Haploidentical Stem Cell Transplantation in Patients with Myelodysplastic Syndrome: Case Report First Experience

BACKGROUND: Allogeneic stem cell transplantation (ASCT) is a potentially curative therapeutic approach in patients with intermediate and high-risk myelodysplastic syndrome (MDS). If a family sibling or unrelated donor is not available mismatched donors are viable option for young patients with no comorbidities. The aim of this case presentation was to evaluate our first experience with haploidentical transplantation for this indication. CASE PRESENTATION: We present a case of 50 years male patient with myelodysplastic syndrome (MDS) diagnosed at University Clinic for hematology, Skopje, North Macedonia. Patient was scored in IPSS -R as high risk patient. He was referred for HLA DNA typing of family siblings and since he didn’t have identical sibling and unrelated donor, he was referred to continue treatment with haploidentical stem cell transplantation. He received Flu Bu conditioning and PTCY, cyclosporine and MMF for GVHD prophylaxis. Peripheral blood stem cells (PBSC) from his mismatched brother were infused in the amount of CD34=5.8x106/kg. He experienced prolonged engraftment, severe infective bacterial infections and CMV reactivation with clinical manifestation of CMV colitis. He was successfully treated with antiviral drug and completely resolved. His bone marrow analysis showed complete remission and chimerism evaluation revealed high donor engraftment. Patient is now +34 months post transplant in complete remission. CONCLUSION: The use of a mismatched donor increases the risk of NRM, but there is also evidence to suggest that an haploidentical donor is a valid choice, as general outcome appears to be at least similar to MUD.

CMV Infection and CMV-Specific Immune Reconstitution Following Haploidentical Stem Cell Transplantation: An Update

Haploidentical stem cell transplantation (haploSCT) has advanced to a common procedure for treating patients with hematological malignancies and immunodeficiency diseases. However, cure is seriously hampered by cytomegalovirus (CMV) infections and delayed immune reconstitution for the majority of haploidentical transplant recipients compared to HLA-matched stem cell transplantation. Three major approaches, including in vivo T-cell depletion (TCD) using antithymocyte globulin for haploSCT (in vivo TCD-haploSCT), ex vivo TCD using CD34 + positive selection for haploSCT (ex vivo TCD-haploSCT), and T-cell replete haploSCT using posttransplant cyclophosphamide (PTCy-haploSCT), are currently used worldwide. We provide an update on CMV infection and CMV-specific immune recovery in this fast-evolving field. The progress made in cellular immunotherapy of CMV infection after haploSCT is also addressed. Groundwork has been prepared for the creation of personalized avenues to enhance immune reconstitution and decrease the incidence of CMV infection after haploSCT.

Haploidentical Stem Cell Transplantation for Acute Myeloid Leukemia: Current Therapies, Challenges and Future Prospective

Haploidentical stem cell transplantation (haplo-SCT), an alternative donor source, offers a curative therapy for patients with acute myeloid leukemia (AML) who are transplant candidates. Advances in transplantation techniques, such as donor selection, conditioning regimen modification, and graft-versus-host disease prophylaxis, have successfully improved the outcomes of AML patients receiving haplo-SCT and extended the haploidentical transplant indictions for AML. Presently, treating de novo AML, secondary AML, therapy-related AML and refractory and relapsed AML with haplo-SCT can achieve comparable outcomes to those of human leukocyte antigen (HLA)-matched sibling donor transplantation (MSDT), unrelated donor transplantation or umbilical cord blood transplantation. For some subgroups of AML subjects, such as patients with positive pretransplantation minimal/measurable residual disease, recent studies suggest that haplo-SCT might be superior to MSDT in decreasing relapse and improving survival. Unfortunately, for patients with AML after haplo-SCT, relapse and infections remain the causes of death that restrict further improvement in clinical outcomes. In this review, we discuss the recent advances and challenges in haplo-SCT for AML treatment, mainly focusing on unmanipulated haplo-SCT protocols. We provide an outlook on future prospects and suggest that relapse prophylaxis, intervention, and treatment, as well as infection prevention and therapy, are areas of active research in AML patients who receive haploidentical allografts.

Recipient And Donor PTX3 rs2305619 Polymorphisms Increase The Susceptibility To Invasive Fungal Disease Following Haploidentical Stem Cell Transplantation: A Prospective Study

Background Invasive fungal disease (IFD) is a severe complication after haploidentical stem cell transplantation (haplo-HSCT) and has a poor prognosis. It has been shown that genetic polymorphism may be one possible reason for the increased risk of IFD. This study aimed to assess the role of genetic polymorphisms in the level of susceptibility to IFD in after haplo-HSCT. Methods In this study, we prospectively enrolled 251 patients who received haplo-HSCT at the Peking University Institute of Hematology from to 2016-2018. Forty-three single nucleotide polymorphisms (SNPs) of the genomic DNA were genotyped in blood samples from both recipient and donor. Results Twenty-two patients (8.8%) were diagnosed with proven or probable IFD. The independent risk factors for IFD were grades 3-4 acute graft-versus-host disease, cytomegalovirus reactivation, and recipient and donor rs2305619 (PTX3) (P<0.05) in multivariate analysis. Meanwhile, we combined the variables to develop the IFD risk scoring system and stratified patients into low- (0), intermediate- (1-2), and high-risk (3-4) groups. The 30-day and 100-day cumulative incidence of IFD in the low-, intermediate-, and high-risk groups were 0.1%, 2.4%, 10.2% and 4.5%, 4.1%, 20.3%, respectively (P=0.015). Conclusions PTX3 rs2305619 polymorphisms increase the susceptibility of IFD after haplo-HSCT in the Chinese Han population, and the IFD scoring system could be considered as a new standard for risk stratification for IFD after HSCT.