RESUMEN

Background: Patients with leukemia relapse after allogeneic hematopoietic cell transplant (HCT) have poor survival due to toxicity and disease progression. A second HCT often offers the only curative treatment. Methods: We retrospectively reviewed our bi-institutional experience (MSKCC-USA; Utrecht-NL) with unrelated cord blood transplantation (CBT) for treatment of post-transplant relapse. Overall survival (OS) and event-free survival (EFS) were evaluated using the Kaplan-Meier method, treatment-related mortality (TRM) and relapse were evaluated using the competing risk method by Fine-Gray. Results: Twenty-six patients age < 21 years received a second (n=24) or third (n=2) HCT with CB grafts during the period 2009-2021. Median age at first HCT (HCT1) was 11.5 (range: 0.9-17.7) years and all patients received myeloablative cytoreduction. Median time from HCT1 to relapse was 12.8 (range 5.5-189) months. At CBT, median patient age was 13.5 (range 1.4-19.1) years. Diagnoses were AML: 13; ALL: 4, MDS: 5, JMML: 2; CML: 1; mixed phenotype acute leukemia: 1. Sixteen patients (62%) were in advanced stage, either CR>2 or with active disease. Median time from HCT1 to CBT was 22.2 (range 7-63.2) months. All patients engrafted after CBT. Thirteen patients developed acute GvHD; 7 had grade III or IV. With a median survivor follow-up of 46.6 (range 17.4-155) months, 3-year OS was 69.2% (95% CI 53.6-89.5%) and 3-year EFS was 64.9% (95% CI 48.8-86.4%). Eight patients died, 3 of AML relapse and 5 due to toxicity (respiratory failure [n=4], GvHD [n=1]) at a median time of 7.7 (range 5.9-14.4) months after CBT. Cumulative incidence of TRM at 3 years was 19.2% (95% CI 4.1-34.4%). Notably, all TRM events occurred in patients transplanted up to 2015; no toxicity-related deaths were seen in the 16 patients who received CBT after 2015. Cumulative incidence of relapse was 15.9% (95% CI 1.6-30.2%) at 3 years, remarkably low for these very high-risk patients. Conclusions: Survival was very encouraging following CB transplants in pediatric patients with recurrent leukemia after first HCT, and TRM has been low over the last decade. CBT needs to be strongly considered as a relatively safe salvage therapy option for post-transplant relapse.

RESUMEN

Background: Chimeric antigen receptor (CAR) T-cell therapy has demonstrated high initial complete remission (CR) rates in B-cell acute lymphoblastic leukemia (B-ALL) patients, including those who relapsed after transplant. However, the duration of remission requires improvements. Whether bridging to a second allogeneic hematopoietic stem cell transplant (allo-HSCT) after CAR-T therapy can improve long-term survival remains controversial. We retrospectively analyzed long-term follow-up data of B-ALL patients who relapsed post-transplant and received CAR-T therapy followed by consolidation second allo-HSCT to investigate whether such a treatment sequence could improve long-term survival. Methods: A single-center, retrospective study was performed between October 2017 and March 2022, involving 95 patients who received a consolidation second transplant after achieving CR from CAR-T therapy. Results: The median age of patients was 22.8 years (range: 3.3-52.8) at the second transplant. After the first transplant, 71 patients (74.7%) experienced bone marrow relapse, 16 patients (16.8%) had extramedullary relapse, 5 patients (5.3%) had both bone marrow and extramedullary relapse and 3/95 patients (3.2%) had positive minimal residual disease (MRD) only. Patients received autologous (n=57, 60.0%) or allogeneic (n=28, 29.5%) CAR-T cells, while 10 patients (10.5%) were unknown. All patients achieved CR after CAR-T therapy. Before second HSCT, 86 patients (90.5%) were MRD-negative, and 9 (9.5%) were MRD-positive. All second transplant donors were different from the first transplant donors. The median follow-up time was 623 days (range: 33-1901) after the second HSCT. The 3-year overall survival (OS) and leukemia-free survival (LFS) were 55.3% (95%CI, 44.3-66.1%) and 49.8% (95%CI, 38.7-60.9%), respectively. The 3-year relapse incidence (RI) and non-relapse mortality (NRM) were 10.5% (95%CI, 5.6-19.6%) and 43.6% (95%CI, 33.9-56.2%), respectively. In multivariate analysis, the interval from CAR-T to second HSCT ≤90 days was associated with superior LFS(HR, 4.10, 95%CI,1.64-10.24; p=0.003) and OS(HR, 2.67, 95%CI, 1.24-5.74, p=0.012), as well as reduced NRM (HR, 2.45, 95%CI, 1.14-5.24, p=0.021). Conclusions: Our study indicated that CAR-T therapy followed by consolidation second transplant could significantly improve long-term survival in B-ALL patients who relapsed post-transplant. The second transplant should be considered in suitable patients and is recommended to be performed within 90 days after CAR-T treatment.

Asunto(s)

Linfoma de Burkitt , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores Quiméricos de Antígenos , Humanos , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Enfermedad Aguda , Neoplasia Residual

RESUMEN

A minority of children experience significant graft dysfunction after undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for inborn errors of immunity (IEI). The optimal approach to salvage HSCT in this scenario is unclear with respect to conditioning regimen and stem cell source. This single-center retrospective case series reports the outcomes of salvage CD3+TCRαß/CD19-depleted mismatched family or unrelated donor stem cell transplantation (TCRαß-SCT) between 2013 and 2022 for graft dysfunction in 12 children with IEI. Outcomes of interest were overall survival (OS), event-free survival (EFS), graft-versus-host disease (GVHD)-free and event-free survival (GEFS), toxicities, GVHD, viremia and long-term graft function. In this retrospective audit of patients who underwent second CD3+TCRαß/CD19-depleted mismatched donor HSCT using treosulfan-based reduced-toxicity myeloablative conditioning, the median age at first HSCT was 8.76 months (range, 2.5 months to 6 years), and that at second TCRαß-SCT was 3.6 years (range, 1.2 to 11 years). The median interval between first and second HSCTs was 1.7 years (range, 3 months to 9 years). The primary diagnoses were severe combined immunodeficiency (SCID) (n = 5) and non-SCID IEI (n = 7). Indications for second HSCT were primary aplasia (n = 1), secondary autologous reconstitution (n = 6), refractory acute GVHD (aGVHD) (n = 3), and secondary leukemia (n = 1). Donors were either haploidentical parental donors (n = 10) or mismatched unrelated donors (n = 2). All patients received TCRαß/CD19-depleted peripheral blood stem cell (PBSC) grafts with a median CD34+ cell dose of 9.3 × 106/kg (range, 2.8 to 32.3 × 106/kg) and a median TCRαß+ cell dose of 4 × 104/kg (range, 1.3 to 19.2 × 104/kg). All patients engrafted, with a median time neutrophil and platelet recovery of 15 days (range, 12 to 24 days) and 12 days (range, 9 to 19 days). One patient developed secondary aplasia, and 1 had secondary autologous reconstitution; both underwent a successful third HSCT. Four (33%) had grade II aGVHD, and none had grade III-IV aGVHD. No patients had chronic GVHD (cGVHD), but 1 patient developed extensive cutaneous cGVHD after their third HSCT using PBSCs and antithymocyte globulin. Nine (75%) had at least 1episode of blood viremia with human herpesvirus 6 (n = 6; 50%), adenovirus (n = 6; 50%), Epstein-Barr virus (n = 3; 25%), or cytomegalovirus (n = 3; 25%). The median duration of follow-up was 2.3 years (range, .5 to 10 years), and the 2-year OS, EFS, and GEFS were 100% (95% confidence interval [CI], 0 to 100%), 73% (95% CI, 37% to 90%), and 73% (95% CI, 37% to 90%), respectively. TCRαß-SCT from mismatched family or unrelated donors, using a chemotherapy-only conditioning regimen, is a safe alternative donor salvage transplantation strategy for second HSCT in patients without a suitably matched donor.

Asunto(s)

Infecciones por Virus de Epstein-Barr , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Niño , Humanos , Lactante , Receptores de Antígenos de Linfocitos T alfa-beta , Donante no Emparentado , Estudios Retrospectivos , Viremia , Herpesvirus Humano 4 , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos

RESUMEN

Children with acute leukemia who relapse after hematopoietic cell transplantation (HCT) have few therapeutic options. We studied 251 children and young adults with acute myelogenous or lymphoblastic leukemia who underwent a second HCT for relapse after their first HCT. The median age at second HCT was 11 years, and the median interval between first and second HCT was 17 months. Most of the patients (n = 187; 75%) were in remission, received a myeloablative conditioning regimen (n = 157; 63%), and underwent unrelated donor HCT (n = 230; 92%). The 2-year probability of leukemia-free survival (LFS) was 33% after transplantation in patients in remission, compared with 19% after transplantation in patients not in remission (P = .02). The corresponding 8-year probabilities were 24% and 10% (P = .003). A higher rate of relapse contributed to the difference in LFS. The 2-year probability of relapse after transplantation was 42% in patients in remission and 56% in those in relapse (P = .05). The corresponding 8-year probabilities were 49% and 64% (P = .04). These data extend the findings of others showing that patients with a low disease burden are more likely to benefit from a second transplantation. Late relapse led to a 10% decrement in LFS beyond the second year after second HCT. This differs from first HCT, in which most relapses occur within 2 years after HCT.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Leucemia/mortalidad , Leucemia/terapia , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Masculino , Recurrencia , Tasa de Supervivencia , Factores de Tiempo , Adulto Joven

RESUMEN

Introducción: La realización de un segundo trasplante renal es la mejor opción de tratamiento de reemplazo de la función de este órgano para aquellos enfermos que han perdido un primer injerto, no obstante, parece una terapéutica poco empleada y existe la opinión de que sus resultados son inferiores a un primer trasplante. Objetivos: Determinar el porcentaje de utilización de los segundos trasplantes renales, su supervivencia e identificar los factores que influyen en estos. Métodos: Estudio analítico, retrospectivo de corte longitudinal, que abarcó todos los trasplantes renales realizados desde 1984 al 2015, excluyendo los trasplantes en receptores menores de 15 años, dobles, combinados o cuando no se pudo obtener toda la información. Se compararon los resultados de la supervivencia en general, y los de cada variable de los segundos trasplantes con los de los primarios a través de las curvas de Kaplan y Meier y de forma multivariada con una regresión de Cox. Resultados: La utilización de los segundos trasplantes renales fue de 5,6 por ciento, con una supervivencia global similar a los primarios. En el análisis comparativo de las curvas de acuerdo a las variables utilizadas no se encontraron diferencias estadísticamente significativas entre los dos grupos de estudio, de forma multivariada sí emergieron como factores de riesgo independientes para la pérdida del injerto, la edad del receptor ≥ 55 años, la edad del donante ≥ 50 años, la presencia de necrosis tubular aguda y el rechazo en los trasplantes primarios, mientras que en los secundarios esto solo ocurrió cuando la edad del donante fue ≥ a 50 años y presentaron necrosis tubular aguda. Conclusiones: El porcentaje de utilización de un segundo trasplante fue bajo, con una supervivencia similar al primero, influenciada por variables propias del receptor y del acto del trasplante(AU)

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Introduction: Performing a second kidney transplant is the best treatment option to replace the function of this organ for those patients who have lost a first graft. However, it seems a little used therapeutics and there is the opinion that its results are inferior to a first transplant. However, it seems a little used therapy and there is the opinion that its results are inferior to a first transplant. Objective: To determine the percentage of use of the second kidney transplants, their survival and identify the influential factors. Methods: An analytical, retrospective longitudinal study was done in all renal transplants performed from 1984 to 2015, excluding transplants in recipients under 15 years old, doubles, combined or when all the information could not be obtained. The results of survival in general were compared, and those of each variable of the second transplants were compared with those of the primary ones through Kaplan and Meier curves and multivariate with a Cox regression. Results: The use of a second renal transplants was 5.6 percent, with global survival similar to the primary ones. The comparative analysis of the curves according to the variables used were found no statistically significant different between the two study groups, although multivariate did emerge as independent risk factors for graft loss, the age of the recipient 55 years, the age of the donor 50 years, the presence of acute tubular necrosis and rejection in primary transplants, while in secondary cases this only occurred when the age of the donor was 50 years and they presented acute tubular necrosis. Conclusions: The percentage of a second transplant was low, with similar survival to the primary one, influenced by specific variables of the recipient and the act of transplantation(AU)

Asunto(s)

Humanos , Masculino , Femenino , Trasplante de Riñón , Supervivencia de Injerto , Estudios Retrospectivos , Estudios Longitudinales

RESUMEN

OBJECTIVE: Second allogeneic hematopoietic cell transplantation (HCT) may be indicated following relapse or graft failure following first HCT. Our retrospective single-center study sought to investigate parameters that influence post-second allogeneic HCT survival. METHOD: We investigated 92 patients who underwent second allogeneic HCT between 1980 and 2016 for relapse or graft failure following first HCT. Median age at second HCT was 41 years (range 16-68), performed for relapse in 59 patients (64%) and for graft failure in 33 patients (36%). RESULTS: On univariate analysis, 3-year OS of the entire cohort was 35% (95% CI=25-45). Eastern Cooperative Oncology Group (ECOG) score (3-year OS 48% for ECOG 0-1, 18% for ECOG 2-3, P=.0006), second HCT indication (3-year OS 43% for relapse, 20% for graft failure, P=.02), time from first HCT to relapse/graft failure (3-year OS for <12months 21%, for ≥12months 46%, P=.009), and conditioning intensity (3-year OS for MA 42% vs other regimens 23%, P=.08) significantly influenced OS. Multivariable analysis confirmed ECOG score (HR=2.15 for ECOG 2-3, 95% CI=1.32-3.51, P=.002) and second HCT indication (HR=1.67 for graft failure, 95% CI=1.02-2.75, P=.04) to independently influence survival. CONCLUSION: Second HCT may offer long-term survival particularly to patients with good performance status who relapse post-first HCT.

Asunto(s)

Anemia Aplásica/terapia , Rechazo de Injerto/diagnóstico , Supervivencia de Injerto/fisiología , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Anciano , Anemia Aplásica/inmunología , Anemia Aplásica/mortalidad , Anemia Aplásica/patología , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/mortalidad , Rechazo de Injerto/patología , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Resultado del Tratamiento

RESUMEN

Graft rejection (GR) after allogeneic stem cell transplantation (allo-SCT) occurs in 10% to 20% of patients with ß-thalassemia major (TM). There are limited data on the clinical profile and long-term outcome of patients who have had a GR. We undertook a retrospective analysis of patients who had a graft failure after allo-SCT for TM at our center. From October 1991 to June 2016, 55 of 506 patients (11%) transplanted for TM had a graft failure. An additional 7 patients with graft failure after allo-SCT done at other centers were referred to us for a second transplant. The median age was 8 years (range, 1 to 19), and there were 38 males (61.2%). Thirty-two patients (52.4%) were primary graft failures (15 with aplasia and 17 with autologous recovery) and 30 (47.6%) were secondary graft failures (5 with aplasia and 25 with autologous recovery). On conventional risk stratification 40 patients (64.5%) were class III. Seventeen patients (53.12%) with primary graft failure and 16 (53.3%) with secondary graft failure did not receive a second transplant. Twenty-nine patients (46%) with GR underwent a second allo-SCT. With the exception of 1 patient (first allo-SCT with an unrelated cord blood product), the donor for the second transplant was the same as the first transplant. Conditioning regimen for the second SCT was busulfan-based myeloablative (MAC) in 7 patients (24%), treosulfan-based MAC in 12 patients (41.3%), and the remaining received non-MAC regimens in view of pancytopenia and perceived inability to tolerate MAC. None of the patients conditioned with a treosulfan-based regimen had a GR, although 1 patient died with complications secondary to chronic graft-versus-host disease. Of the remaining 17 patients, 10 died after the second GR and 3 of regimen-related toxicity. Four are alive, of which 1 has recurrent TM and the rest are well and transfusion independent at 55, 80, and 204 months, respectively, from second transplant (all busulfan-based MAC). On a univariate analysis a nontreosulfan-based conditioning regimen and time from GR to second transplant of <1 year was significantly associated with an adverse impact. However, on a multivariate analysis only a nontreosulfan-based regimen was associated with a significant adverse impact on event-free survival (HR, 11.5; 95% CI, 1.13 to 116.4; P = .039). In conclusion, there has been a significant improvement in clinical outcomes in our experience with the use of a treosulfan-based reduced-toxicity MAC regimen for second allo-SCT for TM. It would be reasonable, where feasible, to defer the second transplant by a year after the first GR.

Asunto(s)

Busulfano/análogos & derivados , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Talasemia beta/terapia , Adolescente , Busulfano/uso terapéutico , Niño , Preescolar , Femenino , Rechazo de Injerto , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Lactante , Masculino , Reoperación , Acondicionamiento Pretrasplante/mortalidad , Resultado del Tratamiento , Adulto Joven , Talasemia beta/mortalidad

RESUMEN

Management of relapsed leukemia following allogeneic transplantation is challenging. Intensive chemotherapy, donor lymphocyte infusions (DLI), or second transplantation have some value, but most reported series describe only a limited number of patients surviving beyond 2 or 3 years following relapse. Additionally, understandable selection-bias of reports describing the outcomes of intensive management approaches for relapsed leukemia confound generalizability to a broader population. However numerous reports suggest that second allogeneic transplantation for relapsed leukemia following an initial transplant may produce extended disease control and survival for patients with favorable performance status, remission at the time of second transplant, and most importantly a long interval between initial transplant and relapse. Reduced intensity conditioning for second allografts may be preferable and little data exists to suggest that a new donor will improve disease control by inducing a stronger graft-versus-leukemia effect. Improved measures to prevent the first relapse, however, may protect more patients and produce a greater fraction enjoying extended leukemia-free survival.

Asunto(s)

Efecto Injerto vs Leucemia , Trasplante de Células Madre Hematopoyéticas , Leucemia/terapia , Transfusión de Linfocitos , Aloinjertos , Supervivencia sin Enfermedad , Humanos , Leucemia/mortalidad , Recurrencia , Tasa de Supervivencia

RESUMEN

BACKGROUND: The outcome of patients with acute lymphoblastic leukemia (ALL) relapsing after allogeneic hematopoietic cell transplantation (AlloHCT) is poor. Although morphologic remission can sometimes be achieved, such remissions are usually transient if not consolidated by a second AlloHCT (AlloHCT2). MATERIALS AND METHODS: We retrospectively analyzed the outcomes of 27 patients with ALL who had undergone AlloHCT2 for relapsed disease at our center during a 12-year period. RESULTS: With a median follow-up of 50.9 months for living patients, the 2-year overall and event-free survival were 40.7% and 29.6%, respectively. Patients with either a disease-free interval or interval between transplants of > 1 year had better overall survival (P = .02 and P = .0005) after AlloHCT2. CONCLUSION: AlloHCT2 remains a potential curative option in a subset of patients with relapsed ALL after the first AlloHCT.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Recurrencia , Retratamiento , Estudios Retrospectivos , Análisis de Supervivencia , Donantes de Tejidos , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven

RESUMEN

BACKGROUND: Stem cell transplantation is a treatment option for patients with cancer. However, a risk of adverse events might be associated with the infusion itself. An understanding of the types and grades of adverse events occurring during infusion and the patient and infusion characteristics that might be associated with these events could allow for interventions to minimize these complications. The risk factors associated with transplant-related adverse events are not well understood. MATERIALS AND METHODS: We retrospectively analyzed the adverse events occurring within 1 hour after infusion in 460 patients with cancer undergoing stem cell transplantation at the Northwestern University Robert H. Lurie Comprehensive Cancer Center from January 1, 2008 and May 1, 2011. Of the 460 patients, 382 received autologous transplants and 78 allogeneic transplants. The incidence, types, and National Cancer Institute Common Terminology Criteria grade of toxicity for adverse events were noted (primary objective). Univariate analyses were performed to study which patient and infusion characteristics might be associated with the occurrence of adverse events (secondary objectives). RESULTS: Of the 460 patients, 261 (56.7%) experienced adverse events (66.7% during allogeneic infusion and 54.7% during autologous infusion). Most events were cardiopulmonary. Univariate analysis of the infusion and patient characteristics revealed that a second transplant (P = .005) was associated with more adverse events for autologous transplant patients. For allogeneic transplant patients, a higher infusion red blood cell volume (P = .01) was associated with more adverse events. CONCLUSION: Adverse events are common during stem cell infusion and are generally cardiopulmonary.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas/efectos adversos , Células Madre Hematopoyéticas , Neoplasias/complicaciones , Adulto , Anciano , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/etiología , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Estudios Retrospectivos , Trasplante Autólogo , Trasplante Homólogo