Impact of hHLA-DPB1 matching on clinical outcomes after haploidentical-related hematopoietic stem cell transplantation

ABSTRACT Background: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. Objective: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. Methods: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. Results: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. Conclusion: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

Second allogeneic peripheral blood stem cell transplants with reduced-intensity conditioning / Segundos trasplantes hematopoyéticos con esquemas de acondicionamiento de intensidad reducida

In two institutions in México, twelve patients were given a second allogeneic stem cell transplantation, using the "Mexican" non-myeloablative preparative regimen. Eight had a malignant condition (six acute leukemias, one myelofibrosis and one myelodysplasia), eleven individuals were allografted twice from the same donor and in one case, cells from two different umbilical cords were used. The median time to conduct the second allograft after the first one was 6 months (range 1-41). The five patients who failed to engraft after the first transplant failed also to engraft after the second one; all of them had been heavily transfused. Only three patients were successfully rescued with the second transplant, two with acute leukemia and one with aplastic anemia. Seven patients are alive 10-41 months (median 35) after the second transplant, but only three (25%) remain disease-free. The 52-month overall survival (SV) of the patients is 58%, whereas the median overall SV has not been reached, being above 52 months. Conducting a second allograft may be useful to rescue some individuals relapsing after a first hematopoietic allotransplant.

En dos instituciones en México se llevaron a cabo doce segundos trasplantes de células hematopoyéticas usando el "método mexicano" de acondicionamiento no mieloablativo. Ocho pacientes tenían una enfermedad maligna (seis leucemias agudas, una mielofibrosis y una mielodisplasia). Once sujetos se retrasplantaron del mismo donador y en un caso se emplearon células hematopoyéticas de dos diferentes cordones umbilicales. La mediana del tiempo transcurrido entre los dos trasplantes fue de seis meses (rango 1 a 41). Los cinco pacientes que no se injertaron con el primer trasplante tampoco se injertaron con el segundo; todos ellos habían sido multitransfundidos antes de los trasplantes. Sólo tres pacientes se pudieron rescatar con el segundo trasplante, dos con leucemia aguda y uno con anemia aplástica. Siete pacientes están vivos 10 a 41 meses (mediana 35) después del segundo trasplante, pero sólo tres (25%) se encuentran libres de enfermedad. La supervivencia (SV) global a 52 meses es de 58%, en tanto que la mediana de SV no se ha alcanzado y es mayor de 52 meses. Hacer un segundo trasplante hematopoyético puede rescatar a algunos pacientes quienes recaen después de un trasplante de médula ósea.

Trasplante de células hematopoyéticas de sangre periférica utilizando quimioterapia inmunosupresora sin destrucción de la médula ósea: "minitrasplante" / Peripheral blood hematopoietic cell transplant using immunosuppressive chemotherapy without bone marrow destruction: minitransplant

Using a nonmyeloablative, immunosuppressive, fludarabine (FLU)-base conditioning regimen, we have performed allogeneic peripheral blood stem cell transplants in 17 patients (six with chronic granulocytic leukemia, four with acute myelogenous leukemia, five with acute lymphoblastic leukemia, one with myelodysplasia and one, with thalassemia major). Conditioning regimen consisted of FLU/busulfan/cyclophosphamide or FLU melphalan. To avoid graft vs. host disease (GVHD), cyclosporine and methotrexate were used. Median granulocyte recovery time to 0.5 x 10(9) was 11 days, whereas median platelet recovery time to 20 x 10(9) was 12 days. Seven patients did not need red blood cell transfusions and four did not need platelet transfusions. In thirteen individuals (76), the procedure could be completed fully on an outpatient basis. Follow-up times range between 1 and 14 months. Five of 17 patients developed acute GVHD whereas 4/10 developed chronic GVHD. The 14-month survival (SV) is 70 and median SV is not reached. Five patients (29) have died, three due to relapse of the disease and two due to GVHD. The transplant-related mortality was 5.8. This procedure is substantially less costly than its counterpart, using in-hospital myeloablative conditioning regimens, and may represent another approach in management of patients requiring allogeneic stem cell transplant.

Bone marrow transplantation in a child with hemophagocytic lymphohistiocytosis using a less toxic conditioning regimen

Background. Hemophagocytic lymphohistiocytosis (HLH) is a rare non-neoplastic, frequently fatal disease of childhood. HLA-matched bone marrow transplantation (BMT) can bring about long-term remission and an eventual cure. Methods. We report on the beneficial effect of BMT in a 2-month-old male using a less intensive conditioning regimen. The regimen included busulfan at 4 mg/kg/day (total dose 16 mg/kg), etoposide at 300 mg/m²/day (total dose 900 mg/m²), and cyclophosphamide at 50 mg/kg/day (total dose 150 mg/kg). Prophylaxis for graft-vs.-host disease included methotrexate and cyclosporine. Results. An absolute neutrophil count of 500 µL was noticed on + day 12 (engraftment day). At present, i.e., 400 days after the procedure, the patients is asymptomatic, his physical examination is normal, and a slightly increased level of gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase are the only laboratory abnormalities. Conclusions. In this case, the conditioning regimen was adequate for the eradication of the disease and allowed persistent engraftment without significant toxicity. The results in our patient suggest that a less toxic regiment is feasible and permits rapid engraftment without compromising the effectiveness of chemotheraphy