BlueCross and BlueShield of Montana Medical Policy/Codes
Hematopoietic Stem-Cell Transplantation for Hodgkin Lymphoma
Chapter: Transplant
Current Effective Date: December 27, 2013
Original Effective Date: July 09, 2008
Publish Date: September 27, 2013
Revised Dates: March 1, 2010; April 2, 2012; September 13, 2013

Hodgkin Lymphoma (HL)

HL is a relatively uncommon B-cell lymphoma.  In 2008, an estimated 8,220 new diagnoses and 1,350 deaths will occur in the U.S.  The disease has a bimodal distribution, with most patients diagnosed between the ages of 15 and 30 years, with a second peak in adults aged 55 and older.

The World Health Organization (WHO) classification divides HL into two main types:

  1. “Classical” HL (CHL):
    • Nodular sclerosis,
    • Mixed cellularity,
    • Lymphocyte-depleted, and
    • Lymphocyte-rich.
  2. Nodular Lymphocyte-Predominant (NLPHL)

In Western countries, CHL accounts for 95% of cases of HL and NLPHL only 5%.  Classic HL is characterized by the presence of neoplastic Reed-Sternberg cells in a background of numerous non-neoplastic inflammatory cells.  NLPHL lacks Reed-Sternberg cells, but is characterized by the presence of lymphocytic and histiocytic cells termed “popcorn cells”.

The following staging system for HL recognizes the fact that the disease is thought to typically arise in a single lymph node and spread to contiguous lymph nodes with eventual involvement of extranodal sites.  The staging system attempts to distinguish patients with localized HL who can be treated with extended field radiation from those who require systemic chemotherapy.

Staging for Hodgkin Lymphoma (HL)

Staging for HL is based on the Ann Arbor staging system.  Each stage is subdivided into A and B categories. “A” indicates no systemic symptoms are present and “B” indicates the presence of systemic symptoms including unexplained weight loss of more than 10% of body weight, unexplained fevers or drenching night sweats.  

Stage I

Involvement of a single lymph node region (I) or localized involvement of a single extralymphatic organ or site (IE).

Stage II

Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ or site and its regional lymph node(s) with or without involvement of other lymph node regions on the same side of the diaphragm (IIE).  The number of lymph node regions involved should be indicated by a subscript (e.g., II2)

Stage III

Involvement of lymph node regions or structures on both sides of the diaphragm.  These patients are further subdivided as follows:

  • III-1: disease limited to spleen or upper abdomen,
  • III-2: periaortic or pelvic node involvement.

Stage IV

Disseminated (multifocal) involvement of one or more extralymphatic organs, with or without associated lymph node involvement, or isolated extralymphatic organ involvement with distant (non regional) nodal involvement.

Patients with HL are generally classified into three groups:

  • early-stage favorable (stage I–II with no B symptoms or large mediastinal lymphadenopathy),
  • early-stage unfavorable (stage I–II with large mediastinal mass, with or without B symptoms; stage IB–IIB with bulky disease), and
  • advanced-stage disease (stage III–IV).

Patients with non bulky stage IA or IIA disease are considered to have clinical early stage disease. These patients are candidates for chemotherapy, combined modality therapy, or radiation therapy alone.  Patients with obvious stage III or IV disease, bulky disease (defined as a 10-cm mass or mediastinal disease with a transverse diameter exceeding 33% of the transthoracic diameter), or the presence of B symptoms will require combination chemotherapy with or without additional radiation therapy. 

HL is highly responsive to conventional chemotherapy, and up to 80% of newly diagnosed patients can be cured with combination chemotherapy and/or radiation therapy.  Patients who prove refractory or who relapse after first-line therapy have a significantly worse prognosis. Primary refractory HL is defined as disease regression of less than 50% after 4–6 cycles of anthracycline-containing chemotherapy, disease progression during induction therapy, or progression within 90 days after the completion of first-line treatment. 

In patients with relapse, the results of salvage therapy vary depending upon a number of prognostic factors, as follows: the length of the initial remission, with approximately 70% of patients with late first relapse being salvaged by autoSCT, but not more than 40% with early first relapse (early and late relapse being defined as less or more than 12 months from the time of remission, respectively).  Other prognostic factors include stage at recurrence and severity of anemia at the time of relapse.  Of patients with refractory HL, only 20–35% may achieve long-term survival with autoSCT.


Each benefit plan or contract defines which services are covered, which are excluded, and which are subject to dollar caps or other limits.  Members and their providers have the responsibility for consulting the member's benefit plan 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 or contract, the benefit plan or contract will govern.


Coverage for evaluation of 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 Hodgkin Lymphoma (HL) is identified in the grid below.


May be considered medically necessary in patients with primary refractory or relapsed HL. 

Is considered experimental, investigational and unproven to treat HL relapsing after an autoSCT (autologous stem cell transplant) used to treat primary refractory or relapsed disease.



May be considered medically necessary in patients with primary refractory or relapsed HL. 

Is considered experimental, investigational and unproven including, but not limited to, initial or upfront therapy or for consolidation of patients in first complete remission.

Tandem or Triple Stem-Cell Transplant

Is considered experimental, investigational and unproven. 

Donor Leukocyte Infusion

Is considered experimental, investigational and unproven. 


The quality of life after high-dose chemotherapy (HDC) followed by hematopoietic stem-cell (HSC) (i.e., blood or marrow) transplant is of utmost importance.  In aplastic anemia and malignancies, there is the expectation of improved status after HDC and HSC.  Conversely, quality of life outcomes (measured by growth, skeletal development dysfunction, and neuropsychological) for patients with storage diseases is gradually being defined.  Because of these long-term problems, non-malignant or maldevelopment indications for HDC and HSCs should not be reviewed with criteria similar to that for malignancies.

This policy is based on a 1987 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment that focused on high-dose therapy plus autologous stem-cell support and a 1990 BCBSA TEC Assessment that focused on high-dose therapy plus allogeneic stem-cell support.  Each report concluded that data showed longer survival of patients with relapsed disease after transplants than after standard therapy.

A 2000 BCBSA TEC Assessment focused on HDC and myeloablative allogeneic stem-cell support after a prior failed course of high-dose chemotherapy and autologous stem-cell support as treatment for various malignancies including Hodgkin’s disease.  The TEC Assessment found that data were inadequate to permit conclusions about outcomes of this treatment strategy.

The following data reflects the most current literature and treatment strategies, including the results of the relatively recent uses of RIC (reduced-intensity conditioning)-alloSCTs.

Autologous Stem Cell Transplant (autoSCT) for Hodgkin Lymphoma (HL)

AutoSCT is widely considered the therapy of choice for relapsed and refractory HL.  Two randomized, controlled studies showed benefit in using autoSCT in these patients:

  • The British National Lymphoma Investigation (BNLI) study was the first to show a progression-free survival benefit with autoSCT over conventional chemotherapy in relapsed or refractory HL patients.  Forty patients with relapsed or refractory HL were given chemotherapy without transplant (n=20) or autologous transplant after high-dose chemotherapy (n=20).  A significantly better event-free survival at three years of 53% versus 10% was reported in the patients who underwent transplant versus the group that did not.
  • Subsequently, these findings were confirmed in a larger trial by the GHSG (German Hodgkin Study Group) and European Group for Blood and Marrow Transplantation (EBMT).  Patients relapsing after initial chemotherapy were randomized to chemotherapy without transplant or to autoSCT.  In the final analysis of 144 patients, freedom from treatment failure at three years was 55% in the transplanted group, versus 34% in the non transplanted group.  This benefit was maintained in subgroup analysis, regardless of early or late relapse and the results were confirmed in follow-up data at seven years. 

Several large retrospective studies have reported event-free survival rates ranging from 25–60%, with overall survival rates from 35–66%, showing that disease status before autoSCT was the most important prognostic factor for the final outcome.

Limited treatment options exist for patients who relapse following an autoSCT, and include single-agent palliative chemotherapy or occasionally, localized radiation therapy.  When a further remission may be attained with conventional-dose chemotherapy, it is rarely durable, with a median overall survival of less than one year.  There is limited experience with second autoSCTs, and treatment-related mortality is high (25–40%). 

Allogeneic Stem Cell Transplant (alloSCT) for Hodgkin Lymphoma (HL)

The application of alloSCT to the treatment of patients with HL initially appeared limited due to a procedure-related mortality rate of approximately 50% associated with the myeloablative conditioning regimen.  A small number of studies have investigated the role of RIC (reduced-intensity conditioning)-alloSCT in refractory and relapsed HL, and the preliminary results have been encouraging, as detailed below.  To date, most of the RIC-alloSCTs have been performed in patients who have failed a previous autoSCT for primary relapsed/refractory HL.

Peggs et al. investigated outcomes with RIC-alloSCT and T-cell depletion in multiply relapsed patients.  Forty-nine patients were enrolled, 90% of whom had failed a previous autologous transplant.  Primary study endpoints were engraftment, toxicity, non-relapse-related mortality and graft-versus-host-disease incidence.  All patients achieved engraftment.  Thirty-one patients had an HLA-matched donor and 18 an unrelated donor.  The cumulative incidence of non-relapse-related mortality was 4.1% at 100 days post-transplant and 16.3% at 730 days post-transplant. Patients with unrelated donors had a significantly higher non-relapse-related mortality, 34% versus 7% at 730 days.  Projected four year overall survival and progression-free survival were 56% and 39%, respectively.

Alvarez et al. reported the results of a Spanish Cooperative Protocol using RIC/alloSCT in 40 patients with relapsed or refractory HL.  Seventy-three percent of patients had failed a previous autoSCT.  Thirty-eight patients received hematopoietic cells from an HLA-identical sibling.  One-year treatment-related mortality was 25%.  Overall and progression-free survival was 48 and 32%, at two years, respectively.  For patients who had failed a previous autoSCT, two year overall and progression-free survival was 75 and 70% in the subset that relapsed more than 12 months after autoSCT.

Todisco et al. evaluated the efficacy of RIC-alloSCT in 14 patients with refractory or progressive HL after high-dose chemotherapy (HDC) and autoSCT.  All of the patients had received at least one prior course of HDC, and 50% had undergone two previous.  The median time from the first and second courses of HDC and the RIC-alloSCT was 15 and eight months, respectively (range 2–34 and 2–31 months).  With a median follow-up of 21 months post RIC-alloSCT (range 3–74 months), 10 of the 14 patients were alive.  Estimated overall survival at one and two years was 93% and 73%, respectively, for the entire population, 83% and 44%, respectively, for patients with chemo resistant disease, and 100% for those with chemo sensitive disease.

No randomized trial has been found that compared autoSCT to alloSCT prospectively. 

In summary, the studies using RIC-alloSCT in relapsed/refractory HL are characterized by small numbers of patients, disparate preparative and graft-versus-host disease prophylaxis regimens, and varying lengths of follow-up.  Nonetheless, they demonstrate reduced non-relapse mortality and some suggest a graft-versus-HL effect with favorable disease control in these poor-prognosis patients.  The results seem to be more favorable in patients with chemo sensitive disease, with related donors, and in the subset of patient who have undergone a previous autoSCT; those who experience disease relapse more than 12 months after transplant.

Prospective, larger, comparative studies are needed to clarify the role RIC-alloSCT will play in the treatment of patients with HL.

Autologous SCT for front-line therapy of Hodgkin Disease (HD)

A study published by Federico and colleagues concluded that HDC with autoSCT offered no benefit in outcomes over conventional chemotherapy in front-line therapy for advanced Hodgkin lymphoma patients.  This supports the above policy statement indicating HDC as initial or upfront therapy is investigational.

NCCN Guidelines and PDQ® Physician Data Query Database

The 2006 National Comprehensive Cancer Network (NCCN) guidelines on HL recommend HDC with autoSCT for relapsed or refractory disease consistent with this policy.  However, the NCCN guidelines are silent on the use of alloSCT.  The NCCN guidelines also specifically indicate that “up-front” HDC is not indicated, citing evidence that this approach offers no benefit over conventional therapy, as noted here. 

The 2008 NCCN guidelines state that autoSCT is the best option for patients with HL that is incurable with primary treatment, even though it does not improve overall survival.  The 2008 NCCN guidelines state that allogeneic transplant is an option in select patients with progressive or relapsed disease.

The National Cancer Institute’s PDQ database identified two active phase III randomized studies of SCT which include patients with HL:

  • Phase II/III study of standard and novel conditioning therapy and allogeneic blood or marrow transplantation in patients with severe aplastic anemia or hematologic malignancy (Protocol IDs RPCI-RP-9815, NCT00003816, NCI-V99-1527);
  • Phase III randomized study of nonmyeloablative conditioning comprising low-dose total-body irradiation with versus without fludarabine followed by HLA-matched related allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies at low or moderate risk for graft rejection (Protocol IDs FHCRC-1813.00, NCT00075478).


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, 201.00, 201.01, 201.02, 201.03, 201.04, 201.05, 201.06, 201.07, 201.08, 201.10, 201.11, 201.12, 201.13, 201.14, 201.15, 201.16, 201.17, 201.18, 201.20, 201.21, 201.22, 201.23, 201.24, 201.25, 201.26, 201.27, 201.28, 201.40, 201.41, 201.42, 201.43, 201.44, 201.45, 201.46, 201.47, 201.48, 201.50, 201.51, 201.52, 201.53, 201.54, 201.55, 201.56, 201.57, 201.58, 201.60, 201.61, 201.62, 201.63, 201.64, 201.65, 201.66, 201.67, 201.68, 201.70, 201.71, 201.72, 201.73, 201.74, 201.75, 201.76, 201.77, 201.78, 201.90, 201.91, 201.92, 201.93, 201.94, 201.95, 201.96, 201.97, 201.98  

ICD-10 Codes
C56.0-C56.9, 30243G0, 30243X0, 30243Y0, 30243G1, 30243X1, 30243Y1, 07DQ0ZZ, 07DQ3ZZ, 07DR0ZZ, 07DR3ZZ, 07DS0ZZ, 07DS3ZZ 
Procedural Codes: 38204, 38205, 38206, 38207, 38208, 38209, 38210, 38211, 38212, 38213, 38214, 38215, 38230, 38240, 86812 - 86822, Q0083 - Q0085, J9000 - J9999, G0265, G0266, G0267, S2140, S2142, S2150
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  2. Allogeneic Bone Marrow Transplantation (BMT) in the Treatment of Hodgkin’s Disease (Lymphoma) and Non-Hodgkin’s Lymphoma. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center (1990 August):178-211.
  3. Linch, D.C., Winfield, D., et al. Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin’s disease: results of a BNLI randomized trial. Lancet (1993) 341(8852):1051-4.
  4. Harris, N.L., Jaffe, E.S., et al. The World Health Organization Classification of Hematological Malignancies Report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November (1997) Modern Pathology 13:193-207.
  5. Salvage HDC/AlloSCS for Relapse or Incomplete Remission Following HDC/AuSCS for Hematologic Malignancies. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center (2000 December) Tab 9.
  6. Nagler, A., Slavin, S., et al. Allogeneic peripheral blood stem cell transplantation using a fludarabine-based low intensity conditioning regimen for malignant lymphoma. Bone Marrow Transplantation (2000 May) 25(10):1021-8.
  7. Eghbali, H., Soubeyran, P., et al. Current treatment of Hodgkin’s disease.  Critical Reviews in Oncology/Hematology (2000 July) 35(1):49-73.
  8. Anderlini, P., Giralt, S., et al. Allogeneic stem cell transplantation with fludarabine-based, less intensive conditioning regimens as adoptive immunotherapy in advanced Hodgkin’s disease. Bone Marrow Transplantation (2000 September) 26(6):615-20.
  9. Hale, G.A. and G.L. Phillips. Allogeneic stem cell transplantation for the non-Hodgkin’s lymphomas and Hodgkin’s disease. Cancer Treatment Reviews (2000 December) 26(6):411-27.
  10. Brandt, L., Kimby, E., et al. A systematic overview of chemotherapy effects in Hodgkin’s disease.  ACTA Oncologica (2001) 40(2-3): 185-97.
  11. Mink, S.A. and J.O. Armitage. High-dose therapy in lymphomas: A review of the current status of allogeneic and autologous stem cell transplantation in Hodgkin’s disease and non-Hodgkin’s lymphoma. Oncologist (2001) 6(3):247-56.
  12. Lazarus, H.M., Loberiza, F.R., et al. Autotransplants for Hodgkin’s disease in first relapse or second remission: A report from the autologous blood and marrow transplant registry (AMBTR). Bone Marrow Transplantation (2001 February) 27(4):387-96.
  13. Bonfante, V., Viviani, S., et al. High-dose ifosfamide and vinorelbine as salvage therapy for relapsed or refractory Hodgkin’s disease. European Journal of Haematology Supplement (2001 July) (64):51-5.
  14. Bertz, H., Illerhaus, G., et al. Allogeneic hematopoietic stem-cell transplantation for patients with relapsed or refractory lymphomas: Comparison of high-dose conventional conditioning versus fludarabine-based reduced-intensity regimens. (2002 January) 13(1):135-9.
  15. Josting, A., Franklin, J., et al. New prognostic score based on treatment outcome of patients with relapsed Hodgkin’s lymphoma registered in the database of the German Hodgkin’s lymphoma study group. Journal of Clinical Oncology (2002 January 1) 20(1):221-30.
  16. Anselmo, A.P., Cavalieri, E., et al. Dose intensification with autologous stem cell transplantation in relapsed and resistant Hodgkin’s disease. Haematologica (2002 May) 87(5):507-11.
  17. Lin, T.S., Avalos, B.R., et al. Second autologous stem cell transplant for multiple relapsed Hodgkin’s disease. Bone Marrow Transplantation (2002 May) 29(9):763-7.
  18. Josting, A., Rudolph, C., et al. Time-intensified dexamethasone/cisplatin/cytarabine: An effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin’s disease.  Annals of Oncology (2002 October) 13(10):1628-35.
  19. Schmitz, N., Pfistner, B., et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomized trial. Lancet (2002) 359(9323):2065-71.
  20. Federico, M., Bellei, M., et al. High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front-line therapy. Journal of Clinical Oncology (2003) 21(12):2320-5.
  21. Zinzani, P.L., Tani, M., et al. High-dose therapy with autologous transplantation for Hodgkin’s disease: The bologna experience. Haematologica (2003 May) 88(5):522-8.
  22. Gutierrez-Delgado, F., Holmberg, L., et al. Autologous stem cell transplantation for Hodgkin’s disease: Busulfan, melphalan, and thiotepa compared to a radiation-based regimen. Bone Marrow Transplantation (2003 August) 32(3):279-85.
  23. Schmitz, N., Sureda, A., et al. Allogeneic transplantation of hematopoietic stem cells after nonmyeloablative conditioning for Hodgkin’s disease: indications and results. Seminars in Oncology (2004) 31(1):27-32.
  24. Peggs, K.S., Hunter, A., et al. Clinical evidence of a graft-versus-Hodgkin’s-lymphoma effect after reduced-intensity allogeneic transplantation. Lancet (2005) 365(9475):1934-41.
  25. Donor Leukocyte Infusion for Hematologic Malignancies that Relapse after Allogeneic Stem Cell Transplant. BCBSA Medical Policy Reference Manual (2005 September) Medicine: 2.03.03.
  26. Hodgkin Disease/Lymphoma. Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network. V.1.2006. Available at .
  27. Alvarez, I., Sureda, A., et al. Non-myeloablative stem cell transplantation is an effective therapy for refractory or relapsed Hodgkin’s lymphoma: results of a Spanish prospective cooperative protocol. Biology Blood Marrow Transplant (2006) 12(2):172-83.
  28. Schmitz, N., Dreger, P., et al. Allogeneic transplantation in lymphoma: current status. Haematologica (2007) 92(11):1533-48.
  29. Seftel, M., Rubinger, M. The role of hematopoietic stem cell transplantation in advanced Hodgkin lymphoma. Transfusion and Apheresis Science (2007) 37(1):49-56.
  30. Murphy, F., Sirohi, B., et al. Stem cell transplantation in Hodgkin lymphoma. Expert Review of Anticancer Therapy (2007) 7(3):297-306.
  31. Todisco, E., Castagna, L., et al. Reduced-intensity allogeneic transplantation in patients with refractory or progressive Hodgkin’s disease after high-dose chemotherapy and autologous stem cell infusion. European Journal of Haematology (2007) 78(4):322-9.
  32. David, K.A., Mauro, L., et al. Relapsed and refractory Hodgkin lymphoma: Transplantation strategies and novel therapeutic options. Current Treatment Options in Oncology (2007) 8(5):352-74.
  33. Hodgkin Disease/Lymphoma. Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network. V.2.2008. Available online . Accessed June 2008.
  34. Physician Data Query. Adult Hodgkin lymphoma treatment. Modified 04/29/2008. Available online at . Accessed June 2008.
  35. Brice, P. Managing relapsed and refractory Hodgkin lymphoma. British Journal of Haematology (2008) 141(1):3-13.
  36. Hematopoietic Stem-Cell Transplantation for Hodgkin Lymphoma. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2008 June) Therapy 8.01.29
April 2012  Name change from: Transplant: High-Dose Chemotherapy and Hematopoietic Stem-Cell Support to Treat Hodgkin's and Non-Hodgkin's Lymphomas to Hematopoietic Stem-Cell Transplantation for Non-Hodgkin Lymphomas. Divided policy into Hodgkin's and Non-Hodgkin's Lymphoma. updated rationale, references, and policy statements to reflect specific policy.
September 2013 Policy formatting and language revised.  Title changed from "Hematopoietic Stem-Cell Transplantation for Hodgkin Lymphoma" to "Stem-Cell Transplant for Hodgkin Lymphoma".  Removed tandem autologous and reduced-ntensity allogeneic HSCT criteria from the medically necessary statement.
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Hematopoietic Stem-Cell Transplantation for Hodgkin Lymphoma