Background
Hemoglobin Bart's hydrops fetalis syndrome (BHFS) was once considered a fatal condition universally. Medical advances over the past three decades have resulted in increasing numbers of BHFS survivors. This retrospective review summarized local territory‐wide experience and outcomes of BHFS patients who received allogeneic hematopoietic stem cell transplantation (HSCT) in Hong Kong.
Methods
All BHFS patients who underwent allogeneic HSCT in Hong Kong, either in one of the two former pediatric transplant centers (Queen Mary Hospital and Prince of Wales Hospital) on or before 2019 or in the single territory‐wide pediatric transplant center (Hong Kong Children's Hospital) since 2019, from January 1, 1996, till December 31, 2020, were included. Basic demographic data, perinatal history, transplant details, long‐term outcomes, and morbidities were reviewed.
Results
Total five allogeneic HSCT were performed in two males and three females at a median age of 22 months, which include one 8/8 matched‐sibling bone marrow transplant, one 5/6 matched‐sibling cord blood transplant with HLA‐DR antigenic mismatch, two 12/12 matched‐unrelated peripheral blood stem cell transplant (PBSCT), and one haploidentical PBSCT with TCRαβ/CD45RA depletion from maternal donor. Neutrophil and platelet engrafted (>20 × 109/L) at a median of 15 and 22 days, respectively. All achieved near full donor chimerism at 1 month. All patients survived and remained transfusion‐independent without significant morbidities with median follow‐up duration of 10 years.
Conclusion
To conclude, local data demonstrated favorable outcome of allogeneic HSCT for BHFS patients, but sample number is small. Non‐directive approach in counseling and international collaboration is recommended.
Allogeneic hematopoietic stem cell transplantation is curative for transfusiondependent thalassemia, but mixed chimerism (MC) may herald graft rejection. We report a child who failed bone marrow transplant (BMT) from matched unrelated donor (MUD) successfully salvaged with haploidentical peripheral blood stem cell transplant (PBSCT), but had MC in T-lymphocyte compartment despite near-complete donor chimerism in myeloid compartment. MC was successfully improved by repeated CD45RA-depleted donor lymphocyte infusion (DLI). A 2-year-old Chinese girl with beta-thalassemia major underwent 12/12-MUD BMT with HU/AZA/Cy/Flu/ Bu/TT conditioning resulted in graft rejection. As donor refused second donation, rescue haploidentical PBSCT was performed with alemtuzumab/fludarabine/treosulfan conditioning. Harvest product was CD3/CD45RA depleted with extra products cryopreserved. Split cell chimerism performed 1-month after haplo-transplant showed 97% mother, 3% MUD, and 0% host for granulocytes but 38% mother, 62% MUD, and 0% host for CD3 + T cells. In view of low haploidentical donor chimerism in T-lymphocyte compartment, CD45RA-depleted DLI using cryopreserved product was performed on day + 38, after thymoglobulin 3 mg/kg given as T-cell depletion 3 days beforehand. T-cell chimerism improved to 51% mother and 49% MUD post-DLI. Second cryopreserved CD45RA-depleted DLI was given 17 days after the first DLI (day + 55), and 100% full chimerism of mother's T cells was gradually established without significant graft-versus-host disease (GVHD) or viral reactivation. To con-How to cite this article: Chan WYK, Kwok JSY, Chiang AKS, et al. Repeated CD45RA-depleted DLI successfully increases donor chimerism in a patient with beta-thalassemia major after haploidentical stem cell transplant. Pediatr Transplant.
To the Editor: Management of pediatric relapsed/refractory acute lymphoblastic leukemia (ALL) remains challenging despite improved outcomes over past decades. 1,2 Here, we report a successful case in achieving fourth complete remission (CR4) by haploidentical hematopoietic stem cell transplantation (HSCT) and immunotherapy. A 20-month-old male with intermediate-risk CD19-positive pre-B-ALL and central nervous system involvement (CNS3) achieved CR1 following CCCG-ALL-2015 protocol. 3 Very early marrow relapse occurred at 14 months from initial diagnosis during maintenance phase. Difficult CR2 was achieved by five courses of chemotherapy (HKPHOSG relapsed ALL 2007 and UK-ALL-R3 protocol 4,5 ) and two courses of 28-day blinatumomab infusion. He underwent 6/6 matched-unrelated cord blood transplant conditioned with fludarabine/thiotepa/busulfan/thymoglobulin, but experienced second marrow relapse 4 months post transplant. CR3 was achieved with CD19 chimeric antigen receptor T-cell (CAR-T) therapy, but third combined marrow and CNS relapse occurred at 18 months post CAR-T manifested as spinal cord compression (T5-T7, L5-S1) requiring emergency radiotherapy (1.8 Gy/Fr for four fractions to T4-T8; 2 Gy/Fr for three fractions to L5-S1). Disease persisted (57% blasts in marrow, minimal residual disease [MRD] 36.6%) despite further course of blinatumomab and chemotherapy, including clofarabine, etoposide, cyclophosphamide, bortezomib, dexamethasone, mitoxantrone, and vinorelbine. The leukemic population was CD19 + , CD20 − , CD22 + (weak), CD33 + , and cCD79a + . Child then underwent haploidentical HSCT in non-CR using paternal TCRαβ/CD45RA depleted graft.TCRαβ-depleted cells (CD34 + 5 × 10 6 /kg) were given on day 0,
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