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A novel reduced intensity conditioning regimen for patients with high-risk hematological malignancies undergoing allogeneic stem cell transplantation

Bone Marrow Transplantation volume 51, pages 1010–1012 (2016)Cite this article

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Non-myeloablative (NMA) and reduced intensity conditioning (RIC) allow older patients, those with comorbidities, and heavily pre-treated patients to undergo allogeneic hematopoietic cell transplantation (HCT).1, 2, 3 Consequently, the use of NMA and RIC regimens has significantly increased in the past two decades. However, as relapse remains a significant limitation, conditioning regimens that minimize non-relapse mortality (NRM) associated with myeloablative conditioning (MAC) while protecting against relapse are needed.

We have previously reported the results in double unit cord blood transplantation (CBT) recipients of a novel RIC regimen using cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2 and thiotepa 10 mg/kg with 400 cGy TBI (Cy50/Flu150/Thio10/TBI400).4, 5 Based on favorable outcomes in CBT recipients, we investigated this regimen in recipients of PBSC transplants. Twenty consecutive patients transplanted at Memorial Sloan Kettering Cancer Center between 2008 and 2013 who received Cy50/Flu150/Thio10/TBI400 were included in this retrospective analysis after obtaining approval from the center’s institutional review and privacy board. Patients with a hematological malignancy who were 18 years of age or greater with an HLA-matched or single-allele-mismatched related or unrelated donor were included. This regimen, along with GvHD prophylaxis and utilization of anti-thymocyte globulin (ATG), was selected for patients at the discretion of the treating provider if the patient was deemed to have high-risk disease for which MAC was not feasible either because of comorbidity or based on prior treatment. HLA matching was established by DNA sequence-specific oligonucleotide typing for HLA-A, -B, -C, -DRB1 and -DQB1 loci. Conditioning consisted of cyclophosphamide 50 mg/kg (day 6), fludarabine 30 mg/m2/day for 5 days (−6 to −2), thiotepa 5 mg/kg/day for 2 (days -5 and -4) and TBI 200 cGy per day for 2 (days -2 and -1) with chemotherapy doses calculated on adjusted body weight in recipients over 125% of ideal body weight. GvHD prophylaxis consisted of tacrolimus and methotrexate (n=5), sirolimus and tacrolimus with methotrexate (n=12) or without methotrexate (n=3). A recipient of a 9/10 HLA-matched unrelated donor (MUD) also received ATG. All patients received conventional PBSC grafts; nine each from HLA-matched related or MUDs and two from HLA-unrelated 1 allele mismatched donors (MMUD). Granulocyte CSF (5 μg/kg/day) was given from day 7 until neutrophil recovery. GvHD was diagnosed clinically, confirmed pathologically by biopsy whenever possible and classified according to standard criteria.6, 7 The hematopoietic stem cell transplant-comorbidity index score (HCT-CI)8 was assigned retrospectively. Data were updated as of June 2015. Overall (OS) and PFS were defined as the time from HCT until death from any cause and disease relapse or death, respectively. NRM was defined as death in a patient without disease relapse. Univariate probabilities and 95% confidence intervals of OS and PFS were estimated using Kaplan–Meier methodology, and survival distributions were compared across patient and treatment characteristics using the log-rank test. The cumulative incidence (CI) of NRM, disease relapse and GvHD was estimated based on the CI method of competing risks. Disease relapse, death in the absence of disease relapse and relapse or death in the absence of GvHD were considered competing risks for NRM, disease relapse and GvHD, respectively. All analyses were performed using R version 3.0.3 (R Foundation of Statistical Computing, Vienna, Austria).

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Acknowledgements

This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.

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Author notes

  1. G S Hobbs

    Present address: Massachusetts General Hospital, 100 Blossom Street, Boston, MA 02114, USA.,

  2. G S Hobbs and N Kaur: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    G S Hobbs, N Kaur, D Ponce, C Cho, H R Castro-Malaspina, S Giralt, J D Goldberg, A A Jakubowski, E B Papadopoulos, C Sauter, G Koehne, J N Barker & M-A Perales

  2. Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    G S Hobbs, D Ponce, C Cho, H R Castro-Malaspina, S Giralt, J D Goldberg, A A Jakubowski, E B Papadopoulos, C Sauter, G Koehne, J Yahalom, S Delvin, J N Barker & M-A Perales

  3. Harvard Medical School, Boston, MA, USA

    G S Hobbs

  4. Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    P Hilden & S Delvin

  5. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    J Yahalom

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Correspondence to M-A Perales.

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Hobbs, G., Kaur, N., Hilden, P. et al. A novel reduced intensity conditioning regimen for patients with high-risk hematological malignancies undergoing allogeneic stem cell transplantation. Bone Marrow Transplant 51, 1010–1012 (2016). https://doi.org/10.1038/bmt.2016.36

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