Allogeneic Hematopoietic Stem Cell Transplantation in Patients of 65 Years or Older: A Monocenter Analysis on 252 Patients

Advanced hematologic malignancies in older patients are unmet medical needs due to increased incidence in the aging population and the lack of effective treatment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only potential curative option for most of hematologic malignancies. However, two main limitations limited this development for a long period of time. High rates of fatal non-relapse morbidities have been progressively addressed using reduced toxicity conditioning approaches and pushing up the age limit of patients considered for transplant. The search for a donor has been also a high limitation in older population, due to the lower incidence of matched sibling donors in this population. The development of allo-HSCT from a familial haplo mismatch donor (Haplo donor) after a reduced intensity (RIC) or non-myeloablative conditioning (NMAC) has allowed for the recent development of allo-HSCT in older population.

Here we analyzed a cohort of 252 consecutive patients aged of 65 years or older treated in a single institution. Patients were selected on the following parameters: age of 65 or older on the day of transplant, first allogeneic transplant, no unrelated cord blood HSCT, hematologic malignancies, transplant between 01/01/2004 and 31/12/2018. During this period of time, the search for a one-mismatch haplotype donor (Haplo) has been introduced, the upper limit age for transplant progressively increased, more advanced diseases were considered and patients have gradually benefit from improvement in transplant care.

Patient characteristics: Median age: 67,9 (65-77) years; Male patients: 61 %; CMV Positive (70%); Acute leukemia (AL): 43%; Myelodysplastic/myeloproliferative syndromes (MDS/MPS): 35%; Chronic Leukemia: 5%; Lymphoma: 11%; Plasma cell disorders (PCD): 6%. Complete remission (CR) or Chronic phase: 155 (62%) (of whom 81 CR1 AL) Donor characteristics: median age: 62,45 (19-77); Male patients: 63 %; Matched sibling donor (MSD) (24%): 60: Unrelated donor: 75 (29%); Haplo Donor: 118 (47%). Transplant characteristics: % patients per period of time: year range: 2004-2010: 12% (Median age: 67; % Haplo D: 0; No CR/CP: 23%); 2011-2015: 40% (Median age: 68; % Haplo D: 35%; No CR/CP: 39%); 2016-2018: 48% (Median age: 69; % Haplo D: 69%; No CR/CP: 42%); PBSC: 97%; Non Myeloablative/ Reduced toxicity conditioning: 35%/65%; All patients received Post-Transplant (PostT) CSA; PT Cyclophosphamide: 49%; Pre-Transplant ATG: 47%.

Median follow-up: 17 (3-112) months; ANC recovery in 96%: 19 (10-44) days; untransfused platelet recovery above 20 in 75%: 17 (7-56) days. In evaluable patients for aGVHD: No: 58%; Grade 1: 13%; Grade 2: 14%; Grade 3: 10%; Grade 4: 4%; 85% patients were evaluable for cGVHD: No: 68%; limited: 17%; extensive:16%; 64 patients (25%) patients died from non-relapse mortality at a median of 122 days (13-3934): 2004-2010: 10/30 (33%); 2011-2015: 36/101 (25%); 2016-2018: 28/121 (23%); 53 patients relapsed/progressed at a median of 252 (30-2764) days. Three year overall and disease-free survivals are respectively of 56% (95% CI: 6.35-7.04) and 47% (95% CI: 7.17-7.55) without any difference according to age or donor type but with an impact of disease status (EFS: CR/CP 51% (95% CI: 8.7-9.5) vs others 38% ((95% CI: 11.9-12.0))

Overall these data show that allo HSCT is a valid option in older patients with high-risk malignancies. They show also that over a long period of time patient typology (more advanced diseases, older patients) and transplant practice (lower number of MSD) show a regular evolution making transplant realization more challenging. This field needs specific approach taking into account comorbidities, performance status and geriatric evaluation, to adapt treatment to every given patient. In this perspective we performed from 2015 in patients older than 65 years systematic and combined evaluation of comorbidities score, performance status and geriatric assessment (instrumental activity of daily living (AIDL); vulnerability assessment).