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Allogeneic hematopoietic stem cell transplantation in patients older than 65 years with acute myeloid leukemia and myelodysplastic syndrome: a 15-year experience

Bone Marrow Transplantation volume 57, pages 678–680 (2022)Cite this article

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Allogeneic stem cell transplantation (allo-HCT) is the only curative option for intermediate and high-risk adult acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS). Despite the median age of occurrence of these diseases (>65y) [1], the majority of patients older than 65y had historically been excluded from this potentially curative option for both changes in tumor biology (conferring treatment resistance) and patient characteristics (decreasing allo-HCT tolerance) that translated into lower survival rates. Understanding which older patients are likely to benefit from allo-HCT versus low-intensity therapies or supportive care is critical. We here report our 15-year experience of allo-HCT in patients diagnosed with AML or MDS and older than 65y with remarkable results in terms of survival, transplant related mortality, relapse and graft-versus -host disase (GvHD) incidence.

Between January 2005 and December 2019, 90 consecutive adult patients aged >65y received an allo-HCT for AML or MDS at San Raffaele Hospital in Milan. Patients' and disease characteristics are described in Supplementary Data Table 1. Patients' median age was 68.29y (65.02–76.53). Donors’ median age was 38y (18–74): 64y (55–74) for sibling, 39y (20–58) for haplo, 30y (19–50) for matched unrelated donors (MUD) and 32y (18–52) for mismatched unrelated donors (MMUD). Conditioning regimens and GvHD prophylaxis are described in Supplementary Data Table 2. The conditioning regimen was treosulfan-based in 79 pts (88%): 55 pts received 14 g/mq/die, 18 pts 12 g/mq/die and 6 pts 10 g/mq/die (subgroup analysis of these patients in Supplemetary Data Table 3). In patients with high-very high disease risk index (DRI) and hematopoietic cell transplantation-specific comorbidity index (HCT-CI) <3, a second alkylating agent (thiotepa or melphalan) or TBI 4Gy was added to treosulfan. Eighty-five (94%) pts received in-vivo T-cell depletion: in 54 (63%) with antithymocyte globulin (ATG) and in 31 (37%) with post-transplant cyclophosphamide (PTCy), while 5 pts (6%) received neither ATG nor PTCy. Forty-four (49%) pts had an HCT-CI of 0, 31 (34%) pts of 1 or 2 and 15 (17%) pts ≥3. DRI was high or very high in 49 (44%) pts. Median follow-up among survivors was 35 (2.82–104) months. Median duration of hospitalization among survivors was 48 (24–198) days. All patients engrafted, except one who was rescued by a second allo-HCT. Median time from transplant to neutrophil engraftment was 21 (11–49) days. The CI of neutrophil engraftment was 78 +/− 2% at day-30 and 90 +/− 1% at day-100 from transplant and CI of day-100 platelet engraftment >20,000/mmc was 79 +/− 2%. Among the 72 pts alive at day 100, chimerism was full donor in 67 (93%). Median time from transplant to full donor chimerism was 40 days (21–853), 2 pts achieved a full donor chimerism after day 365.

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Fig. 1: Univariate analysis for Non Relapse Mortality and Overall Survival.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Simona Piemontese, Lorenzo Lazzari, Annalisa Ruggeri, Magda Marcatti, Maria Teresa Lupo Stanghellini, Fabio Giglio, Raffaella Greco, Francesca Lorentino, Daniela Clerici, Andrea Assanelli, Francesca Farina, Sara Mastaglio, Elisabetta Xue, Sarah Marktel, Luca Vago, Bernhard Gentner, Chiara Secco, Consuelo Corti, Matteo Giovanni Carrabba, Massimo Bernardi, Jacopo Peccatori & Fabio Ciceri

  2. San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Luca Vago & Bernhard Gentner

  3. Vita-Salute San Raffaele University, Milan, Italy

    Fabio Ciceri

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  1. Simona Piemontese
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  2. Lorenzo Lazzari
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Contributions

SP designed research, checked the data, analysed data and wrote the paper. LL collected the data and wrote the paper. AR analysed the data and wrote the paper. All the other authors wrote the paper.

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Correspondence to Simona Piemontese or Fabio Ciceri.

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The authors declare no competing interests.

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A written informed consent was provided by all patients, allowing the use of medical records for research in accordance with the Declaration of Helsinki.

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Piemontese, S., Lazzari, L., Ruggeri, A. et al. Allogeneic hematopoietic stem cell transplantation in patients older than 65 years with acute myeloid leukemia and myelodysplastic syndrome: a 15-year experience. Bone Marrow Transplant 57, 678–680 (2022). https://doi.org/10.1038/s41409-022-01600-1

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