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Outcomes following second allogeneic haematopoietic transplants using fludarabine–melphalan conditioning

Bone Marrow Transplantation volume 49, pages 852–853 (2014)Cite this article

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Second allogeneic haematopoietic cell transplant (allo-HCT2) after first allograft offers the possibility of long-term survival after relapse;1, 2, 3, 4 however, the optimal donor choice and conditioning strategy remain to be defined. All published series are retrospective and include a variety of conditioning regimens. The role of the conditioning regimen in allo-HCT2 outcomes is difficult to determine as the majority of the survival effect is thought to relate to GVL; however, recent studies have demonstrated that reduced-intensity conditioning (RIC) has improved outcomes compared with myeloablative conditioning (MAC) owing to a reduction in toxicity.5, 6 No series has reported the outcomes in patients conditioned purely with fludarabine–melphalan (Flu-Mel), which is presently the commonest RIC regimen used in Australasia.7 Here, we report a series of patients receiving allo-HCT2 using Flu-Mel conditioning. Cumulative incidence curves were constructed with appropriate events as competing risks. Survival probabilities used the Kaplan–Meier method. Multivariate analysis was performed using Cox regression.

We identified 15 adult patients reported to the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) having a second allogeneic transplant with Flu-Mel conditioning between 1998 and 2008. The median age at transplantation was 47 years (range 22–65), with six females and nine males (Table 1). The original diseases were: AML (n=10, three not in remission); Ph-positive ALL (n=1, not in remission); CML (n=3, one in accelerated phase, two in second chronic phase); and non-Hodgkin lymphoma (NHL, n=1), with a median time to relapse of 1.88 years (range=0.27–15.25 years) after initial transplant. The indication for second allograft in 13 cases was relapse of primary disease after initial transplant, with 1 case of a secondary AML 15 years after allograft for CML, occurring without the Ph chromosome, and 1 case of refractory thrombocytopenia. The majority (n=10, 67%) had MAC for their first allograft, and 8 (53%) had documented prior chronic GVHD. Only three cases received DLI before second transplant. Second transplant conditioning was fludarabine 25–30 mg/m2 for 5 days, melphalan 120–140 mg/m2 on day −1, and ATG was used in three (20%) cases. Donors were HLA-identical (n=10) or 1-locus mismatched (n=2) relatives or HLA-matched unrelated donors (n=3). The same donor was used in 9 cases (60%), with 14 (93%) using PBSC grafts. GVHD prophylaxis was CYA and MTX in the majority (n=11, 73%), the remainder used these agents alone or with mycophenolate mofetil. CMV serostatus was negative/negative in five cases (33%).

Table 1 Characteristics of patients receiving second allografts with Flu-Mel conditioning
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Authors and Affiliations

  1. Department of Haematology, St Vincent’s Hospital, Darlinghurst, New South Wales, Australia

    I Bilmon & J Moore

  2. Australasian Bone Marrow Transplant Recipient Registry, Darlinghurst, New South Wales, Australia

    I Nivison-Smith

  3. Department of Haematology, Westmead Hospital, Westmead, New South Wales, Australia

    I Bilmon & M Hertzberg

  4. Department of Haematology, Royal Melbourne Hospital, Parkville, Victoria, Australia

    D Ritchie

  5. Department of Haematology, Royal North Shore Hospital, St Leonards, New South Wales, Australia

    M Greenwood

  6. Department of Haematology, Alfred Health, Melbourne, Victoria, Australia

    A Spencer

  7. Department of Haematology, Royal Brisbane Hospital, Queensland, Herston, Australia

    G Kennedy

  8. Department of Haematology, Liverpool Hospital, Liverpool, New South Wales, Australia

    A Bryant

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  1. I Bilmon
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Correspondence to J Moore.

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Bilmon, I., Nivison-Smith, I., Hertzberg, M. et al. Outcomes following second allogeneic haematopoietic transplants using fludarabine–melphalan conditioning. Bone Marrow Transplant 49, 852–853 (2014). https://doi.org/10.1038/bmt.2014.23

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