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This study aimed to identify patient groups in which myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens induced superior progression-free survival (PFS) in patients with acute myeloid leukemia (AML) in complete remission (CR) using a machine-learning approach. Our study included 3273 patients aged 40–69 with AML in CR. The patients were divided into training ( N  = 2020) and validation cohorts ( N  = 1253). We employed a machine learning-based group identification model in the training cohort. Subsequently, in the validation cohort, we estimated the impact of the optimal conditioning group compared with the non-optimal conditioning group on PFS using an inverse probability weight analysis. The developed model was consistent with the eight factors and combinations, and the high score suggested that RIC was more appropriate than MAC. In the validation cohort, 127 patients with high scores and who received RIC and 769 patients with low scores and who received MAC were categorized into the optimal conditioning group (896, 71.5%). The weighted hazard ratio for PFS was 0.73 (95% confidence interval: 0.57–0.94) in the optimal conditioning group compared with the non-optimal conditioning group ( P  = 0.016). In conclusion, we developed an easy-to-use model that helps the physician choose a patient-specific conditioning regimen for patients with AML in CR.

This study was designed to investigate the frequency and severity of oral mucositis in patients with acute myeloid leukemia after allogeneic hematopoietic cell transplantation, in relation to the type of conditioning used. Eighty patients diagnosed with acute myeloid leukemia were assigned to two groups based on the conditioning regimen used before transplantation. The intensity of oral inflammatory lesions induced by chemotherapy (oral mucositis) was evaluated according to a 5-point scale recommended by World Health Organization. Oral mucosa was investigated in all patients before the transplantation and during two subsequent stages of the post-transplantation procedure in relation to the conditioning regimen used. Mucositis in the oral cavity was observed in the majority of patients (66%) in the first week after transplantation, whereas the largest percentage of patients suffering oral lesions (74%) occurred in the second week after transplantation. A significantly higher percentage of patients with mucositis was observed in the group which underwent myeloablation therapy (74% of MAC and 50% of RIC patients in the first week; 83% of MAC and 53% of RIC patients in the second examination).The severity of mucositis after transplantation was higher in the MAC patients compared to the RIC patients. The highest mean value of the mucositis index was recorded in the second week in the MAC group (1.59). In AML sufferers receiving allo-HSCT, oral mucositis is a significant complication of the transplantation. This condition is more frequent and more severe in patients after treatment with myeloablation therapy.

The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD) neg pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P =0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC ( P =0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27–52) vs 35% (95% CI 27–44); P =0.62). Patients MRD pos pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P =0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P =0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P =0.057), but absence of pre-HCT TKI (HR 1.88; P =0.018), RIC (HR 1.891; P =0.054) and pre-HCT MRD pos (HR 1.6; P =0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD neg status is preferred pre-HCT.

Few studies have addressed the role of reduced-intensity conditioning (RIC) and non-myeloablative (NMA) regimens in older adults with Philadelphia acute lymphoblastic leukemia (Ph + ALL). The objective of this current study was to compare the outcomes of RIC/NMA versus TBI-based myeloablative (MAC) regimens in Ph + ALL patients older than 40 years old who underwent hematopoietic cell transplantation (HCT) in CR1. We used a freely available database from the CIBMTR. Transplants were performed between 2013 and 2017. With a median follow-up of 37.6 months, we have included 629 patients. We used propensity score weighting. Three-year OSs were 64% in the TBI-MAC group and 66% in the RIC/NMA group. OS was not different (HR = 0.92; p = 0.69). Three-year relapse incidences were 21.6% and 27.6% in the TBI-MAC and RIC/NMA groups. RIC/NMA was not associated with an increase in relapse rate (HR 1.02; p = 0.91). Three-year NRMs were 24.3% in the TBI-MAC group and 20.3% in the RIC/NMA group. RIC/NMA was not associated with superior NRM (HR 0.88; p = 0.57). In summary, we have shown that RIC/NMA regimens achieve outcomes comparable to TBI-based MAC in Ph+ ALL older patients in CR1 who may tolerate a TBI-based MAC regimen.

Mycosis fungoides (MF) is a major variant of primary cutaneous T-cell lymphoma (CTCL) characterized by infiltration of neoplastic T cells in the epidermis and dermis. This disease progresses gradually and rarely reaches an advanced stage. Once advanced, MF is nearly impossible to treat due to limited therapeutic options. However, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has recently emerged as a potential treatment. Among hematopoietic stem cell (HSC) sources, umbilical cord blood transplantation (UCBT) offers significant advantages. Despite its potential, there are challenges in applying UCBT to adults, and there are only a few reports on its use for MF. We report a Japanese case of advanced MF maintaining complete remission (CR) with UCBT and review previous cases of CTCL, including MF, treated with UCBT.

This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR)=0.7, P =0.02) translating into a trend for better overall survival (OS; HR=1.3; P =0.07). Grade II acute GVHD had no net impact on OS, while grade III–IV acute GVHD was associated with a worse OS (HR=0.4, P <0.0.001) owing to high risk of nonrelapse mortality (NRM; HR=5.2, P <0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR=0.72; P =0.07) translating into a better OS (HR=1.8; P <0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR=0.65; P =0.02) but also with higher NRM (HR=3.5; P <0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD ( P <0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR=0.65; P =0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD.

Langerhans cell histiocytosis (LCH) is a disease caused by clonal expansion of CD1a+/CD207+ cells and is characterized by organ involvement and dysfunction. Treatment of LCH in children is risk-adapted, and multisystem LCH requires systemic therapy. Although systemic treatments such as chemotherapy and BRAF/MEK inhibitors have improved the cure rate of LCH, disease reactivation rates remain 30%, and eventually some patients progress to relapse-refractory LCH. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a promising salvage treatment strategy for children with relapse-refractory LCH. However, many questions such as the efficacy and indications of allo-HSCT, as well as suitable conditioning regimen are still undetermined for children with LCH. This review aimed to provide an update on advances in allo-HSCT for LCH in children, including indications, stem cell sources, conditioning regimens, chimerism, transplant-related complications, outcomes, and treatment of relapse.

Reduced-intensity conditioning (RIC) regimens allogeneic hematopoietic stem cell transplantation (HSCT) was developed for older patients or those with poor functional status. Haploidentical donor was appropriate alternative donor for patients without matched donors or patients with emergency disease state. However, there was few studies report the outcomes of RIC regimen of anti-thymocyte globulin (ATG) based haploidentical HSCT. The selection of the appropriate RIC regimen based on age and comorbidities in ATG-based haploidentical HSCT remains poorly described. To investigate the safety and efficacy of RIC regimen ATG-based haploidentical HSCT in older or unfit patients. Additionally, to explore the potential factors that impact the prognosis of RIC regimen of ATG-based haploidentical HSCT. We included a retrospective cohort of 63 patients with hematologic malignant diseases who underwent their first RIC haploidentical HSCT from November 2016 to June 2022 at our institutions. The conditioning regimen involved fludarabine (Flu) 30 mg/m²/kg 6 days combined with busulfan 3.2 mg/kg 2 days (Bu2) or 3 days (Bu3). ATG-Fresenius (ATG-F) was administered 10 mg/kg in total, ATG-thymoglobulin (ATG-T) was administered 6 mg/kg in total. The median age of patients in the entire cohort was 60 (32–67) years with a median follow-up of 496 (83–2182) days. There were 29 patients with AML, 20 patients with MDS, and 14 patients with ALL. A total of 32 patients underwent Bu2 RIC haplo-HSCT and 31 patients were treated with Bu3 RIC haplo-HSCT. The 2-year overall survival (OS) and 2-year disease-free survival (DFS) in whole cohort were 67.7% (95% confidence interval [CI], 53.8 − 85.1%) and 61.4% (95% CI, 48.8 − 77.3%) respectively. The cumulative incidence rates of grades II to IV and grades III to IV acute graft-versus-host disease (aGVHD) in whole cohort were 15.8% (95% CI, 4.8 − 19.6%) and 9.7% (95% CI, 0.0 − 11.8%) respectively. The 2-year cumulative incidence of chronic GVHD was 34.0% (95% CI, 18.9 − 46.3%). The 2-year cumulative incidence rates of relapse (IR) and non-relapse mortality (NRM) rates in whole cohort were 27.5% (95% CI, 14.5 − 33.7%) and 11.6% (95% CI, 2.2 − 21.9%) respectively. The probability of 2-year OS were 60.2% (95% CI:42.5-85.3%) in Bu2 and 85.5%(95% CI:73.0-100%) in Bu3 group respectively(P = 0.150). The probability of 2-year DFS were 49.7% (95% CI:33.0-74.8%) in Bu2 and 72.6% (95% CI:55.5-95.5%) in Bu3 group respectively (P = 0.045). The 2-year IR of Bu2 group was significantly higher than Bu3 group (P = 0.045). However, the 2-year NRM were not significantly different between Bu2 and Bu3 group(P > 0.05). In multivariable analysis, RIC regimen of Bu3 had superior OS and DFS than Bu2 group respectively [HR 0.42, 95% CI 0.18–0.98; P = 0.044; HR 0.34, 95% CI 0.14–0.86; P = 0.022]. Besides, RIC regimen of Bu3 had lower IR than Bu2 group [HR 0.34, 95% CI 0.13–0.89; P = 0.029]. The RIC regimen of ATG-based haploidentical HSCT is a safe and effective treatment option for patients who are older or have poor functional status. In particular, a relatively high-intensity pre-treatment regimen consisting of Bu achieves significant improvements in OS and DFS, thus providing more favorable post-transplantation clinical outcomes.

Rescue chemotherapy or autologous stem cell transplantation (autoSCT) gives disappointing results in relapsed peripheral T-cell lymphomas (PTCLs). We have retrospectively evaluated the long-term outcome of 52 patients receiving allogeneic SCT for relapsed disease. Histologies were PTCL-not-otherwise specified ( n =23), anaplastic large-cell lymphoma ( n =11), angioimmunoblastic T-cell lymphomas ( n =9) and rare subtypes ( n =9). Patients were allografted from related siblings ( n =33, 64%) or alternative donors ( n =13 (25%) from unrelated and 6 (11%) from haploidentical family donors), following reduced-intensity conditioning (RIC) regimens including thiotepa, fludarabine and cyclophosphamide. Most of the patients had chemosensitive disease ( n =39, 75%) and 27 (52%) failed a previous autoSCT. At a median follow-up of 67 months, 27 of 52 patients were found to be alive (52%) and 25 (48%) were dead ( n =19 disease progression, n =6 non-relapse mortality (NRM)). The cumulative incidence (CI) of NRM was 12% at 5 years. Extensive chronic graft-versus-host disease increased the risk of NRM (33% versus 8%, P =0.04). The CI of relapse was 49% at 5 years, influenced by disease status at the time of allografting ( P =0.0009) and treatment lines ( P =0.007). Five-year overall survival and progression-free survival (PFS) were 50% (95% CI, 36 – 63%) and 40% (95% CI, 27 – 53%), respectively. The current PFS was 44% (95% CI, 30–57%). In all, 8 out of 12 patients (66%) who received donor-lymphocytes infusions for disease progression had a response. At multivariable analysis, refractory disease and age over 45 years were independent adverse prognostic factors. RIC allogeneic SCT is an effective salvage treatment with a better outcome for younger patients with chemosensitive disease.

Various reduced-intensity conditioning (RIC) regimens are used to decrease toxicity while providing comparable outcomes to myeloablative regimens. We compared toxicity and outcomes between two RIC regimens, fludarabine with melphalan (Flu-Mel) and fludarabine with treosulfan (Flu-Treo), retrospectively over a 10-year period in two donor groups, matched related donor (MRD)/matched unrelated donor (MUD) and haploidentical (Haplo) transplants. The study included 138 patients, of which 105 received MRD/MUD (Flu-Mel: 94, Flu-Treo: 11) and 33 Haplo (Flu-Mel: 17, Flu-Treo: 16) transplants. In the MRD/MUD group, 44 (47%) of patients who received Flu-Mel had grade 3/4 oral mucositis compared to 1 (9%) who received Flu-Treo ( P  = 0.02). Corresponding numbers in the Haplo group were 7 (41%) and 1 (6%). Grade 3/4 diarrhoea was more frequent with Flu-Mel than Flu-Treo in the Haplo group (41% vs 6%; P  = 0.039), but not the MRD/MUD group. Median follow-up time for all patients was 4.8 years. Five-year OS in the MRD/MUD group was 62% with Flu-Mel versus 53% with Flu-Treo ( P  = 0.0694). Similarly, 5-year OS was 41% with Flu-Mel and 28% with Flu-Treo ( P  = 0.770) in the Haplo group. Severe mucositis and diarrhoea were significantly less frequent with Flu-Treo than Flu-Mel. Flu-Treo provided comparable outcomes to Flu-Mel in all donor transplants.