RESUMEN
Donor-lymphocyte infusion (DLI) for relapse following haploidentical hematopoietic cell transplantation (haploHCT) with post-transplant cyclophosphamide (PTCy) has been described in recipients of bone marrow grafts, but not recipients of G-CSF mobilized peripheral blood (PB) grafts. We retrospectively identified patients who underwent DLI following PB-haploHCT with PTCy for relapse, or loss of chimerism (LOC). Twelve patients (57%) received DLI for hematologic relapse/persistent disease, seven (33%) for extramedullary relapse and two (10%) for LOC. Sixteen (76%) received chemotherapy prior to DLI, which did not correlate with response. The most common first dose was 1 × 106 CD3+ cells/kg. Two patients developed grade I aGvHD post DLI, one had grade II and two had grade III. One developed mild skin cGvHD 1361 days post DLI. Pre-DLI aGvHD predicted post-DLI aGvHD (P=0.025). Six patients achieved CR after DLI for overt relapse, one achieved full donor chimerism after LOC. Patients with LOC or EM relapse had superior relapse-free survival following DLI (P=0.029). DLI following PB-haploHCT with PTCy is a viable salvage therapy for overt relapse or LOC without a substantial increase in GvHD, and donor lymphocytes may be collected simultaneously with graft collection to facilitate availability in patients at high risk of relapse.
Asunto(s)
Ciclofosfamida/uso terapéutico , Transfusión de Linfocitos , Trasplante de Células Madre de Sangre Periférica/métodos , Terapia Recuperativa/métodos , Anciano , Supervivencia sin Enfermedad , Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/terapia , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Donantes de Tejidos , Trasplante Haploidéntico , Resultado del TratamientoAsunto(s)
Antígenos HLA , Neoplasias Hematológicas , Isoanticuerpos/sangre , Trasplante de Células Madre de Sangre Periférica , Donante no Emparentado , Adolescente , Adulto , Anciano , Aloinjertos , Niño , Supervivencia sin Enfermedad , Femenino , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaAsunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Depleción Linfocítica , Trasplante de Células Madre de Sangre Periférica , Células Madre de Sangre Periférica , Adolescente , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Neoplasias Hematológicas/patología , Humanos , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
In recent years, the use of haploidentical donors for hematopoietic cell transplantation has expanded rapidly. Approximately 50% of patients requiring hematopoietic cell transplant lack a traditional donor. The use of HLA haploidentical-related donors is attractive due to nearly universal availability of this graft source. We summarize the current and future need for haploidentical donors and detail the rise of post-transplant cyclophosphamide as the dominant haploidentical approach. Further, we examine ongoing controversies in the field of haploidentical transplant, including conditioning regimens and graft source. Finally, we review the evidence available from preliminary comparative studies and discuss future direction of research.
Asunto(s)
Ciclofosfamida/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Donantes de Tejidos , Acondicionamiento Pretrasplante , Aloinjertos , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/tendencias , Prueba de Histocompatibilidad/métodos , Humanos , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/tendenciasRESUMEN
Post-transplant cyclophosphamide (PT-Cy) is the backbone of GvHD prophylaxis following haploidentical hematopoietic cell transplantation (haplo-HCT). PT-Cy has also been used in matched related (MRD) and unrelated (MUD) settings. It is not known whether outcomes are similar between haplo-HCT and MRD/MUD HCT when PT-Cy is used. We performed a retrospective analysis of 83 patients with AML who underwent HCT (using PT-Cy-based GvHD prophylaxis) from MRD, MUD or haploidentical donors. The groups were similar in baseline characteristics with the exception of older age in the MRD/MUD group (P=0.012). In multivariate analysis, the effect of donor type (MRD/MUD vs haploidentical) on transplant outcomes was not significant in any of the models except for faster neutrophil recovery after MRD/MUD transplants (hazard ratio: 2.21; 95% confidence interval: 1.31-3.72, P=0.002). In conclusion, we showed similar outcomes in MRD/MUD vs haploidentical HCT (except slower count recovery following haplo-HCT) when PT-Cy is used for GvHD prophylaxis. Although slower count recovery following haplo-HCT (compared with MRD/MUD transplants without PT-Cy) has been attributed to using PT-Cy, our results suggest that HLA disparity is the primary cause of this difference. Furthermore, our analysis supports PT-Cy as a viable option for GvHD prophylaxis after MRD/MUD transplants.
Asunto(s)
Ciclofosfamida/administración & dosificación , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Anciano , Donantes de Sangre , Femenino , Supervivencia de Injerto , Haplotipos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Histocompatibilidad , Humanos , Leucemia Mieloide Aguda/complicaciones , Masculino , Persona de Mediana Edad , Premedicación , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenAsunto(s)
Histocompatibilidad , Trasplante de Células Madre de Sangre Periférica/métodos , Trasplante Haploidéntico/métodos , Adulto , Anciano , Femenino , Antígenos HLA/análisis , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Linfocitos T , Trasplante Haploidéntico/mortalidad , Adulto JovenAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Adulto , Anciano , Humanos , Países BajosAsunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neoplasias Hematológicas , Movilización de Célula Madre Hematopoyética , Depleción Linfocítica , Trasplante de Células Madre de Sangre Periférica , Acondicionamiento Pretrasplante , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Factores de TiempoRESUMEN
Recent advances in allogeneic hematopoietic cell transplant (allo-HCT) have led to an increasing use of alternative donors, including banked umbilical cord blood (UCB). Despite these advances, acute GVHD (aGVHD) and chronic GVHD (cGVHD) continue to be the leading causes of early and late transplant-related mortality. ABO-mismatch has been frequently reported as a risk factor for GVHD, however, data in the UCB recipients are limited. We hypothesized that as the lymphocytes in the cord blood are thought to be naive, they will therefore be less likely to mediate GVHD. Therefore, we analyzed the impact of ABO-mismatch on aGVHD and cGVHD in recipients of single and double UCB-HCT. In both univariate and multivariate analyses, presence of ABO-mismatch did not have an impact on aGVHD or cGVHD. Whereas ABO-compatible donors are preferred in recipients of URD-HCT, ABO compatibility generally need not be considered in recipients of UCB-HCT.
