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A retrospective comparison of conventional intensity conditioning and reduced-intensity conditioning for allogeneic hematopoietic cell transplantation in myelofibrosis

Bone Marrow Transplantation volume 44, pages 317–320 (2009)Cite this article

Allogeneic hematopoietic cell transplantation (alloHCT) is the only curative treatment modality for patients with myelofibrosis (MF). Earlier studies using myeloablative regimens have shown that approximately 35–45% of patients achieve long-term cure from MF.1, 2, 3 The curative potential of alloHCT is related to a combination of the reduction or eradication of the malignant clone by the conditioning regimen and a graft-versus-MF effect. A major barrier to alloHCT using conventional intensity conditioning (CIC) regimens is the high TRM observed in 30–45% of patients, which restricts the use of the procedure to a limited number of young and fit patients. In the last decade, several studies have demonstrated the feasibility of non-myeloablative or reduced-intensity transplantation, collectively called reduced-intensity conditioning (RIC) regimens, in the management of MF.4, 5, 6, 7 However, comparative data on the outcomes of CIC regimens to RIC regimens in patients with MF are scanty.7 Owing to the low transplant activity for MF, it is difficult to conduct such studies. Even the large centers do only a few of these transplants every year. The majority of patients with MF are in the older age group and physicians may be hesitant to refer these patients to the transplant centers. It is not known whether patients undergoing RIC have a similar benefit from the transplant procedure as patients undergoing CIC. There is a concern that resolution of fibrosis may not be complete and there may be an increased risk of relapse in patients with MF with RIC when compared with CIC as seen in some of the hematological malignancies.

We analyzed the impact of conditioning intensity on the outcomes of alloHCT in MF. This multicenter retrospective study included 46 consecutive patients treated at three Canadian and four European transplant centers between January 1998 and December 2005. The diagnosis of MF was made on the basis of criteria published by Barosi et al.8 Data on surviving patients were updated as of October 2007. This report includes 11 patients reported in earlier studies with extended follow-up.6, 7 The indication for alloHCT was intermediate- or high-risk disease (according to the Dupriez Score) in 39 (85%) patients, whereas seven patients underwent transplant for low-risk disease because of constitutional symptoms (n=5) or recurrent thrombosis (n=2). Twenty-three patients received CIC and 23 received RIC. Of the 23 patients receiving CIC regimens, 22 received high-dose CY (120 mg/m2) in combination with fractionated TBI (1000–1200 cGY). One patient received CY 120 mg/m2 with BU (p.o. 16 mg/kg). Of the 23 patients receiving RIC, 17 patients received fludarabine (120–180 mg/m2) in combination with 8–10 mg/kg p.o. BU (n=14), 6.4 mg/kg i.v. BU (n=2) or 140 mg/m2 melphalan (n=1). Six patients received minimal conditioning with fludarabine (90 mg/m2) and low-dose TBI (200 cGY). GVHD prophylaxis in the two cohorts is summarized in Table 1. A significantly higher proportion of patient in the RIC cohort received serotherapy with anti-thymocyte globulin or alemtuzumab. Engraftment, graft failure, severity of acute and chronic GVHD were defined according to previously published standard criteria.9 PFS and overall survival were calculated from the transplant date by using the Kaplan–Meier method. The cumulative incidences were estimated for graft failure (primary and secondary), acute GVHD and chronic GVHD, whereas death from any cause was treated as a competing risk.

Table 1 Baseline patient, donor, disease and transplant-related characteristics
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Authors and Affiliations

  1. Department of Medicine, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada

    V Gupta, W Xu, J H Lipton & H Messner

  2. Department of Hematology/Oncology, University Medical Center, Hamburg, Germany

    N Kröger

  3. Department of Medicine, Karolinska University Hospital, Huddinge, Sweden

    J Aschan

  4. Department of Hematology, McMaster University, Hamilton Health Sciences Center, Hamilton, Ontario, Canada

    B Leber

  5. Department of Hematology, St George's Hospital, London, UK

    C Dalley

  6. Department of Hematology/Oncology, Ottawa Hospital, Ottawa, Ontario, Canada

    M Sabloff

  7. Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden

    M Brune

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Gupta, V., Kröger, N., Aschan, J. et al. A retrospective comparison of conventional intensity conditioning and reduced-intensity conditioning for allogeneic hematopoietic cell transplantation in myelofibrosis. Bone Marrow Transplant 44, 317–320 (2009). https://doi.org/10.1038/bmt.2009.10

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