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A long-term durable remission with high-dose therapy and autologous stem cell transplant for stage IVB HIV-associated Hodgkins disease

Gabriel, Iana; Apperley, Janea; Bower, Markb; Chaidos, Aristeidisa; Gazzard, Brianc; Giles, Chrissya; Kew, Andreaa; Nelson, Markc; Kanfer, Eda

doi: 10.1097/QAD.0b013e3282f0e3e5
Research Letters

A 44-year-old man with relapsed HIV-associated stage IV nodular sclerosing Hodgkin's disease underwent high-dose therapy with autologous stem cell transplantation. The transplant was uncomplicated and the patient remains in complete remission at 59 months. Autologous stem cell transplantation is safe in HIV patients and can achieve long-term durable remissions in Hodgkin's disease.

aDepartment of Clinical Haematology, Hammersmith Hospital, London, UK

bDepartment of Clinical Oncology, Chelsea and Westminster Hospital, London, UK

cDepartment of HIV Medicine, Chelsea and Westminster Hospital, Centre for Infections, Health Protection Agency, London, UK.

Received 27 April, 2007

Accepted 27 April, 2007

A 44-year-old man was diagnosed with HIV infection in 1999. He remained well until 2 years later when the patient was diagnosed with stage IVB nodular sclerosing Hodgkin's disease with bone marrow involvement. He was initially treated with six cycles of doxorubicin, bleomycin vinblastine and dacarbazine, and achieved a complete radiological remission. Four months later he re-presented with biopsy-confirmed axillary recurrence.

At relapse, the patient received two cycles of dexamethasone, cytarabine and cisplatinum as salvage chemotherapy, followed by an etoposide/granulocyte colony-stimulating factor (GCSF)-conditioned peripheral blood stem cell mobilization.

He underwent an autologous haematopoietic stem cell transplant (ASCT) in May 2002. The conditioning regimen was LACE: lomustine (cyclohexyl-chloroethyl-nitrosourea) 200 mg/m2 and etoposide 1000 mg/m2 on day −7, cytarabine 2000 mg/m2 on days −5 and −6, and cyclophosphamide 1800 mg/m2 on days −4 to −2. The stem cell dose was 4.06 × 106/kg CD34 cells. Viral load at the time of transplant was 65.0 RNA copies/ml with a CD4 cell count of 479 × 109 cells/l. He remained on HAART (stavudine, lamivudine and efavirenz) during the transplant procedure and received prophylactic azithromycin and septrin throughout.

The transplant procedure was uncomplicated. He developed an episode of sepsis on day 7 after transplant as a result of a coagulase-negative staphyloccocal infection, which responded to intravenous antibiotics. Neutrophil engraftment occurred on day 14 and platelet engraftment on day 18. The patient was discharged home on day 20. The patient remains in complete remission at 59 months post-ASCT. His HIV disease is well controlled, with an undetectable viral load and CD4 cell count of more than 760 × 109 cells/l on HAART (efavirenz, tenofovir and lamivudine).

Information on the role of ASCT in HIV-associated lymphoma is limited. The few published small series have predominantly concentrated on patients with non-Hodgkins lymphoma (NHL). Only a few cases of ACST in HIV-associated Hodgkin's disease have been described. Krishnan et al. [1] described two cases of mixed cellularity Hodgkin's disease transplanted in the first relapse. Both patients entered complete remission and were reported alive in remission at 61 and 56 months. The two patients were mobilized with a cyclophosphamide/GCSF mobilizing regimen. A multi-institutional Italian study reported by Re et al. [2] in 2003 assessed nine out of 10 ASCT patients for HIV-related lymphoma with a short follow-up. The patients were also mobilized using cyclophosphamide with an 80% success rate. Six patients in that study remain alive at a median of 8 months. The histological subtype and length of follow-up of the four Hodgkin's disease patients transplanted were unclear in the final analysis, which did not differentiate between Hodgkin's disease and NHL. More recently, the European Group for Blood and Marrow Transplant Lymphoma Working Party have published in abstract form a series of 44 HIV-associated lymphomas with 23% Hodgkin's disease with a median follow-up of 36.3 months [3]. The overall survival (NHL and Hodgkin's disease) for those with chemosensitive disease in first complete remission at the time of ASCT was 85%. Currently no data are available on the specific outcome of the cases of Hodgkin's disease.

Here, we report that a LACE-conditioned ASCT for HIV-associated Hodgkin's disease can result in long-term complete remission. ASCT is capable of achieving long-term complete remission in HIV nodular sclerosing Hodgkin's disease (intermediate prognosis) as well as in mixed cellularity Hodgkin's disease. Etoposide/GCSF can achieve an adequate cell harvest dose and can be used as an alternative to cyclopshosphamide/GCSF to mobilize peripheral blood stem cells with the concurrent use of antiretroviral agents. This information adds to the slowly emerging data on ASCT in HIV. We concur with the other investigators that durable remissions are achievable in this setting, and that in well-controlled patients HIV status is no barrier to high-dose therapy. HIV infection has, in the era of HAART, become for many sufferers a chronic condition, often managed in the outpatient setting with increased long-term survival. More information is required; however, it is becoming increasingly evident that ASCT results in an improved survival much in the way that it does in the non-HIV setting. We believe that transplant centres currently need to collaborate to review data collectively on ASCT in HIV-associated Hodgkin's disease to try to achieve a greater understanding of the role of ASCT in this setting.

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1. Krishnan A, Molina A, Zaia J, Smith D, Vasquez D, Kogut N, et al. Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas. Blood 2005; 105:874–878.
2. Re A, Cattaneo C, Michieli M, Casari S, Spina M, Rupolo M, et al. High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy. J Clin Oncol 2003; 21:4423–4427.
3. Balsalobre P, Serrano D, Re A, Rosselet A, Conde E, Ribera JM, et al. on Behalf of the EBMT Lymphoma Working Party. Autologous stem cell transplantation (ASCT) in HIV associated lymphoma (HIV-Ly) patients: the EBMT Lymphoma Working Party (EBMT-LWP) experience. In: 33rd EBMT Annual Conference. Lyon, France; 24–28 March 2007. Poster presentation no. 3042.
© 2008 Lippincott Williams & Wilkins, Inc.