potential for CLL or SLL. (6-8) Long-term disease control (33-65% OS at 3 to 6 years) due to a low rate of late recurrences has been observed in all published series, regardless of donor source or conditioning regimen. (14) 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 several recent review articles. (7, 14, 15) 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 that included cyclophosphamide, busulfan, rituximab, alemtuzumab, and total-body irradiation. (16-21) The majority of patients in these series were heavily pretreated, with a median of 3-5 courses of prior regimens. Among individual studies, 27-57% of patients had chemotherapy-refractory disease, genetic abnormalities including del 17p13, del 11q22, 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- (HLA-) identical sibling. Reported NRM, associated primarily with graft-versus-host disease (GVHD) and its complications, ranged from 2% at 100 days to 26% overall at median follow-up that ranged from 1.7 years to 5 years. Overall survival rates ranged from 48-70% at follow-up that ranged from 2-5 years. Similar results were reported for progression-free survival (PFS), 34-58% at 2-5 year follow-up. Very similar results were reported from a Phase II study published in 2010 of RIC allogeneic HSCT in patients (n=90; median age 53 years, range: 27-65 years) with poor-risk CLL, defined as having 1 of the following: refractoriness or early relapse (i.e., less than 12 months) after purine-analog therapy; relapse after auto-HSCT; or, progressive disease in the presence of an unfavorable genetic marker (11q or 17p deletion, and/or unmutated IgVh status and/or usage of the VH3-21 gene). (22) With a median follow-up of 46 months, 4-year NRM, EFS, and OS were 23%, 42%, and 65%, respectively. EFS was similar for all genetic subsets, including those with a 17p deletion mutation.

Clinical Guidelines

European Group for Blood and Marrow Transplantation (EBMT):

In June 2005, the EBMT convened a consensus panel to identify situations in which allo-HSCT is indicated for patients with CLL. (24) Information for this evidence-based consensus was based on a MedLine search; meeting abstracts, and unpublished investigator-derived data. The panel considered four key issues:

  • Does graft-versus-leukemia (GVL) activity in CLL exist?
  • If yes, is it effective in high-risk CLL?
  • What is the success rate of allo-HSCT in CLL?
  • Which prognostic risk level justifies allo-HSCT?

The EBMT panel concluded that there is sound evidence that GVL activity is effective and represents the main contributor to durable disease control after allo-HSCT, even in poor-risk patients. It further concluded that long-term disease-free survival and possibly cure may be achieved in 33-67% of patients who undergo allo-HSCT for poor-risk CLL. While allo-HSCT for CLL is a procedure with evidence-based efficacy for poor-risk CLL, evidence is not sufficient to identify a generally superior conditioning regimen. The optimum choice of conditioning regimens may vary: in the presence of older age, comorbidity and sensitive disease; RIC regimens might be appropriate, whereas myeloablative regimens might be preferable in younger patients with good performance status but poorly controlled disease. The EBMT statement further suggests that these cases be discussed with a transplant center as early as possible to avoid extensive cytotoxic pretreatment or disease transformation. Furthermore, because the optimum transplant strategy may vary according to the clinical situation, it should be defined whenever possible in approved prospective clinical protocols.

It should be noted that the consensus panel has not discussed this topic since 2005.

National Cancer Institute (NCI) Working Group on CLL:

In 1988 and 1996, a National Cancer Institute Working Group (NCI-WG) on CLL published guidelines for the design and conduct of clinical trials to facilitate comparisons between treatments and establish definitions that could be used in scientific studies on the biology of this disease. The U.S. Food and Drug Administration (FDA) also adopted these guidelines in their evaluation and approval of new agents. An updated version of the NCI-WG guidelines has been published that provides management recommendations based on new prognostic markers, diagnostic parameters, and treatment options. (25)  In August 2012, the NCI Database indicated over 130 Phase II/III trials in the treatment of CLL, first-line, second-line, relapsed or refractory disease.

National Comprehensive Cancer Network (NCCN) Guidelines:

Current NCCN Guidelines for non-Hodgkin’s lymphoma (NHL) do not include auto-HSCT as a therapeutic option in CLL or SLL. (26) NCCN indicates that allo-HSCT (conditioning regimen unspecified) may be considered, preferably in a clinical trial, for patients younger than age 70 years with high-risk disease (Rai high risk, or del17p) or as salvage treatment in those with progressive or relapsed disease.

National Cancer Institute (NCI) Clinical Trials Database (PDQ®):

In August 2012, the NCI Clinical Trials Database indicated numerous Phase II/III trials that focused on a variety of hematopoietic SCT approaches for treatment of CLL or SLL, primarily relapsed or refractory disease, second-line therapy or more.

Summary for Auto-HSCT and Allo-HSCT

A substantial body of evidence from single-arm prospective and registry-based studies suggests allogeneic HSCT can provide long-term disease control and overall survival in patients with poor-risk CLL or SLL and otherwise dismal prognosis. This conclusion is supported by clinical input from transplant specialists as noted below. Until recently, it has been unclear what patient- and disease-specific characteristics can be used to select patients who could benefit from allo-HSCT compared to those for whom less-intense or no therapy may be indicated. This question has been addressed by investigations of cytogenetic and molecular abnormalities that can be associated with differential response to various therapies. (23)

Autologous HSCT is feasible in younger patients but is not curative, particularly in those with poor-risk CLL. None of the single-arm or registry studies of autologous HSCT published to date has shown a plateau in OS at 4 to 6 years post-transplant. It may result in prolongation of overall survival, compared with conventional therapy, but this must be considered in the context of improved outcomes using conventional chemoimmunotherapy.

Additional Infusion Treatments for CLL or SLL

Tandem or triple stem-cell transplant for CLL or SLL is considered experimental, investigational, and unproven due to lack of adequate evidence in published peer-reviewed medical literature of safety and effectiveness.

There are inadequate data regarding the efficacy of donor leukocyte infusion (DLI) for CLL or SLL. It is unlikely that sufficient prospective clinical trials will ever be conducted to rigorously compare outcome strategies using DLI for refractory hematologic malignancies post allo-HSCT other than AML or chronic myeloid leukemia (CML), since there are so few patients who would be eligible. Yet there is evidence from other types of studies that there is a graft-vs-malignancy effect after a nonmyeloablative allotransplant for these types of malignancies. While the risks of adverse outcomes are substantial, DLI may be considered a reasonable therapy for patients with hematologic malignancies who relapse after a previous medically necessary allo-HSCT. The benefit of DLI may exceed the harm for a specific selected patient.

Summary for Tandem or Triple SCT and DLI

Based on a search of peer reviewed literature in the MedLine database, through August 2012, there were no new clinical trial publications or any additional information that would change our coverage position; therefore, tandem or triple stem-cell transplant and DLI remain experimental, investigational and unproven for the treatment of CLL or SLL.

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. 

ICD-9 Codes

41.00, 41.01, 41.02, 41.03, 41.04, 41.05, 41.06, 41.07, 41.08, 41.09, 41.91, 99.25, 99.74, 99.79, 204.10, 204.11, 204.80, 204.81, 204.90, 204.91

ICD-10 Codes

C91.10, C91.11, C91.30, C91.31, C91.50, C91.51, C91.60, C91.61, C91.A0, C91.A1, C91.Z0, C91.Z1, C91.90, C91.91, 30230G0, 30230G1, 30233G0, 30233G1, 30240G0, 30240G1, 30243G0, 30243G1, 30250G0, 30250G0, 30250G1, 30253G0, 30253G1, 30260G0, 30260G1, 30263G0, 30263G1, 3E03005, 3E03305, 3E04005, 3E04305, 3E05005, 3E05305, 3E06005, 3E06305, 6A550Z2, 6A551Z2, 6A550ZT, 6A550ZV, 6A551ZT, 6A551ZV

Procedural Codes: 36511, 38204, 38205, 38206, 38207, 38208, 38209, 38210, 38211, 38212, 38213, 38214, 38215, 38220, 38221, 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, 86849, 86950, 86985, 88240, 88241, S2140, S2142, S2150
References
  1. HDC/AuSCS in the Treatment of CLL or SLL. 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 2006; 11(1):21-30.
  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 2006; 91(12):1662-73.
  5. Dreger P, Brand R, Michallet M. Autologous stem-cell transplantation for chronic lymphocytic leukemia. Semin Hematol 2007; 44(4):246-51.
  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 2007; 20(3):529-43.
  7. Gribben JG. Role of allogeneic hematopoietic stem-cell transplantation in chronic lymphocytic leukemia. J Clin Oncol 2008; 26(30):4864-5.
  8. Kharfan-Dabaja MA, Anasetti C, Santos ES. Hematopoietic cell transplantation for chronic lymphocytic leukemia: an evolving concept. Biol Blood Marrow Transpl 2007; 13(4):373-85.
  9. 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 2007; 139(2):234-42.
  10. 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 2011; 117(5):1516-21.
  11. Sutton L, Chevret S, Tournilhac O et al. Autologous stem-cell transplantation as a first-line treatment strategy for chronic lymphocytic leukemia: a multicenter, randomized, controlled trial from the SFGM-TC and GFLLC. Blood 2011; 117(23):6109-19.
  12. Montserrat E, Gribben JG. Autografting CLL: the game is over! Blood 2011; 117(23):6057-8.
  13. Garcia-Escobar I, Sepulveda J, Castellano D et al. Therapeutic management of chronic lymphocytic leukaemia: state of the art and future perspectives. Crit Rev Oncol Hematol 2011; 80(1):100-13.
  14. Delgado J, Milligan DW, Dreger P. Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for prime time? Blood 2009; 114(13):2581-8.
  15. Dreger P. Allotransplantation for chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2009:602-9.
  16. 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 2006; 12(10):1056-64.
  17. 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 2006; 107(4):1724-30.
  18. 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 2003; 17(5):841-8.
  19. 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 2007; 137(4):355-63.
  20. 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 2003; 21(14):2747-53.
  21. 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 2008; 26(30):4912-20.
  22. 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 2010; 116(14):2438-47.
  23. Kipps TJ. Chronic lymphocytic leukemia: advances in assessing prognosis and therapy. American Society of Clinical Oncology (ASCO) Education Book 2009:385-93.
  24. Dreger P, Corradini P, Kimby E et al. Indications for allogeneic stem-cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus. Leukemia 2007; 21(1):12-7.
  25. Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111(12):5446-56.
  26. NCCN – Non-Hodgkin’s Lymphoma Version 3.2012. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Available at: www.nccn.org (accessed 2012 August 24).
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  28. High-Dose Chemotherapy with Hematopoietic Stem-Cell Transplantation for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. (2012 January) Therapy 8.01.15.
  29. Donor Leukocyte Infusion for Hematologic Malignancies that Relapse after Allogeneic Stem-Cell Transplant. Chicago, Illinois: Blue Cross Blue Shield Association – Medical Policy Reference Manual (2012 May) Medicine 2.03.03.
History
October 2011 New Policy for BCBSMT
March 2012 Policy reviewed with literature search; no change to policy statement. References 11-13 added
September 2013 Policy formatting and language revised.  Title changed from "Hematopoietic Stem-Cell Transplantation for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma" to "Stem-Cell Transplant (SCT) for Treatment of Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)".
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Stem-Cell Transplant (SCT) for Treatment of Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)