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Outcomes of modified-eam conditioned autologous non-cryopreserved hematopoietic sct for lymphoma. A retrospective single-centre study

Bone Marrow Transplantation volume 53, pages 1596–1598 (2018)Cite this article

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High-dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT) is a standard therapy option for chemo-sensitive relapsing patients with Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (NHL) [1, 2]. The intensity of the treatment regimen is one of the variables that predict outcomes of auto-HCT [3]. However, there are limited data to guide the choice of HDT regimen prior to auto-HCT for those patients. BEAM (carmustine, etoposide, cytarabine and melphalan) is a widely used conditioning regimen for auto-HCT in patients with HL and NHL. A CIBMTR report suggested that BEAM is the best regimen for Hodgkin lymphoma, while CBV low was the best choice for follicular lymphoma [4]. Because of the non availability of Carmustine, we used a modified BEAM regimen in which we omitted carmustine and we increased the dose of cytarabine. This so-called “EAM” conditioning regimen includes the following: intravenous Etoposide 200 mg/m2 on days −5, −4, −3 and −2 (total dose of 800 mg/m2); intravenous Ara-C 1000 mg/m2 twice daily on days −5, −4, −3 and −2 (total dose of 8000 mg/m2); and intravenous Melphalan 140 mg/m2 once daily on day −1. Hematopoietic stem cells were mobilized with granulocyte colony-stimulating growth factor alone (G-CSF) Filgrastim, at a dose of 15 mcg/kg subcutaneously once daily for 5 days. Leukapheresis was performed on days −2 and −1. A volume of 8–10 L of blood was processed in each session, using the aphaeresis machine OPTIA® (Cobe, Spectra). The number of CD34+ cells is assessed immediately after the end of the cytapheresis and if a minimum number of 3 × 106 CD34+ cells/kg is not reached, another cytapheresis is performed the next morning. A median of two leukapheresis was performed (range: 1–3). A sample of the collected stem cells was obtained and total cell counts were determined using an automated cell counter; the differential cell count was done manually. For CD34+ counts, cells were labeled with fluorescein-conjugated anti-CD34+ antibodies and analyzed using a FACS scan flow cytometer to determine the absolute CD34+ count [5]. The products of the aphaeresis and 1-mL aliquots were kept in ACD-A (Baxter Healthcare, Deerfield, IL) and stored in a conventional blood bank refrigerator at +4 °C. The chemotherapy treatment regimen started once a minimum of 3 × 106 CD34+ cell/kg was obtained. The viability of cells was determined by a trypan blue dye exclusion test [6, 7]. A 1:1 matched-pair analysis, based on age and sex, was used to compare the results of patients transplanted after EAM conditioning regimen to those after BEAM (n = 29 patients). Overall survival (OS) was measured from the time of transplantation till death. Progression-free survival (PFS) was measured from the time of transplantation till death or disease progression.

We report the results of auto-HCT in 26 patients with HL and NHL receiving HDT with EAM conditioning and in 29 patients with BEAM conditioning from 2011 to 2015. The median age was 28 years (range: 17– 51) and 27 years (range: 17–52) in the EAM and the BEAM cohorts, respectively. Baseline patients characteristics are summarized in Table. 1. The median follow-up of survivors was 43.5 months, (range: 11–51). All patients had a full hematopoietic reconstitution. The two groups were comparable in term of disease status and chemosensitivity of disease at the time of transplant (Table. 1). For the EAM group, the median time to achieve an absolute neutrophil count >0.5 × 109/l was 13 days (range: 10–19). The median time to self-sustained platelet count >20 × 109/l was 16 days (range: 14–25). For the BEAM group, the median time to achieve an absolute neutrophil count >0.5 × 109/l was 14 days (range 12–32). The median time to self-sustained platelet count >20 × 109/l was 17 days (range: 15–28). Grade 4 hematological toxicity was observed in all patients for both groups. Grade 3 mucositis was observed in 12 patients and grade 3 infections were observed in 4 patients in the EAM group. In the BEAM group, grade 3 mucositis was observed in 14 patients and grade 3 infections were observed in 7 patients. Before hematopoietic recovery patients received a median of 3 units of packed red blood cells (range: 0–9) and 2 units of single donor platelet transfusion (range: 0–3) in the EAM group and a median of 3 units of packed red blood cells (range: 0–12) and 3 units of single donor platelet transfusion (range: 0–5) in the BEAM group. The transplant was well tolerated and two patient died within the first 100 days that followed transplantation in the EAM group and two patients died within the first 100 days in the BEAM group. There was no difference in transplant-related mortality for patients treated with EAM regimen compared to those with BEAM (p = 0.9).

Table 1 Baseline characteristics of patients
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  1. Department of Hematology and Cell Therapy, Etablissement Hospitalier Universitaire (EHU) 1st November, University of Oran, Oran, Algeria

    M. A. Bekadja, S. Talhi, K. Amani, S. Osmani, M. Brahimi, M. A. Mazari, A. Krim, N. Yafour, B. Entasoltan, S. Bouchama, L. Charef, F. Serradj, R. Bouhass & A. Arabi

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  1. M. A. Bekadja
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Correspondence to M. A. Bekadja.

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Bekadja, M.A., Talhi, S., Amani, K. et al. Outcomes of modified-eam conditioned autologous non-cryopreserved hematopoietic sct for lymphoma. A retrospective single-centre study. Bone Marrow Transplant 53, 1596–1598 (2018). https://doi.org/10.1038/s41409-018-0243-0

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