RESUMO
LRBA deficiency is an inborn error of immunity defined by autoimmunity, lymphoproliferation, recurrent infections, cytopenia, and inflammatory bowel disease. Despite recent advances in managing this disease with targeted biologic therapy, haematopoietic stem cell transplant (HSCT) remains the only cure. However, great variability exists between protocols used to transplant patients with LRBA deficiency. We describe a cohort of seven patients with LRBA deficiency who underwent HSCT using a myeloablative, reduced toxicity regime of fludarabine, treosulfan, and thiotepa at two transplantation centres from 2016 to 2019. Data were collected both retrospectively and prospectively, measuring time to engraftment, infectious complications, incidence of graft versus host disease, and post-transplantation chimerism. Six of seven patients survived transplantation, and four of six surviving patients achieving treatment-free survival. We thus recommend that HSCT with fludarabine, treosulfan, and thiotepa-based conditioning be considered in patients with LRBA deficiency.
Assuntos
Bussulfano , Transplante de Células-Tronco Hematopoéticas , Tiotepa , Condicionamento Pré-Transplante , Vidarabina , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Bussulfano/análogos & derivados , Bussulfano/uso terapêutico , Condicionamento Pré-Transplante/métodos , Tiotepa/uso terapêutico , Masculino , Feminino , Lactente , Pré-Escolar , Doença Enxerto-Hospedeiro/etiologia , Criança , Estudos Retrospectivos , Resultado do Tratamento , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/terapiaRESUMO
The benefit of high-dose melphalan followed by autologous hematopoietic stem cell transplantation (HDM-ASCT) for multiple myeloma (MM) patients with renal insufficiency (RI) is debated. A systematic review and meta-analysis were conducted to assess the safety and efficacy of HDM-ASCT in MM patients with RIs, and the findings were compared with real-world data. The study included 26 articles, 13 of which were pooled for meta-analysis. We compared three different types of MM patients with RI against MM patients with normal renal function (NRF). These patients were: MM patients with RI at the time of transplantation; MM patients with RI at the time of diagnosis; MM patients with RI at diagnosis but with NRF at transplantation. The meta-analysis indicated that MM patients with RIs conditioned with melphalan ≤ 140 mg/m2 followed by ASCT had transplant-related mortality rates comparable to those without RIs. The complete response rates post-ASCT were similar between MM patients with RIs and those with NRF. Although progression-free survival (PFS) was statistically similar between the groups, MM patients with RIs had significantly poorer overall survival (OS) than those with NRF. The real-world data supported these findings. With a reduced dose of melphalan, ASCT is safe and effective for MM patients with RI. MM patients with RI have similar complete response rates and PFS after ASCT compared to MM patients with NRF. The lower OS in MM patients with RI indicates the need for further research to improve OS in these patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Melfalan , Mieloma Múltiplo , Insuficiência Renal , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Insuficiência Renal/etiologia , Insuficiência Renal/mortalidade , Insuficiência Renal/terapia , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE AND BACKGROUND: Sinusoidal obstruction syndrome (SOS) is a life-threatening complication in hematopoietic stem cell transplantation (HSCT) patients. However, the related risk factors in pediatric and young adult HSCT recipients remain unclear. Thus, we conducted this meta-analysis to identify potential risk factors for SOS in children and young adults undergoing HSCT. METHOD: We acquired related articles through searching PubMed, EMBASE, and the Cochrane Library up to May 31, 2024. We calculated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to identify potential risk factors. RESULTS: A total of 12 studies with 7644 HSCT recipients were included. Bone marrow transplantation (OR = 1.35, 95% CI: 1.03-1.77, I2 = 0%), busulfan (BU) (OR = 3.63, 95% CI: 1.78-7.38, I2 = 70%), and fludarabine (FLU) (OR = 1.55, 95% CI: 1.09-2.21, I2 = 16%) were risk factors for SOS after HSCT in children and young adults. CONCLUSION: Bone marrow transplantation and the use of BU or FLU might be risk factors for SOS after HSCT in children and young adults.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Adolescente , Criança , Humanos , Adulto Jovem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/epidemiologia , Hepatopatia Veno-Oclusiva/etiologia , Prognóstico , Fatores de Risco , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodosRESUMO
The aim of this retrospective study was to evaluate the efficiency and safety of total body irradiation plus cyclophosphamide (TBI/Cy) followed by autogenetic hematopoietic stem cell transplantation (auto-HSCT) in T-LBL/ALL patients that cannot receive allogeneic hematopoietic stem cell transplant (allo-HSCT). Between 2013 and 2023, 24 patients received auto-HSCT following by TBI/Cy, 26 patients underwent allo-HSCT, all patients achieved completed hematopoietic reconstitution after HSCT. The progression free survival (PFS) and overall survival (OS) had no statistically significant differences between the two groups (P = 0.791, HR 1.127, 95%CI 0.456-2.785; P = 0.456, HR 0.685, 95%CI 0.256-1.828). Although the cumulative incidence of relapse was lower for patients who received allo-HSCT than auto-HSCT (P = 0.033, HR 3.707, 95%CI 1.188-11.570, 2-year relapse 11.5% vs. 33.3%), the incidence of non-relapse mortality (NRM) was higher than that in the auto-HSCT group (P = 0.014, HR 0.000, 95%CI -1.000 - -1.000, 2-year NRM, 23.1% vs. 0%). Trough Landmark analysis, the two groups showed a statistically significant difference in 3-year PFS and 4-year OS curves (Figure S2A&B, P = 0.039, HR 0.426, 95%CI 0.163-1.117; P = 0.014, HR 0.317, 95%CI 0.113-0.887). By COX analysis, poor baseline performance status (ECOG-PS ≥ 2) and CNS involvement were risk factors for PFS and OS. In conclusion, TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL.
Assuntos
Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas , Irradiação Corporal Total , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Masculino , Feminino , Adulto , Adolescente , Estudos Retrospectivos , Adulto Jovem , Ciclofosfamida/uso terapêutico , Transplante Homólogo , Criança , Condicionamento Pré-Transplante/métodos , Pessoa de Meia-Idade , Transplante Autólogo , Pré-Escolar , Doença Enxerto-Hospedeiro/etiologiaRESUMO
The annual number of human leukocyte antigen (HLA)-haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HCT) is increasing steadily. Comparative studies about haplo-HCT versus HCT with HLA-matched sibling donors (MSD-HCT) have been tried in acute myeloid leukemia and B-cell acute lymphoblastic leukemia/lymphoma (ALL). Few studies were reported in adult T-cell ALL (T-ALL). In this retrospective study, a total of 88 consecutive patients with T-ALL were enrolled who underwent MSD-HCT (n = 24) and haplo-HCT (n = 64) with antithymocyte globulin (ATG)-based graft versus host disease (GVHD) prophylaxis between 2010 and 2022. Median follow-up for survivors was similar (43.5 [range: 7-88] months for MSD-HCT versus 43.5 (range: 6-144) months in the Haplo-HCT group). The 100-day cumulative incidence of grade II to IV acute GVHD (aGVHD) was similar, 33% (95% confidence interval [CI], 16%-52%) after MSD-HCT versus 44% (95% CI, 31%-55%) after haplo-HCT, P = 0.52. The cumulative incidences of grade III-IV aGVHD were 8% (95% CI, 1%-23%) in the MSD-HCT group and 5% (95% CI, 1%-12%) in the haplo-HCT group (P = 0.50). The 2-year cumulative incidence of chronic GVHD (limited and extensive) in the haplo-HCT, 11% (95% CI, 5%-20%) was significantly lower than that in the MSD-HCT group (42% [95% CI, 21%-62%], P = 0.002). The cumulative incidence of 4-year relapse rates (44% versus 37%, P = 0.56) and non-relapse mortality (7% versus 21%, P = 0.08) did not differ between these two groups. There were also no differences in 4-year overall survival (46% versus 47%, P = 0.44) and progression-free survival (49% versus 42%, P = 0.45) between these two groups. On multivariate analysis, using busulfan/fludarabine (BU/Flu) conditioning regimen was found to be associated with worse clinical outcome. Our results suggested that ATG-based haplo-HCT platform could work as an alternative to MSD-HCT for adult patients with T-ALL. Compared with MSD-HCT, haplo-HCT might carry a low risk for cGVHD.
Assuntos
Soro Antilinfocitário , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Irmãos , Humanos , Adulto , Feminino , Masculino , Soro Antilinfocitário/uso terapêutico , Pessoa de Meia-Idade , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto Jovem , Estudos Retrospectivos , Transplante Haploidêntico/métodos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Doença CrônicaRESUMO
Graft rejection and Graft-versus-host disease (GVHD) are some of the significant factors resulting in morbidity and mortality following allogeneic hematopoietic cell transplantation. Prophylaxis for GVHD using T-cell depleting agents is helpful in reducing the transplant-related mortality and graft rejection. Both tATG and fATG exhibit varied amounts of antibody specificities and perform distinct immunomodulatory effects, regardless of their capacity to deplete T-lymphocytes. We conducted this single-center, retrospective study at our center to compare both formulations. Twenty-six patients were included in the study, 13 in each cohort. The median age at diagnosis of ß-thalassemia was 5 months (range, 3-12 months) in the tATG group and 6 months (range, 3-9 months) in the f-ATG group, respectively. Acute GVHD was observed in 1 (7.7) and 2(15.4) in the tATG and fATG group, respectively. No cases of chronic GVHD were observed in either group. There was no difference in the mixed chimerism observed at 6 months in both groups, tATG (n = 5, 38.5%) and fATG (n = 6, 46.15). There was 1 (7.6) rejection at day +72 observed in the tATG group, whereas no rejection was observed in the fATG group. At a mean follow-up duration of 288 days since transplant, there were no deaths in either of the groups. In conclusion, both ATG preparations showed equivalent effectiveness in preventing rejections and GVHD. However, further larger studies are required to establish the long-term efficacy and safety of both formulations in ASCT.
Assuntos
Soro Antilinfocitário , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Humanos , Condicionamento Pré-Transplante/métodos , Soro Antilinfocitário/administração & dosagem , Masculino , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/etiologia , Estudos Retrospectivos , Transplante Homólogo , Lactente , Irmãos , Centros de Atenção Terciária , Doadores de Tecidos , Talassemia/terapia , Talassemia beta/terapiaRESUMO
BACKGROUND: IL10RA (IL10 receptor subunit alpha) deficiency is an autosomal recessive disease that causes inflammatory bowel disease during early infancy. Its clinical course is often fatal and the only curative treatment is allogeneic hematopoietic cell transplantation (HCT). In Japan, only case reports are available, and there are no comprehensive reports of treatment outcomes. METHODS: We retrospectively analyzed patients with IL10RA deficiency in Japan. RESULTS: Two newly identified and five previously reported patients were included in this study. Five patients underwent HCT; one untransplanted patient survived to age 14, and one died of influenza encephalopathy before transplantation. All five HCT recipients underwent HCT at the age before 2 years. They all were conditioned with fludarabine/busulfan- or fludarabine /melphalan-based regimens. The donor source was human leukocyte antigen haploidentical donor bone marrow (BM) for two patients and unrelated umbilical cord blood (CB) for two patients. One patient experienced graft failure with unrelated CB and required a second transplant with unrelated BM. All patients who underwent HCT survived and demonstrated an improved performance status. CONCLUSION: In cases of IL10RA deficiency, the need for transplantation should be promptly assessed, and early transplantation should be considered. (190/250).
Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Japão , Masculino , Feminino , Lactente , Resultado do Tratamento , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Adolescente , Pré-Escolar , Subunidade alfa de Receptor de Interleucina-10/genética , Subunidade alfa de Receptor de Interleucina-10/deficiência , Criança , Doenças Inflamatórias Intestinais/terapiaRESUMO
BACKGROUND: Total body irradiation (TBI)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for selected patients with acute myeloid leukemia (AML). Yet, secondary malignancies contribute to long-term morbidity and mortality with TBI potentially influencing these risks. METHODS: This retrospective study analyzed the cumulative incidences of secondary solid malignancies and precancerous lesions of 89 consecutive AML patients after TBI-based conditioning before 1st allo-HSCT between 2000 and 2016. TBI was performed with an average dose rate of 4 cGy/min and a twice-daily fractionation. Cause-specific hazard models analyzed risk factors for secondary malignancies/precancerous lesions and the competing risks of dying before developing secondary malignancies/precancerous lesions. RESULTS: The median patient age at TBI was 42.5 years (interquartile range, 32.5-51.2), while the median follow-up was 15.2 years (interquartile range, 13.0-18.2). Most patients received a myeloablative conditioning (MAC) containing 8 Gy (n = 47) and 12 Gy TBI (n = 11). Reduced-intensity regimens (RIC, 4 Gy TBI) were applied in 31 patients. Of note, patients receiving RIC were older than patients receiving MAC. The most common cancer types were non-squamous cell carcinomas (n = 14) after exclusion of a patient diagnosed with sarcoma within less than a year after TBI. The cumulative incidences of secondary malignancies and precancerous lesions were 8% (95%CI, 4-16), 14% (95%CI, 7-23), and 17% (95%CI, 9-27) at 10, 15 and 20 years, while the cumulative incidences of premature deaths were 59% (95%CI, 48-69), 59% (95%CI, 48-69), and 64% (95%CI, 49-76). In multivariate analyses, higher patient age at TBI was associated with lower rates of secondary malignancies/precancerous lesions, while higher patient age translated into a trend towards premature deaths (before patients could develop malignancies). Higher TBI doses, mainly applied in younger patients, translated into lower rates of secondary malignancies/precancerous lesions while lacking associations with mortality. Chronic GVHD requiring systemic immunosuppression was associated with premature deaths. CONCLUSIONS: Although this study indicates an inverse relationship between TBI doses applied and treatment-related malignancies, confounding by competing risks is present. The age dependency may be explained by the fact that older patients had a lower life expectancy independent of malignancies, illustrating the pitfalls of competing risks. TRIAL REGISTRATION: The study was retrospectively registered.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Segunda Neoplasia Primária , Irradiação Corporal Total , Humanos , Pessoa de Meia-Idade , Masculino , Irradiação Corporal Total/efeitos adversos , Feminino , Adulto , Estudos Retrospectivos , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/mortalidade , Sobreviventes de Câncer/estatística & dados numéricos , Fatores de Risco , Transplante Homólogo , SeguimentosRESUMO
BACKGROUND: Various reduced-intensity conditioning/reduced-toxicity conditioning regimens have been developed for patients receiving allogeneic hematopoietic cell transplantation. The balance between disease relapse and toxicity can be partly dependent on reduced-intensity conditioning/reduced-toxicity conditioning regimens. This retrospective study aimed to compare the nonrelapse mortality, relapse incidence, progression-free survival, and overall survival rates between the fludarabine/melphalan/reduced-dose busulfan (Flu/Mel/Bu2; busulfan at a dose of 6.4 mg/kg intravenously) and fludarabine/melphalan/full-dose busulfan (Flu/Mel/Bu4; busulfan at a dose of 12.8 mg/kg intravenously) regimens in patients receiving umbilical cord blood transplantation. METHOD: Eighty-seven adult patients who received the Flu/Mel/Bu2 (n = 45) or Flu/Mel/Bu4 (n = 42) regimen as a conditioning regimen before umbilical cord blood transplantation at our institution between January 2013 and December 2022 were included in this study. RESULTS: There were no significant differences in terms of clinical outcomes including nonrelapse mortality, relapse incidence, progression-free survival, and overall survival rates between the two regimens. Further, even in higher-risk patients classified according to the Refined Disease Risk Index, the Flu/Mel/Bu2 regimen was comparable to the Flu/Mel/Bu4 regimen. CONCLUSION: The novel Flu/Mel/Bu2 regimen could be applied in clinical settings as it can be tolerated and effective in older patients.
Assuntos
Bussulfano , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Melfalan , Condicionamento Pré-Transplante , Vidarabina , Humanos , Bussulfano/administração & dosagem , Vidarabina/análogos & derivados , Vidarabina/administração & dosagem , Melfalan/administração & dosagem , Estudos Retrospectivos , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Adulto Jovem , Idoso , AdolescenteRESUMO
Introduction: Humanized mouse models to recapitulate human biological systems still have limitations, such as the onset of lethal graft-versus-host disease (GvHD), a variable success rate, and the low accessibility of total body irradiation (TBI). Recently, mice modified with the CD47-SIRPA axis have been studied to improve humanized mouse models. However, such trials have been rarely applied in NOD mice. In this study, we created a novel mouse strain, NOD-CD47nullRag2nullIL-2rγnull (RTKO) mice, and applied it to generate humanized mice. Methods: Four-week-old female NOD-Rag2nullIL-2rγnull (RID) and RTKO mice pre-conditioned with TBI or busulfan (BSF) injection were used for generating human CD34+ hematopoietic stem cell (HSC) engrafted humanized mice. Clinical signs were observed twice a week, and body weight was measured once a week. Flow cytometry for human leukocyte antigens was performed at intervals of four weeks or two weeks, and mice were sacrificed at 48 weeks after HSC injection. Results: For a long period from 16 to 40 weeks post transplantation, the percentage of hCD45 was mostly maintained above 25% in all groups, and it was sustained the longest and highest in the RTKO BSF group. Reconstruction of human leukocytes, including hCD3, was also most prominent in the RTKO BSF group. Only two mice died before 40 weeks post transplantation in all groups, and there were no life-threatening GvHD lesions except in the dead mice. The occurrence of GvHD has been identified as mainly due to human T cells infiltrating tissues and their related cytokines. Discussion: Humanized mouse models under all conditions applied in this study are considered suitable models for long-term experiments based on the improvement of human leukocytes reconstruction and the stable animal health. Especially, RTKO mice pretreated with BSF are expected to be a valuable platform not only for generating humanized mice but also for various immune research fields.
Assuntos
Bussulfano , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Camundongos Endogâmicos NOD , Camundongos Knockout , Condicionamento Pré-Transplante , Animais , Bussulfano/farmacologia , Humanos , Camundongos , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Células-Tronco Hematopoéticas/metabolismo , Feminino , Subunidade gama Comum de Receptores de Interleucina/genética , Subunidade gama Comum de Receptores de Interleucina/deficiência , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/imunologia , Modelos Animais de Doenças , Irradiação Corporal TotalRESUMO
INTRODUCTION: Allogeneic Hematopoietic cell transplantation (allo-HCT) remains the only curative therapy for myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The impact of spliceosome mutations on allo-HCT outcome is unclear and further understanding is needed to assess the implications of this class of mutations on risk of relapse, overall survival (OS) and non-relapse mortality (NRM) in order to make decision regarding timing of allo-HCT. We examined the allo-HCT outcomes of MDS/CMML patients based on their spliceosome mutation profile to understand the impact of these mutations on transplant outcomes. OBJECTIVE: To compare outcomes of MDS/CMML patients with and without spliceosome mutations undergoing allo-HCT. METHODS: This is a single institution, retrospective study of MDS/CMML patients who underwent allo-HCT with myeloablative or reduced intensity conditioning (RIC) regimen at City of Hope from January 2016 to December 2021. Among them, patients who underwent molecular mutation profiling by NGS (Next Generation Sequencing) for a set of genes known to be mutated in myeloid neoplasms are included in this analysis. We compared OS, relapse free survival, NRM and acute/chronic graft versus host disease (GVHD) incidence between the spliceosome-mutated and unmutated groups. RESULTS: We identified 258 consecutive MDS/CMML patients who underwent allo-HCT. Of these, 126 (48.8â¯%) patients had molecular profiling done among whom 57 (45.2â¯%) patients carried a spliceosome mutation. 84.9â¯% of patients had MDS and 55.6â¯% underwent a matched unrelated donor transplant. The median age for the whole cohort was 66 years (range 12-77).78.6â¯% and 73.7â¯% received RIC in the spliceosome and non-spliceosome groups, respectively. The 2-year OS for the whole cohort was 66.5â¯% (95â¯%CI 0.55-0.75) with a day 100 NRM of 7.1â¯% and 2-year cumulative incidence of relapse of 20â¯%. Grade II-IV acute GVHD at day 100 was 36.3â¯% (95â¯% CI 0.27-0.44) and any chronic GVHD at 2-years was 48.4â¯% (95â¯% CI 0.37-0.58). Patients who carried a spliceosome mutation had a significantly better 2-year survival of 83.8â¯% vs 55.9â¯% in the non-spliceosome group (P=0.002) and a better PFS of 73.7â¯% vs 50.0â¯% (P=0.007). There was no difference in the cumulative incidence of relapse at 2-years 15.9â¯% vs 18.5â¯% (P=0.59) between two groups but the spliceosome group had a significantly lower NRM at 2-years 10.4â¯% vs 31.5â¯% (P=0.009). There was no difference in incidence of acute or chronic GVHD between the two groups. CONCLUSIONS: Among patients with MDS or CMML who underwent allo-HCT, our study shows better OS for patients who have spliceosome mutations due to lower NRM compared to those carrying non- spliceosome mutations. This favorable outcome of the spliceosome-mutated patients could have implications for timing of allo-HCT, particularly for patients in the intermediate MDS prognostic risk groups.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Crônica , Mutação , Síndromes Mielodisplásicas , Spliceossomos , Transplante Homólogo , Humanos , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Síndromes Mielodisplásicas/mortalidade , Spliceossomos/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/terapia , Leucemia Mielomonocítica Crônica/mortalidade , Estudos Retrospectivos , Adulto , Idoso , Condicionamento Pré-Transplante/métodos , Taxa de Sobrevida , Prognóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Adulto JovemRESUMO
BACKGROUND: Conventional conditioning regimens for children with lymphoid malignancy undergoing allogeneic hematopoietic cell transplantation (HCT) are myeloablative and involve high-dose total body irradiation (TBI). Such regimens are associated with significant late complications. OBSERVATIONS: Here, we used a reduced-toxicity conditioning regimen comprising fludarabine, cytarabine, melphalan, and low-dose TBI (FLAMEL) to treat 5 patients with lymphoid malignancy before HCT. Four patients maintained complete remission (range, 18 to 63 mo), whereas the remaining patient who had positive minimal residual disease (MRD) before HCT relapsed. CONCLUSIONS: FLAMEL might be a suitable conditioning regimen for children with lymphoid malignancy if pre-HCT MRD is negative.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Melfalan , Condicionamento Pré-Transplante , Vidarabina , Humanos , Condicionamento Pré-Transplante/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Masculino , Criança , Feminino , Vidarabina/análogos & derivados , Vidarabina/administração & dosagem , Vidarabina/uso terapêutico , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Adolescente , Irradiação Corporal Total , Transplante Homólogo/métodos , Pré-Escolar , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasia ResidualAssuntos
Anemia Falciforme , Transplante de Células-Tronco Hematopoéticas , Transplante Haploidêntico , Humanos , Anemia Falciforme/terapia , Criança , Masculino , Feminino , Adolescente , Transplante de Células-Tronco Hematopoéticas/métodos , Pré-Escolar , Transplante Haploidêntico/métodos , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/etiologia , Condicionamento Pré-Transplante/métodosRESUMO
BACKGROUND: Autologous stem cell transplantation (ASCT) is a pivotal treatment for lymphoma patients. The BeEAM regimen (Bendamustine, Etoposide, Cytarabine, Melphalan) traditionally relies on cryopreservation, whereas the CEM regimen (Carboplatin, Etoposide, Melphalan) has been optimized for short-duration administration without the need for cryopreservation. This study rigorously compares the clinical and safety profiles of the BeEAM and CEM regimens. METHODS: A controlled, randomized clinical trial was conducted with 58 lymphoma patients undergoing ASCT at the International Medical Center (IMC) in Cairo, Egypt. Patients were randomly assigned to either the BeEAM (n = 29) or CEM (n = 29) regimen, with an 18-month follow-up period. Clinical and safety outcomes were meticulously compared, focusing on time to engraftment for neutrophils and platelets, side effects, length of hospitalization, transplant-related mortality (TRM), and survival rates. RESULTS: The findings demonstrate a significant advantage for the CEM regimen. Neutrophil recovery was markedly faster in the CEM group, averaging 8.5 days compared to 14.5 days in the BeEAM group (p < 0.0001). Platelet recovery was similarly expedited, with 11 days in the CEM group versus 23 days in the BeEAM group (p < 0.0001). Hospitalization duration was substantially shorter for CEM patients, averaging 18.5 days compared to 30 days for those on BeEAM (p < 0.0001). Furthermore, overall survival (OS) was significantly higher in the CEM group at 96.55% (95% CI: 84.91-99.44%) compared to 79.31% (95% CI: 63.11-89.75%) in the BeEAM group (p = 0.049). Progression-free survival (PFS) was also notably superior in the CEM group, at 86.21% (95% CI: 86.14-86.28%) versus 62.07% (95% CI: 61.94-62.20%) in the BeEAM group (p = 0.036). CONCLUSION: The CEM regimen might demonstrate superiority over the BeEAM regimen, with faster neutrophil and platelet recovery, reduced hospitalization time, and significantly improved overall and progression-free survival rates. Future studies with longer duration and larger sample sizes are warranted. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov under the registration number NCT05813132 ( https://clinicaltrials.gov/ct2/show/NCT05813132 ). (The first submitted registration date: is March 16, 2023).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Carboplatina , Citarabina , Etoposídeo , Transplante de Células-Tronco Hematopoéticas , Linfoma , Melfalan , Condicionamento Pré-Transplante , Transplante Autólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Feminino , Masculino , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Melfalan/uso terapêutico , Adulto , Linfoma/terapia , Linfoma/mortalidade , Linfoma/tratamento farmacológico , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carboplatina/uso terapêutico , Adulto Jovem , Adolescente , Resultado do TratamentoRESUMO
Myelodysplastic syndrome (MDS) is a very heterogeneous clonal disorder. Patients with "higher-risk" MDS, defined by specific recurrent genetic abnormalities, have a poor prognosis because of a high risk of progression to secondary acute myeloid leukemia with low chemosensitivity. Allogeneic hematopoietic stem cell transplantation remains the only treatment that offers durable disease control because the donor immune system allows graft-versus-MDS effects. In terms of preparation steps before transplantation, targeting the malignant clone by increasing the conditioning regimen intensity is still a matter of intense debate. MDS is mainly diagnosed in older patients, and high toxicity related to common myeloablative conditioning regimens has been reported. Efforts to include new drugs in the conditioning regimen to achieve the best malignant clone control without increasing toxicity have been made over the past 20 years. We summarized these retrospective and prospective studies and evaluated the limitations of the available evidence to delineate the ideal conditioning regimen.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Condicionamento Pré-Transplante , Humanos , Condicionamento Pré-Transplante/métodos , Síndromes Mielodisplásicas/terapia , Síndromes Mielodisplásicas/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante HomólogoRESUMO
Immunodeficiency-Centromeric instability-Facial dysmorphism (ICF) syndrome is an inborn error of immunity characterized by progressive immune dysfunction and multi-organ disease usually treated with antimicrobial prophylaxis and immunoglobulin substitution. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment, but data on outcome are scarce. We provide a detailed description of disease characteristics and HSCT outcome in an international cohort of ICF syndrome patients. Eighteen patients (including all four genotypes) were enrolled. Main HSCT indications were infections (83%), enteropathy/failure to thrive (56%), immune dysregulation (22%) and myelodysplasia/haematological malignancy (17%). Two patients underwent pre-emptive HSCT after early diagnosis. Patients were transplanted between 2003-2021, at median age 4.3 years (range 0.5-19), after myeloablative or reduced-intensity conditioning, from matched sibling or matched family donors, matched unrelated or mismatched donors in 39%, 50% and 12% of cases respectively. Overall survival was 83% (all deaths occurred within the first 5 months post-HSCT; mean follow-up 54 months (range 1-185)). Acute GvHD occurred in 35% of patients, severe (grade III) in two (12%), while none developed chronic GvHD. At latest follow-up (median 2.2 years (range 0.1-14)), complete donor chimerism was achieved in 15/17 surviving patients. All survivors demonstrated normalized T and B cell numbers. Immunoglobulin substitution independence was achieved in all but two patients. All survivors recovered from pre-transplant infections, enteropathy/failure to thrive and immune dysregulation. All three patients transplanted at young age (≤ 3 years), after early diagnosis, survived. The favourable clinical and immunological HSCT outcome in this cohort of patients supports the timely use of this curative treatment in ICF syndrome.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Pré-Escolar , Criança , Masculino , Feminino , Lactente , Adolescente , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/diagnóstico , Adulto Jovem , Síndromes de Imunodeficiência/terapia , Síndromes de Imunodeficiência/diagnóstico , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Doenças da Imunodeficiência Primária/terapia , Doenças da Imunodeficiência Primária/diagnósticoRESUMO
We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bussulfano , Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Condicionamento Pré-Transplante , Transplante Homólogo , Vidarabina , Humanos , Bussulfano/administração & dosagem , Bussulfano/uso terapêutico , Pessoa de Meia-Idade , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Vidarabina/análogos & derivados , Vidarabina/administração & dosagem , Vidarabina/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Feminino , Masculino , Transplante de Células-Tronco Hematopoéticas/métodos , Idoso , Condicionamento Pré-Transplante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , SeguimentosRESUMO
High-dose therapy followed by autologous hematopoietic cell transplant (AHCT) remains a viable consolidation strategy for a subset of patients with relapsed or refractory (R/R) lymphomas. BEAM (carmustine, etoposide, cytarabine, and melphalan) is widely recognized as the predominant conditioning regimen due to its satisfactory efficacy and tolerability. Nevertheless, shortages of carmustine and melphalan have compelled clinicians to explore alternative conditioning regimens. The aim of this study was to compare the toxicity and transplant outcomes following BEAM, CBV (carmustine, etoposide, cyclophosphamide), BuMel (busulfan, melphalan), and BendaEAM (bendamustine, etoposide, cytarabine, melphalan). We retrospectively analyzed data from 213 patients (CBV 65, BuMel 42, BEAM 68, BendaEAM 38) with R/R lymphomas undergoing AHCT between 2014 and 2020. Multivariate models were employed to evaluate toxicity and transplant outcomes based on conditioning type. Among grade III to IV toxicities, oral mucositis was more frequently observed with BuMel (45%) and BendaEAM (24%) compared to BEAM (15%) and CVB (6%, P ≤ .001). Diarrhea was more common with BendaEAM (42%) and less frequent with BuMel (7%, P = .01). Acute kidney injury was only found after BendaEAM (11%). Febrile neutropenia and infectious complications were more frequent following BendaEAM. Frequencies of other treatment-related toxicities did not significantly differ according to conditioning type. BendaEAM (odds ratio [OR] 3.07, P = .014) and BuMel (OR 4.27, P = .002) were independently associated with higher grade III to IV toxicity up to D+100. However, there were no significant differences in relapse/progression, nonrelapse mortality, progression-free survival, or overall survival among the four regimens. BuMel and BendaEAM were associated with a higher rate of grade III to IV toxicity. Carmustine-based regimens appeared to be less toxic and safer; however, there were no significant differences in transplant outcomes. The utilization of alternative preparative regimens due to drug shortages may potentially lead to increased toxicity after AHCT for lymphoma.
Assuntos
Carmustina , Citarabina , Transplante de Células-Tronco Hematopoéticas , Linfoma , Melfalan , Condicionamento Pré-Transplante , Transplante Autólogo , Humanos , Condicionamento Pré-Transplante/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Linfoma/tratamento farmacológico , Linfoma/terapia , Adulto , Carmustina/uso terapêutico , Estudos Retrospectivos , Citarabina/uso terapêutico , Melfalan/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Etoposídeo/uso terapêutico , Bussulfano/uso terapêutico , Resultado do Tratamento , Ciclofosfamida/uso terapêuticoRESUMO
Current consensus recommends hematopoietic cell transplantation (HCT) for patients with myelofibrosis with intermediate or high-risk disease and age of less than 70 years. However, a higher chronological age should not be prohibitive for the eligibility decision in general, acknowledging that current life expectancy for the general population aged 70 years is â¼15 years, and current numbers of patients transplanted at 70 years or older is steadily increasing. The following study aimed to evaluate characteristics and outcomes of HCT in 115 myelofibrosis patients aged 70 years or older. This is a retrospective multicenter study, using the German Registry for Stem Cell Transplantation and Cellular Therapy (DRST). Adult myelofibrosis patients were included who received HCT up until 2021. Patients with secondary leukemia were excluded. Main endpoints were HCT demographics over time and outcomes after HCT (including overall survival, relapse incidence, non-relapse mortality, and graft-versus-host disease/relapse-free survival). Numbers of HCT increased over the past decade, with a significant spike since 2019. Comorbidity status of transplanted patients improved over time, while reduced-intensity conditioning was the preferred HCT platform, especially in most recent years. The 3-year overall survival was 55% (95% confidence interval [CI], 44%-65%). The 1-year cumulative incidence of relapse was 7% (95% CI, 3%-13%) and the 1-year cumulative incidence of non-relapse mortality was 22% (95% CI, 14%-31%). The 3-year graft-versus-host disease and relapse-free survival was 37% (95% CI, 27%-47%). Driver mutation genotype (in particular, non-CALR/MPL genotype) appeared to be the only variable that was significantly and independently associated with better survival in multivariable analysis, whereas neither comorbidity index nor dose intensity of pre-transplant conditioning appeared to influence outcome. This study demonstrated feasibility of curative treatment with HCT for myelofibrosis aged 70 or older, with significant increases in HCT numbers and improved fitness of older adults over recent years.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Sistema de Registros , Humanos , Mielofibrose Primária/mortalidade , Mielofibrose Primária/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Idoso , Masculino , Feminino , Alemanha/epidemiologia , Estudos Retrospectivos , Transplante Homólogo , Condicionamento Pré-Transplante/métodos , Idoso de 80 Anos ou mais , Doença Enxerto-Hospedeiro/epidemiologiaRESUMO
Since the introduction of post-transplantation cyclophosphamide (PTCy), haploidentical hematopoietic stem cell transplantation (haploSCT) has become a real alternative for patients who lack other eligible donors. The standard graft-versus-host disease (GVHD) prophylaxis after PTCy has been a calcineurin inhibitor (CNI) plus mycophenolate mofetil (MMF) (up to day +35), but promising results with sirolimus (with or without MMF) and single-agent tacrolimus have been published recently. This multicenter retrospective study compared the outcomes of 372 adult haploSCT recipients who received conditioning with thiotepa, busulfan, and fludarabine (TBF), PTCy, and additional GVHD prophylaxis with 1 of 3 strategies: cohort A, single-agent tacrolimus (n = 222); cohort B, CNI + MMF (n = 49); or cohort C, sirolimus + MMF (n = 101). No differences among the 3 cohorts were found in terms of grade II-IV acute GVHD (20% in cohort A, 25% in cohort B, and 30% in cohort C) or grade III-IV acute GVHD (9%, 6%, and 15%, respectively) at 100 days; however, cohort A had the lowest incidence of overall chronic GVHD (24%, 47%, and 52%, respectively; P = .001) and moderate-severe chronic GVHD (13%, 35%, and 33%, respectively; P = .001). There were no differences in 3-year overall survival, progression-free survival, nonrelapse mortality, or relapse among the 3 cohorts. Overall, our study suggests that single-agent tacrolimus, CNI + MMF, and sirolimus + MMF GVHD prophylaxis lead to similar outcomes following haploSCT with TBF and PTCy, with a low incidence of grade III-IV acute GVHD, although possible differences in chronic GVHD require further investigation.