Allogeneic Hematopoietic Stem Cell Transplant in Children with Relapsed/Refractory Acute Lymphoblastic Leukemia: Ambulatory or in-Hospital?

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option in patients with oncohematological or non-malignant hematological diseases. Significant advances have recently proposed the use of alternative sources of donors, and outpatient reduced-intensity conditioning regimens, which have expanded the possibility of patient transplants, and improved overall (OS) and disease-free survival (DFS). Allo-HSCT has been successfully conducted in the pediatric population, mainly in relapsed or refractory acute lymphoblastic leukemia (R/R ALL).

Objective: To compare the long-term outcomes of allogeneic transplantation in children with R/R ALL using low-intensity conditioning regimens in inpatients vs. outpatients.

Method: Children with R/R ALL were grafted using reduced-intensity conditioning regimens based on the “Mexican conditioning method.” The initially administered protocol, on an outpatient basis, included: Fludarabine (total dose 150 mg/m²), pre-transplant cyclophosphamide (total dose of 2000 mg/m²), and daily post-transplant cyclophosphamide on days +3 and +4, either as a conventional dose (50 mg/kg IV) or a reduced dose (25-30 mg/kg IV). Patients allografted in-hospital received: Fludarabine (75 mg/m²), total dose cyclophosphamide (1500 mg/m²), busulfan (0.8 mg/kg/dose, 4 doses per day) or melphalan (140 mg/m2). The protocol has been registered in www.clinicalTrials.gov, identification NCT05780554.

The primary end-point of the study was OS, and the secondary end-point was the prevalence of acute and chronic graft-versus-host disease (GVHD).

Results: 34 consecutive patients were analyzed, 19 were grafted in-hospital, and 15 on an outpatient basis. In the statistical analysis, no significant difference was found in terms of age (outpatients 8.3 +/- 5.0 yrs. vs. in-patient 7.6 +/- 4.3 yrs.; p=0.662), sex (outpatients 10 female and 5 male vs. in-patient 12 and 7, respectively) and acute GVHD (outpatient 6 vs. in-patient 7; p=0.432).

The median follow-up in the outpatient subset was 28.2 months (IQR: 2.93 - 81.67) and 20.7 months (IQR: 11.2 - 28.63) (p=0.837) in the hospitalized group. Recovery time, >500 neutrophils, was the same in the two groups,14-days outpatient (IQR=10-18) vs. 14-days inpatient (IQR= 14 - 18.25), p=0.768), while platelet recovery time was significantly shorter in outpatients (12-days outpatient (IQR=5 - 13) vs. 15-days inpatients (IQR= 13.25 - 17), p= 0.004), as was the prevalence of chronic GVHD (10% outpatient vs. 61% inpatient, p=0.008). In the inpatient group, 14/19 (74%) transplants were from haploidentical donors versus 4/15 (27%) in the outpatient group; this difference was significant (p=0.0063). The likelihood of completing the HSCT as an outpatient was greater if grafts were obtained from matched siblings rather than haploidentical donors. The OS of children allografted in-hospital was 57.89% at 20.7 months, whereas in outpatients. it was 40% at 28.2 months (p=0.683), a non-significant difference.

Conclusions: These results suggest that treatment of refractory or relapsed ALL in children with an allogeneic HSCT following the low-intensity conditioning scheme and on an outpatient basis, is a safe alternative and not significantly different when compared with children treated in-hospital. The possibility of conducting outpatient HSCT was greater if grafts were obtained from identical siblings than from haploidentical donors. Further, the prevalence of chronic GVHD was lower in children allografted on an outpatient basis.

Gomez-Almaguer:AbbVie: Research Funding, Speakers Bureau; Amgen: Consultancy, Other: Advisory board, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Advisory board, Speakers Bureau; Seattle Genetics: Research Funding; Incyte: Research Funding; Blueprint Medicines: Research Funding; Roche: Speakers Bureau; Sanofi: Speakers Bureau; Astex Pharmaceuticals: Research Funding; Tevas: Speakers Bureau; BMS: Consultancy, Other: Advisory board, Speakers Bureau; Takeda: Consultancy, Other: Advisory board, Research Funding, Speakers Bureau; Novartis: Consultancy, Other: Advisory board, Speakers Bureau; Kartos Therapeutics: Research Funding; Gilead/Forty Seven: Research Funding; ConstellationPharmaceuticals: Research Funding.