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Early consolidation with high-dose therapy and autologous stem cell transplantation is a feasible and effective treatment option in HIV-associated non-Hodgkin lymphoma at high risk

Bone Marrow Transplantation volume 53, pages 228–230 (2018)Cite this article

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HIV-infected patients with high risk non-Hodgkin lymphoma (NHL), identified by the International Prognostic Index (IPI),1, 2 have a sub-optimal outcome if treated with standard chemotherapy. In the combination antiretroviral therapy (cART) era, in a randomised trial, the CR rate with CHOP+Rituximab was 46.6% in patients with aa-IPI 2–3.3 Moreover, the 2-year overall survival (OS) of patients with IPI >1 was 50% in a phase II study4 and 49% in patients with aa-IPI 3, in a pooled analysis of 1546 patients, during the more recent time period.5 The use of high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) has shown clinical efficacy, acceptable toxicity6, 7 and an unexpectedly low relapse rate,8, 9, 10 in refractory/relapsed HIV-associated NHL (HIV-NHL). To evaluate the feasibility and efficacy of HDT in the frontline treatment of prognostically unfavourable HIV-NHL, we conducted a prospective multicenter study of ASCT as early consolidation after standard induction therapy, in patients classified at IPI high or high–intermediate risk. This trial is registered to www.ClinicalTrials.gov as NCT01045889.

HIV-infected patients with aggressive NHL, including diffuse large B-cell lymphoma, plasmablastic and anaplastic lymphoma, previously untreated, were eligible if they had an aa-IPI classification of 2 or 3, age 18–60 years and CD4 count higher than 50 cells/μL (Supplementary Table S1). All patients had to be receiving cART or starting cART at study entry. The Institutional Review Board of each partecipating center approved the protocol and informed consent was obtained from each patients in accordance to the Declaration of Helsinki. Patients received CHOP-21 (CHOP-14 was allowed in plasmablastic lymphoma), plus Rituximab in CD20+ lymphoma, as induction therapy, with intrathecal methotrexate prophylaxis. After four courses, patients with CR or PR proceeded with two other courses and cyclophosphamide 4 g/m2 plus G-CSF 10 μg/kg/day to collect stem cells (SCs), whereas patients with less than PR could receive salvage chemotherapy (ESHAP) before SC collection. All responding patients received HDT, according to BEAM conditioning regimen.7 cART was maintained throughout the entire program. The primary end point for the trial was 2-year OS. We assumed an OS of 70% at 2 years, significantly >50%, which is expected from the standard treatment with CHOP±Rituximab in this patient population.4 Using the optimal two-stage design for phase II clinical trials, the number of patients for the first phase was 15. If at least 9/15 patients would be alive at 2 years, the study will continue until the enrollment of 43 total patients. The first step was successfully achieved. From January 2007 to January 2015, 27 patients were enrolled. The principal investigator in accordance with the Institutional Review Board decided to close the recruitment in May 2015, due to the slow enrolment, when 27 patients had been enrolled and the median follow-up exceeded 4 years.

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Acknowledgements

Author contributions

AR and GR contributed to study design, data analysis and interpretation, writing and approval of manuscript. AR and CS performed statistical analysis. GG, MR, AL, AB, AML, PT, CC, SC, CB, MS, BA, LV, MM, CA, PFL and UT contributed to patient registration and treatment, data collection, data interpretation and approval of the manuscript. AR had full access to the data and final responsibility for the decision to submit for publication.

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Authors and Affiliations

  1. Department of Hematology, Spedali Civili, Brescia, Italy

    A Re, P Tozzi, C Cattaneo & G Rossi

  2. Department of Hematology, Ospedali Riuniti Umberto I, Ancona, Italy

    G Gini & C Bocci

  3. Unit of High Dose Chemotherapy and Cellular Therapies, CRO, Aviano, Italy

    M Rupolo & M Michieli

  4. Department of Hematology, AOSS Antonio e Biagio e C. Arrigo, Alessandria, Italy

    A Levis

  5. Department of Infectious Disease, Ospedale San Gerardo, Monza, Italy

    A Bandera

  6. Oncoematologia AOUS Maria, Terni, Italy

    A M Liberati

  7. Department of Infectious Disease, Spedali Civili, Brescia, Italy

    S Casari

  8. Stem Cell Transplantation Unit, Spedali Civili, Brescia, Italy

    C Skert

  9. Department of Medical Oncology A, CRO, Aviano, Italy

    M Spina & U Tirelli

  10. Department of Hematology, AOU Città della Salute e della Scienza, Torino, Italy

    B Allione

  11. Department of Hematology, Ospedale San Gerardo, Monza, Italy

    L Verga

  12. Department of Transfusion Medicine, Laboratory for Stem Cell Manipulation and Cryopreservation, Spedali Civili, Brescia, Italy

    C Almici

  13. Department of Transfusion Medicine, Spedali Civili, Brescia, Italy

    P F Leali

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  1. A Re
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Correspondence to A Re.

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Re, A., Gini, G., Rupolo, M. et al. Early consolidation with high-dose therapy and autologous stem cell transplantation is a feasible and effective treatment option in HIV-associated non-Hodgkin lymphoma at high risk. Bone Marrow Transplant 53, 228–230 (2018). https://doi.org/10.1038/bmt.2017.230

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