Optimizing Haploidentical Hematopoietic Stem Cell Transplantation: Enhancing Outcomes in Hematologic Malignancies in Resource-Limited Settings

Weerapat Owattanapanich,1,* Ekapun Karoopongse,1,* Janejira Kittivorapart,2 Utairat Meeudompong,3 Natchanon Sathapanapitagkit,3 Smith Kungwankiattichai,1 Pongthep Vittayawacharin,1 Jane Jianthanakanon,1 Nawapotch Donsakul,1 Ratana Bundhit,4 Chiraporn Kongsomchit,4 Nootjaree Poonmee,4 Panpimon Luangtrakool,2 Thanatphak Warindpong,2 Sutthisak Chamsai,2 Wichitchai Bintaprasit,2 Suparat Atakulreka,1 Chutima Kunacheewa1 1Division of Hematology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 2Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Division of Sterile Pharmaceutical Production, Department of Pharmacy, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 4Department of Nursing, Siriraj Hospital, Mahidol University, Bangkok, Thailand*These authors contributed equally to this workCorrespondence: Chutima Kunacheewa, Email [email protected]: Haploidentical (haplo-) hematopoietic stem cell transplantation (HSCT) has been a standard treatment for hematological malignancies for decades. However, it remains unreimbursable in Thailand due to resource constraints. Only one-fifth of the patients suitable for HSCT in our center had matched donors. Since October 2020, haplo-HSCT has been initiated for patients without matched donors using hospital funding, as it is not reimbursed by the national health policy. This cohort study aimed to demonstrate the clinical outcomes, identify problems, manage complications, adjust the protocol of haplo-HSCT in Thailand, and advocate for making haplo-HSCT accessible for treatment in developing countries.Methods: Due to financial constraints, only eight patients with 6 acute myeloid leukemia, 1 acute lymphoblastic leukemia, and 1 lymphoma received haplo-HSCT in the first year. Unmanipulated peripheral blood stem cell haplo-HSCT was performed with post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GvHD) prophylaxis.Results: All patients experienced cytokine release syndrome (CRS) grade 1– 2 which improved after PTCy administration. One patient with active disease and HLA-DRB1 mismatch had worsening CRS after PTCy and required tocilizumab treatment. Two patients had grade 3 acute GvHD while a patient developed moderate chronic GvHD. Half of the patients had CMV viremia which was controlled with ganciclovir. At a median follow-up of 7.7 months, 7 patients were alive in remission.Conclusion: Haplo-HSCT is a feasible treatment option for hematological malignancies, yielding satisfactory outcomes with controllable side effects. Enhanced monitoring and early intervention strategies can further improve patient outcomes. Advocating for haplo-HSCT to be accessible for treatment in developing countries could significantly improve patient survival outcomes.Plain Language Summary: This study explores the use of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) to treat blood cancers in Thailand, where financial constraints often limit access to advanced medical treatments. Stem cell transplantation is a vital therapy, but finding fully matched donors remains a challenge. Our hospital started providing haplo-HSCT in October 2020 for patients without suitable donors. Over the first year, eight patients with blood cancers, including acute leukemia and lymphoma, received this treatment. A specialized method was applied to reduce complications and improve success rates. One key complication observed was cytokine release syndrome (CRS), an inflammatory response that can occur after stem cell transplants. All patients developed CRS, presenting symptoms like fever and diarrhea within one day after the transplant. Most cases were mild to moderate and resolved after routine treatments, including post-transplant cyclophosphamide (PTCy). However, two patients required additional treatment with a drug called tocilizumab due to worsening symptoms. In one severe case, a patient experienced persistent high fever and severe diarrhea, along with elevated markers of inflammation. Despite initial treatments, this patient needed multiple doses of tocilizumab before their condition stabilized. Overall, the results demonstrated positive outcomes. At a median follow-up of about eight months, seven patients were alive and cancer-free. This study highlights that haplo-HSCT is a viable treatment option even in resource-limited settings, with proper monitoring and timely medical interventions for managing complications like CRS. Making this treatment accessible in developing countries could significantly improve survival rates for patients with blood cancers.Keywords: haplo-transplantation, cytokine release syndrome, resource-limited countries, haploidentical transplantation, post-transplant cyclophosphamide, hematologic malignancies, resource-limited settings