The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case ...for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.
Relapse is the leading cause of treatment failure for myeloid malignancies treated with allogeneic hematopoietic stem cell transplantation. Treatment options are very limited and use of azacitidine ...is one of the available options.
This was a retrospective, single-institution study. Of 28 evaluated patients, 18 were males, and the median age was 60 years (range, 15–78). There were 15 patients with acute myeloid leukemia, 8 with myelodysplastic syndrome, 4 with chronic myelomonocytic leukemia, and 1 with primary myelofibrosis. Ten patients received azacitidine for overt relapse, 14 received it as a preemptive therapy, and 4 others received it as maintenance treatment after allo-hematopoietic cell transplant (HSCT). Eleven patients received a donor lymphocyte infusion (DLI).
The patients received median 5 (1–9) cycles of azacitidine in preemptive and maintenance therapy and median 2.5 (1–9) cycles in patients with relapse. Thirty-nine percent of patients received DLIs. Median overall survival was 6.1 months (95% CI, 0.7–13) for relapse therapy vs 21.2 months (95% CI, 8.4-inf) for preemptive therapy. Among patients treated for relapse, 30% achieved temporary disease control and underwent the second allo-HSCT. A complete, cytogenetic remission was achieved in 50% of patients and stable minimal residual disease in 14% of patients in a group with preemptive therapy. Toxicity was considerable; neutropenia (71%), anemia (14%), thrombocytopenia (36%), and serious infections (36%) were observed in the preemptive setting.
These data support the notion that azacitidine is best used as a preemptive therapy against relapse for patients after allo-HSCT performed for myeloid malignancy. Applying azacitidine as therapy for ongoing relapse after allo-HSCT may lead to stable disease and allow for better performance of the second allo-HSCT.
•Treatment options for patients relapsing after allo-HSCT are limited.•Effectiveness of azacitidine was analyzed for prevention and treatment of relapse.•Azacitidine is best used as preemptive therapy against relapse.•Applying azacitidine in the therapy for ongoing relapse may lead to stable disease status.
High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) remains the mainstay of treatment of eligible patients diagnosed multiple myeloma. The role of ...clonal plasma cell (CPC) contamination was found as a reason for relapse, but results in terms of survival, progression, and purging were ambiguous. Therefore, the aim of the study was to explore the influence of CPC contamination in the autograft on survival and progression after auto-PBSCT.
The study included 59 patients diagnosed and treated for multiple myeloma in 1998–2004. Cells with coexpression of CD38+++CD138++CD56+ and lacking the expression of CD45, CD19, CD10, CD20, and CD23 were considered CPC in flow cytometry.
The risk of death and progression after auto-PBSCT increased significantly by 10% (P < .021) and 8% (P < .034) per 1 × 106/kg of the CPC number, respectively. For CPC number above 2.96 × 106/kg overall survival achieved clinical significance. Two years after auto-PBSCT, the risk of death was independent of CPC number among the patients who survived (P = .70). Analogous conclusions concerned results of progression-free survival at 1 year after auto-PBSCT.
High clonal plasma cell contamination (>2.96 ×1 06/kg; 90th percentile of CPC number) is associated with the worst progression-free survival and overall survival. Therefore purging in vitro might be considered for the patients with the highest CPC contamination. Negative consequences of CPC contamination on the risk of death are observed for only 2 years after auto-PBSCT. Thereafter only those patients who had lower CPC contamination survived.
•The finding that plasma cell contamination affects the risk of death and progression only in the first 2 years from auto-PBSCT confirms the harmful impact of clonal plasma contamination.
Abstract Background Although rhinosinusitis constitutes a major clinical problem in general population, data on rhinosinusitis in patients undergoing allogeneic hematopoietic stem cell ...transplantation (alloHSCT) are scarce. Therefore, the aim of the study was to assess the frequency of rhinosinusitis, the impact of rhinosinusitis on post-alloHSCT outcome, and to analyze risk factors potentially predisposing to rhinosinusitis. Methods Retrospective analysis of acute leukemia patients undergoing alloHSCT. Results A total of 87 patients (49 male), with a median age of 36 years (range, 18–58), transplanted from 1999 to 2010, were enrolled; 61 patients suffered from acute myeloid leukemia (AML) and 26 of acute lymphoblastic leukemia (ALL). Fifteen patients (17.2%) experienced rhinosinusitis before transplantation, among whom 5 (33%) experienced rhinosinusitis after alloHSCT; 22 patients (25.3%), 12 AML and 10 ALL, experienced rhinosinusitis after alloHSCT. The median time to rhinosinusitis was 200 days (range, 1–2,044). 11 patients experienced rhinosinusitis during the 1st 100 days after transplantation, 8 during the 1st 30 days. Post-alloHSCT rhinosinusitis did not affect overall survival of transplant patients ( P = .35). In univariate analysis only total body irradiation as part of conditioning (odds ratio OR, 2.78; 95% CI, 1–7.77) and previous nasal packing (OR, 5.18; 95% CI, 1.22–23.43) were associated with higher incidence of rhinosinusitis. In multivariate analysis, none of the analyzed parameters was shown to have an impact on rhinosinusitis development. Conclusions Rhinosinusitis is a frequent medical condition in patients undergoing alloHSCT. The overall survival of patients developing rhinosinusitis after HSCT is similar to survival of patients who do not. No risk factors for developing rhinosinusitis could be identified.
Background:
Hemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) is a rare syndrome of uncontrolled inflammation, where cytokine storm leads to a complex clinical picture with bone ...marrow failure, fever, hyperferritinemia and splenomegaly. These, along with other abnormalities and subsequent complications, cause a high mortality rate. Although several attempts to find prognostic variables were made, so far a complex model for survival in HLH has not been established.
Aims:
Aim of this project was to establish a statistical model predicting the risk of death after 6 months based on the data from the one of the largest European adult HLH patient cohorts.
Methods:
Data of 97 adult (≥ 18 years of age) patients with newly‐diagnosed HLH (from the HLH in Adults Database affiliated with PALG – Polish Acute Leukemia Group) were utilized to construct a prognostic model predicting the risk of death within 6 months from diagnosis. First, two alternative approaches were used: LASSO regression (allowing to select variables important for prognosis) and random forest (finding non‐linear relationships). Model performance was evaluated by repeated cross‐validation. Then, model explanation methods were used to build an improved model. R software (R Core Team, Vienna, Austria, version 3.5.1) was utilized.
Results:
Among 97 patients, a slight male predominance was observed (62%, 60/97). Median age at diagnosis was 39 (18–82). 43 (44%) patients survived at least 6 months from diagnosis, while 48 patients (49%) died in this period. HLH was triggered by the following factors: malignancy in 39, infection in 20, and autoimmune disease (MAS syndrome) in 19 patients. In another 19 patients cause of HLH could not be determined. LASSO regression and random forest achieved 76% and 70% cross‐validated AUC (Area under the ROC curve), respectively. With variables chosen by LASSO and dependencies discovered by random forest, a logistic regression model based on dichotomized features was created. This model achieved 76% cross‐validated AUC with improved accuracy. According to the model, the most important prognostic factor protecting from death is MAS syndrome (OR = 0.04 95% CI: 0.01–0.38). Among the other variables included in the model platelet count >50 G/l (OR = 0.35 0.13–0.96), total bilirubin <1 mg/dl (OR = 0.36 0.13–1) and Hb > 9 g/dl (OR = 0.42 0.14–1.24) are the most noteworthy.
Summary/Conclusion:
Constructed model can help in predicting prognosis of the adult HLH patients. The most important established prognostic factors are MAS syndrome as a triggering factor, total bilirubin, and platelet count with hemoglobin concentration (reflecting the severity of bone marrow failure).
PDF
