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MP 8.01.15 Hematopoietic Stem-Cell Transplantation for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Medical Policy    
Section
Therapy
 
Original Policy Date
7/31/99
Last Review Status/Date
Reviewed with literature search/1:2012
Issue
1:2012
  Return to Medical Policy Index

Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically. 


Description

Hematopoietic Stem-Cell Transplantation
Hematopoietic stem-cell transplantation (SCT) refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in cancer patients who receive bone-marrow-toxic doses of cytotoxic drugs, with or without whole-body radiation therapy. Bone-marrow stem cells may be obtained from the transplant recipient (autologous SCT, auto-SCT) or from a donor (allogeneic SCT, allo-SCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood and placenta shortly after delivery of neonates. Although cord blood is an allogeneic source, the stem cells in it are antigenically “naïve” and thus are associated with a lower incidence of rejection or graft versus host disease. Cord blood is discussed in greater detail in policy No. 7.01.50.

Immunologic compatibility between infused stem cells and the recipient is not an issue in auto-SCT. However, immunologic compatibility between donor and patient is a critical factor for achieving a good outcome of allo-SCT. 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 HLA A, B, and DR loci on each arm of chromosome 6. Depending on the disease being treated, an acceptable donor will match the patient at all or most of the HLA loci. 

Conventional Preparative Conditioning for Hematopoietic Stem-Cell Transplantation (SCT) 

The conventional (“classical”) practice of allogeneic SCT involves administration of cytotoxic agents (e.g., cyclophosphamide, busulfan) with or without total body irradiation at doses sufficient to destroy endogenous hematopoietic capability in the recipient. The beneficial treatment effect in this procedure is due to a combination of initial eradication of malignant cells and subsequent graft-versus-malignancy (GVM) effect that develops after engraftment of allogeneic stem cells within the patient’s bone marrow space. While the slower GVM effect is considered to be the potentially curative component, it may be overwhelmed by extant disease without the use of pretransplant conditioning. However, intense conditioning regimens are limited to patients who are sufficiently fit medically to tolerate substantial adverse effects that include pre-engraftment opportunistic infections secondary to loss of endogenous bone marrow function and organ damage and failure caused by the cytotoxic drugs. Furthermore, in any allogeneic SCT, immune suppressant drugs are required to minimize graft rejection and GVHD, which also increases susceptibility of the patient to opportunistic infections.

The success of autologous SCT is predicated on the ability of cytotoxic chemotherapy with or without radiation to eradicate cancerous cells from the blood and bone marrow. This permits subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic stem cells obtained from the patient prior to undergoing bone marrow ablation. As a consequence, autologous SCT is typically performed as consolidation therapy when the patient’s disease is in complete remission. Patients who undergo autologous SCT are susceptible to chemotherapy-related toxicities and opportunistic infections prior to engraftment, but not GVHD.

Reduced-Intensity Conditioning for Allogeneic Stem-Cell Transplantation (SCT)

Reduced-intensity conditioning (RIC) refers to the pretransplant use of lower doses or less intense regimens of cytotoxic drugs or radiation than are used in conventional full-dose myeloablative conditioning treatments. The goal of RIC is to reduce disease burden, but also to minimize as much as possible associated treatment-related morbidity and non-relapse mortality (NRM) in the period during which the beneficial GVM effect of allogeneic transplantation develops. Although the definition of RIC remains arbitrary, with numerous versions employed, all seek to balance the competing effects of NRM and relapse due to residual disease. RIC regimens can be viewed as a continuum in effects, from nearly totally myeloablative, to minimally myeloablative with lymphoablation, with intensity tailored to specific diseases and patient condition. Patients who undergo RIC with allogeneic SCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to full-donor chimerism, which may be supplemented with donor lymphocyte infusions to eradicate residual malignant cells. For the purposes of this Policy, the term “reduced-intensity conditioning” will refer to all conditioning regimens intended to be non-myeloablative, as opposed to fully myeloablative (conventional) regimens. 

Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (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, while in SLL they are generally confined to lymph nodes. The Revised European-American/WHO 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’s 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 outcomes of treatment are comparable for the 2 diseases. Both low- and intermediate-risk CLL and SLL demonstrate relatively good prognoses with median survivals of 6 to 10 years, while the median survival of high-risk CLL or SLL may be only 2 years (see Policy Guidelines). 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 as a possible curative regimen.

Note: Before the fourth quarter of 1999, this policy (No. 8.01.15) addressed high-dose chemotherapy for a variety of malignancies. In the third quarter of 1999, revision of this policy was initiated, with separate policies being created for each disease entity formerly included in policy No. 8.01.15. Policy Nos. 8.01.17, 8.01.20 through 8.01.32, 8.01.34, and 8.01.35 represent the products of this revision. Original policy No. 8.01.15 was deleted, and high-dose chemotherapy for chronic lymphocytic leukemia and small lymphocytic lymphoma was reassigned the number 8.01.15.


Policy

Autologous hematopoietic stem-cell transplantation is considered investigational to treat chronic lymphocytic leukemia or small lymphocytic lymphoma.

Allogeneic hematopoietic stem-cell transplantation is considered medically necessary to treat chronic lymphocytic leukemia or small cell lymphocytic leukemia in patients with markers of poor-risk disease (see Policy Guidelines and Rationale). Use of a myeloablative or reduced-intensity pretransplant conditioning regimen should be individualized based on factors that include patient age, the presence of comorbidities, and disease burden.


Policy Guidelines

Staging and Prognosis of CLL/SLL

Two scoring systems are used to determine stage and prognosis of patients with CLL/SLL. As outlined in the Table 1, the Rai and Binet staging systems classify patients into 3 risk groups with different prognoses, and are used to make therapeutic decisions.

Table 1. Rai and Binet Classification for CLL/SLL 

Rai
Stage

Risk

Description

Median
Survival
(yr)

Binet
Stage

Description

Median
Survival
(yr)

0

Low

Lymphocytosis

>10

A

3 or fewer lymphoid
areas, normal
hemoglobin and platelets

>10

I

Intermediate

Lymphocytosis plus lymphadenopathy

7-9

B

3 or more lymphoid
areas, normal
hemoglobin and platelets

7

II

Intermediate

Lymphocytosis plus splenomegaly plus/minus lymphadenopathy

7-9

 

 

 

III

High

Lymphocytosis plus anemia plus/minus lymphadenopathy or splenomegaly

1.5-5

C

Any number of lymphoid areas, anemia, thrombocytopenia

5

IV

High

Lymphocytosis plus thrombocytopenia plus/minus anemia, splenomegaly or lymphadenopathy

1.5-5

 

 

 

lymphocytosis = lymphocytes > 15 x 109/L for 4 wks; anemia = hemoglobin < 110 g/L; thrombocytopenia = platelets < 100 x 109/L

Because prognosis of patients varies within the different Rai and Binet classifications, other prognostic markers are used in conjunction with staging to determine clinical management. These are summarized in Table 2, according to availability in clinical centers.

Table 2. Markers of Poor Prognosis in CLL/SLL 

Community Center Specialized Center
Advanced Rai or Binet stage
Male sex
Atypical morphology or CLL/PLL
Peripheral lymphocyte doubling time < 12 mos
CD38+
Elevated beta2-microglobulin level
Diffuse marrow histology
Elevated serum lactate dehydrogenase level
Fludarabine resistance
IgVh wild type
Expression of ZAP-70 protein
del 11q22-q23 (loss of ATM gene)
del 17p13 (loss of p53)
trisomy 12
Elevated serum CD23
Elevated serum tumor necrosis factor-a
Elevated serum thymidine kinase

Reduced-Intensity Conditioning for Allogeneic SCT

Some patients for whom a conventional myeloablative allotransplant could be curative may be considered candidates for RIC allogeneic SCT. These include those whose age (typically older than 60 years) or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status) preclude use of a standard myeloablative conditioning regimen. A patient who relapses following a conventional myeloablative allogeneic SCT could undergo a second myeloablative procedure if a suitable donor is available and his or her medical status would permit it. However, this type of patient would likely undergo RIC prior to a second allogeneic SCT if a complete remission could be re-induced with chemotherapy.

The ideal allogeneic donors are HLA-identical siblings, matched at the HLA-A, B, and DR loci (6 of 6). Related donors mismatched at one locus are also considered suitable donors. A matched, unrelated donor identified through the National Marrow Donor Registry is typically the next option considered. Recently, there has been interest in haploidentical donors, typically a parent or a child of the patient, where usually there is sharing of only 3 of the 6 major histocompatibility antigens. The majority of patients will have such a donor; however, the risk of GVHD and overall morbidity of the procedure may be severe, and experience with these donors is not as extensive as that with matched donors.

In 2003, CPT centralized codes describing allogeneic and autologous hematopoietic stem-cell transplant services to the hematology section (CPT 38204–38242). Not all codes are applicable for each stem-cell transplant procedure. For example, Plans should determine if cryopreservation is performed. A range of codes describes services associated with cryopreservation, storage, and thawing of cells (38208–38215).

CPT 38208 and 38209 describe thawing and washing of cryopreserved cells
CPT 38210–38214 describe certain cell types being depleted
CPT 38215 describes plasma cell concentration


Benefit Application
BlueCard/National Account Issues

Hematopoietic stem-cell transplanation for CLL is available at a limited number of institutions. Therefore, this therapy may be identified by a request for an out-of-network referral.


Rationale

This policy initially was based on two TEC Assessments, one from 1999 on autologous hematopoietic stem-cell transplantation (auto-SCT) for CLL or SLL (1); the other from 2002 on allogeneic stem-cell transplantation (allo-SCT) to treat CLL or SLL. (2) Both documents indicated that in the absence of randomized trials, existing data were insufficient to permit scientific conclusions regarding the use of either procedure, limited by interstudy 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 TEC in 2002 to analyze allo-SCT 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 July 2008 found no randomized trials of hematopoietic SCT 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 autologous 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 HSCT

A systematic review of autologous HSCT for CLL or SLL included 9 studies (total n=361, 292 of which were transplanted) identified from a search of MEDLINE databases from 1966 to September 2006. (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 autologous 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 that may progress to frank acute myelogenous leukemia has been reported in 5-12% of patients in some studies of autologous 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 autologous 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 autologous HSCT outlined above are congruent with results of a Phase III randomized trial published in 2010 that compared autologous 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 NRM between groups, 4% in the autologous 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 autologous 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 autologous 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 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 autologous HSCT in this setting may prolong time to progression compared with observation, but that because OS is not improved, autologous HSCT remains investigational for CLL/SLL patients. (12, 13)

Allogeneic HSCT

Given that autologous HSCT based on myeloablative conditioning regimens has not been demonstrated to be a curative treatment of CLL/SLL, alternative modalities have been sought. Allogeneic HSCT has been under investigation for the past 2 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. As indicated in the Description section of this policy, allogeneic HSCT may include use of myeloablative or reduced-intensity pretransplant conditioning regimens.

Data compiled in numerous review articles suggest that myeloablative allogeneic 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 condidtioning (RIC) regimens has extended the use of allogeneic 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 allogeneic 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 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 an 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 autologous 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.

Summary

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/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 allogeneic 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) Some of these are outlined in Table 2 in the Policy Guidelines section above.

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 overall survival (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.

Clinical Guidelines

European Group for Blood and Marrow Transplantation (EBMT)

In June 2005, the EBMT convened a consensus panel to identify situations in which allogeneic 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 4 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 allogeneic HSCT in CLL?
  • Which prognostic risk level justifies allogeneic 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 allogeneic 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 allogeneic HSCT for poor-risk CLL. While allogeneic 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.

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)

National Comprehensive Cancer Network (NCCN) Guidelines

Current NCCN Guidelines for non-Hodgkin’s lymphoma do not include autologous HSCT as a therapeutic option in CLL or SLL. (26) NCCN indicates that allogeneic 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.

Physician Specialty Society and Academic Medical Center Input

In response to requests, input was received from 1 specialty medical center reviewer, 1 academic medical center reviewer, and 2 Blue Distinction Center reviewers while this policy was under review. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. Three of 4 reviewers agree that allogeneic HSCT was of value in patients who have poor-risk CLL (see Policy Guidelines) and that this procedure should be medically necessary in this setting. However, the reviewers indicate that the specific approach (e.g., RIC versus myeloablative conditioning) should be individualized based upon criteria such as age and health status. All reviewers concur with the policy statement that autologous HSCT is investigational.

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

In December 2011, the NCI Clinical Trials Database indicated 7 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, available online at: http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=7157492

References:

  1. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). High-dose chemotherapy with autologous stem cell support for chronic lymphocytic leukemia/small lymphocytic lymphoma. TEC Assessments 1999; Volume 14, Tab 20
  2. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). High-dose chemotherapy plus allogeneic stem cells to treat chronic lymphocytic leukemia or small lymphocytic lymphoma. TEC Assessments 2002; Volume 17, Tab 4
  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.  
  8. Gribben JG. Role of allogeneic hematopoietic stem-cell transplantation in chronic lymphocytic leukemia. J Clin Oncol 2008; 26(30):4864-5.
  9. Kharfan-Dabaja MA, Anasetti C, Santos ES. Hematopoietic cell transplantation for chronic lymphocytic leukemia: an evolving concept. Biol Blood Marrow Transplant 2007; 13(4):373-85.
  10. 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.
  11. 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.
  12. 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.
  13. Montserrat E, Gribben JG. Autografting CLL: the game is over! Blood 2011; 117(23):6057-8.
  14. 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.
  15. Delgado J, Milligan DW, Dreger P. Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for prime time? Blood 2009; 114(13):2581-8.
  16. Dreger P. Allotransplantation for chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2009:602-9.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. Kipps TJ. Chronic lymphocytic leukemia: advances in assessing prognosis and therapy. American Society of Clinical Oncology (ASCO) Education Book 2009:385-93.
  25. 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.
  26. 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.
  27. National Comprehensive Cancer Network. Non-Hodgkin's Lymphoma. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. V.4.2011. 

Codes

Number

Description

CPT  38204  Management of recipient hematopoietic cell donor search and cell acquisition 
  38205  Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection, allogeneic 
  38206  Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection, autologous 
  38208  Transplant preparation of hematopoietic progenitor cells; thawing of previously frozen harvest, without washing
  38209  ;thawing of previously frozen harvest, with washing
  38210  ;specific cell depletion with harvest, T-cell depletion 
  38211  ;tumor cell depletion 
  38212  ;red blood cell removal 
  38213  ;platelet depletion 
  38214  'plasma (volume) depletion 
  38215  ;cell concentration in plasma, mononuclear, or buffy coat layer 
  38220  Bone marrow, aspiration only 
  38221  ;biopsy, needle or trocar 
  38240  Bone marrow or blood-derived peripheral stem-cell transplantation; allogeneic 
  38241  Bone marrow or blood-derived peripheral stem-cell transplantation; autologous 
  38242  ;allogeneic donor lymphocyte infusions 
  38243 Hematopoietic progenitor cell (HPC); HPC boost
ICD-9 Procedure  41.01  Autologous bone marrow transplant without purging
  41.02  Allogeneic bone marrow transplant with purging 
  41.03  Allogeneic bone marrow transplant without purging 
  41.04  Autologous hematopoietic stem-cell transplant without purging
  41.05  Allogeneic hematopoietic stem-cell transplant without purging
  41.06 Cord blood stem cell transplant
  41.07 Autologous hematopoietic stem cell transplant with purging
  41.08 Allogeneic hematopoietc stem cell transplant with purging
  41.09 Autologous bone marrow transplant with purging
  41.91  Aspiration of bone marrow from donor for transplant 
  99.79  Other therapeutic apheresis (includes harvest of stem cells) 
ICD-9 Diagnosis  204.10–204.11  Chronic lymphocytic leukemia code range 
HCPCS  G0265  Cryopreservation, freezing and storage of cells for therapeutic use, each cell line 
  G0266  Thawing and expansion of frozen cells for therapeutic use, each cell line 
  G0267  Bone marrow or peripheral stem-cell harvest, modification or treatment to eliminate cell type(s) (e.g., T cells, metastatic carcinoma) 
  Q0083, Q0084, Q0085  Chemotherapy administration code range 
  J9000, J9001, J9010, J9015, J9017, J9020, J9025, J9027, J9031, J9035, J9040, J9041, J9045, J9050, J9055, J9060, J9062, J9065, J9070, J9080, J9090, J9091, J9092, J9093, J9094, J9095, J9096, J9097, J9098, J9100, J9110, J9120, J9130, J9140, J9150, J9151, J9160, J9165, J9170, J9175, J9178, J9181, J9182, J9185, J9190, J9200, J9201, J9202, J9206, J9208, J9209, J9211, J9212, J9213, J9214, J9215, J9216, J9217, J9218, J9219, J9225, J9226, J9230, J9245, J9250, J9260, J9261, J9263, J9264, J9265, J9266, J9268, J9270, J9280, J9290, J9291, J9293, J9300, J9303, J9305, J9310, J9320, J9340, J9350, J9355, J9357, J9360, J9370, J9375, J9380, J9395, J9600, J9999  Chemotherapy drug code range 
  S2140 Cord blood harvesting for transplantation, allogeneic
  S2142 Cord blood-derived stem cell transplantation, allogeneic
  S2150  Bone marrow or blood-derived peripheral stem-cell harvesting and transplantation, allogeneic or autologous, including pheresis, high-dose chemotherapy, and the number of days of post-transplant care in the global definition (including drugs; hospitalization; medical, surgical, diagnostic, and emergency services) 
ICD-10-CM (effective 10/1/13)    Chronic lymphocytic leukemia of B-cell type code range
ICD-10-PCS (effective 10/1/13)    ICD-10-PCS codes are only used for inpatient services.
   30250G0, 30250X0,
30250Y0
Administration, circulatory, transfusion, peripheral artery, open, autologous, code by substance (bone marrow, cord blood or stem cells, hematopoietic)
   30250G1, 30250X1,
30250Y1
Administration, circulatory, transfusion, peripheral artery, open, nonautologous, code by substance (bone marrow, cord blood or stem cells, hematopoietic)
   30253G0, 30253X0,
30253Y0
Administration, circulatory, transfusion, peripheral artery, percutaneous, autologous, code by substance (bone marrow, cord blood or stem cells, hematopoietic)
   30253G1, 30253X1,
30253Y1
Administration, circulatory, transfusion, peripheral artery, percutaneous, nonautologous, code by substance (bone marrow, cord blood or stem cells, hematopoietic)
   6A550ZT, 6A550ZV Extracorporeal Therapies, pheresis, circulatory, single, code by substance (cord blood, or stem cells, hematopoietic)
   6A551ZT, 6A551ZV Extracorporeal Therapies, pheresis, circulatory, multiple, code by substance (cord blood, or stem cells, hematopoietic)
Type of Service  Therapy 
Place of Service  Inpatient/Outpatient 

 


Index

Chronic Lymphocytic Leukemia, High-Dose Chemotherapy
High-Dose Chemotherapy, Chronic Lymphocytic Leukemia  


Policy History

Date Action Reason
07/31/99 Add to Therapy section New policy
01/30/98 Replace policy Reviewed with changes; new indications
04/01/98 Replace policy Policy reviewed but unchanged; 1998 TEC Assessment referenced
01/27/99 Replace policy Policy reviewed but unchanged; 1999 TEC Assessment referenced
12/01/99 Replace policy Policy revised with many of the original components addressed in new policies (8.01.17–8.01.31). Policy now onlyaddressesacute lymphoblastic leukemia, chronic lymphocytic leukemia, pediatric solid tumors, and germ cell tumors. Policy statements are unchanged
04/30/00 Replace policy Policy reformatted; policy statement unchanged
05/15/02 Replace policy Policy reviewed but unchanged; 2002 TEC Assessment referenced
12/18/02 Replace policy Update CPT codes only
07/15/04 Replace policy Policy reviewed with literature search; policy statement unchanged
05/23/05 Replace policy Policy reviewed with literature search; policy statement unchanged. Reference numbers 7 and 8 added
7/20/06 Replace policy Policy reviewed with literature search; policy statement unchanged
09/18/07 Replace Policy Policy reviewed with literature search; references 9–12 added. Policy statement unchanged.
09/11/08 Replace policy  Policy reviewed with literature search and revised extensively; “high-dose chemotherapy” removed from policy title and policy statements. “Stem-cell transplantation” (SCT) now used instead of “stem-cell support” (SCS) in policy and policy statements. Intent of current policy statements unchanged. References 5-9 and 11 added; reference 12 updated 
01/14/10 Replace policy Policy reviewed with literature search and revised extensively; clinical input reviewed. Policy statement regarding allogeneic transplant in patients with markers of poor-risk disease changed; now may be considered medically necessary. New references 11-18 added; reference 21 updated
01/13/11 Replace policy Policy reviewed with literature search; no change to policy statement. References 10 and 19 added
1/12/12 replace policy Policy reviewed with literature search; no change to policy statement. References 11-13 added