11 research outputs found
The CARâHEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL
CD19-directed CAR T-cell therapy with brexucabtagene autoleucel (brexu-cel) has substantially improved treatment outcomes for patients with relapsed/refractory mantle cell lymphoma (r/r MCL). Prolonged cytopenias and infections represent common and clinically relevant side effects. In this multicenter observational study, we describe cytopenias and infections in 103 r/r MCL patients receiving brexu-cel. Furthermore, we report associations between the baseline CAR-HEMATOTOX (HT) score and toxicity events, non-relapse mortality (NRM), and progression-free/overall survival (PFS/OS). At lymphodepletion, 56 patients were HTlow (score 0â1) while 47 patients were HThigh (score â„2). The HThigh cohort exhibited prolonged neutropenia (median 14 vs. 6âdays, pâ<â.001) and an increased rate of severe infections (30% vs. 5%, pâ=â.001). Overall, 1-year NRM was 10.4%, primarily attributed to infections, and differed by baseline HT score (high vs. low: 17% vs. 4.6%, pâ=â.04). HThigh patients experienced inferior 90-day complete response rate (68% vs. 93%, pâ=â.002), PFS (median 9âmonths vs. not-reached, pâ<â.0001), and OS (median 26âmonths vs. not-reached, pâ<â.0001). Multivariable analyses showed that high HT scores were independently associated with severe hematotoxicity, infections, and poor PFS/OS. In conclusion, infections and hematotoxicity are common after brexu-cel and contribute to NRM. The baseline HT score identified patients at increased risk of poor treatment outcomes
CAR T-cell therapy for follicular lymphoma and mantle cell lymphoma
Patients with relapsed and/or refractory (R/R) follicular lymphoma (FL) and mantle cell lymphoma (MCL) have a poor prognosis with anticipated short progression-free and overall survivals. Two CD19-directed chimeric antigen receptor T-cell (CAR T) therapies are approved in the United States for R/R FL, namely, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel. The results of ZUMA-5 and ELARA studies led to the approval of axi-cel and tisagenlecleucel, respectively, after demonstrating high overall (ORR) and complete response (CR) rates in this high-risk population of FL patients who had received a median of 3 (rangeâ=â2â4) and 4 (rangeâ=â2â13) prior lines of therapies, respectively. For instance, the ORR for ZUMA-5 was 94% (CRâ=â79%), and for ELARA, it was 86% (CRâ=â69.1%). Pertaining to MCL, brexucabtagene autoleucel is approved for R/R MCL based on results of the ZUMA-2 study. In the latter study, despite the fact that all R/R MCL patients had been exposed to prior Brutonâs tyrosine kinase inhibitors, the reported ORR was 91%, with 68% achieving a CR. These results undoubtedly demonstrate a strong efficacy of CAR T therapy in both R/R FL and MCL; yet, one must acknowledge the relatively short follow-up time of all aforementioned studies. Thus, longer follow-up showing durability of responses and long-term safety is definitely needed
Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies
International audienceHodgkin lymphoma is a highly curable disease. Although most patients achieve complete response following frontline therapy, key unmet clinical needs remain including relapsed/refractory disease, treatment-related morbidity, impaired quality of life and poor outcome in patients older than 60 years. The incorporation of novel therapies, including check point inhibitors and antibody-drug conjugates, into the frontline setting, sequential approaches, and further individualized treatment intensity may address these needs. We summarize the current treatment options for patients with classical Hodgkin lymphoma from frontline therapy to allogeneic hematopoietic stem cell transplantation and describe novel trials in the field
Systemic Mastocytosis: A Mimicker of Reactive Arthritis
Objectives. Illustration of a case of systemic mastocytosis mimicking reactive arthritis in the absence of an infectious etiology. Methods. Review of the patientâs medical records. Results. We report a case of systemic mastocytosis relapse, presenting with pancytopenia accompanied by knee monoarthritis, cystitis, and bilateral conjunctivitis occurring simultaneously at the same time interval within 2â4âdays, mimicking reactive arthritis in the absence of an infectious etiology. Conclusion. Our case demonstrated reactive arthritis features (triad of urethritis, conjunctivitis, and arthritis) without an infectious trigger but rather a relapse of mastocytosis. We should think outside the box when faced with such a clinical scenario in the absence of an infectious etiology. Paraneoplastic reactive arthritis is to be considered after excluding an underlying infection
Hematopoietic Recovery and Transfusion Needs after Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Adult Patients with Hematologic Malignancies
Impact of cyclosporine A concentration on acute graftâvsâhost disease incidence after haploidentical hematopoietic cell transplantation
International audienceOBJECTIVES: This retrospective study analyzed the impact of early cyclosporine A (CsA) initiation (day -3) on the risk of acute graft-vs-host disease (aGvHD) after haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplant cyclophosphamide.METHODS: Sixty-one consecutives patients who underwent Haplo-HCT were analyzed.RESULTS: At day +180, the cumulative incidences of grade II-IV and grade III-IV aGvHD were 39% and 18%, respectively. Patients having a lowest CsA concentration (<301 ng/mL; the cutoff value used to segregate the patients between low and high CsA concentrations) in the first week after Haplo-HCT had a significantly higher risk of grade II-IV aGvHD (P = 0.02), severe grade III-IV aGvHD (P = 0.03), cGvHD (P = 0.02), and extensive cGvHD (P = 0.04). In multivariate analysis, a higher CsA concentration (â„301 ng/mL) during the first week following Haplo-HCT was the only parameter significantly associated with a reduced risk of grade II-IV and grade III-IV aGvHD (RR = 0.21; P = 0.049 and RR < 0.001; P < 0.0001, respectively). We find no correlation between CsA concentration and relapse, non-relapse mortality, progression-free survival, GvHD-free and progression-free survival, or overall survival.CONCLUSIONS: CsA could be initiated early before Haplo-HCT with achievement of high CsA concentration to reduce the risk of aGvHD without any detrimental effect on relapse
Impact of Adding Antithymocyte Globulin to Posttransplantation Cyclophosphamide in Haploidentical Stem-Cell Transplantation
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Early Cardiac Toxicity Associated With Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation
International audienceBackgroundPost-transplant cyclophosphamide (PT-Cy) has become a standard of care in haploidentical hematopoietic stem cell transplantation (HSCT) to reduce the risk of graft-versus-host disease. However, data on cardiac events associated with PT-Cy are scarce.ObjectivesThis study sought to assess the incidence and clinical features of cardiac events associated with PT-Cy.MethodsThe study compared clinical outcomes between patients who received PT-Cy (n = 136) and patients who did not (n = 195), with a focus on early cardiac events (ECE) occurring within the first 100 days after HSCT. All patients had the same systematic cardiac monitoring.ResultsThe cumulative incidence of ECE was 19% in the PT-Cy group and 6% in the noâPT-Cy group (p < 0.001). The main ECE occurring after PT-Cy were left ventricular systolic dysfunction (13%), acute pulmonary edema (7%), pericarditis (4%), arrhythmia (3%), and acute coronary syndrome (2%). Cardiovascular risk factors were not associated with ECE. In multivariable analysis, the use of PT-Cy was associated with ECE (hazard ratio: 2.7; 95% confidence interval: 1.4 to 4.9; p = 0.002]. Older age, sequential conditioning regimen, and Cy exposure before HSCT were also associated with a higher incidence of ECE. Finally, a history of cardiac events before HSCT and ECE had a detrimental impact on overall survival.ConclusionsPT-Cy is associated with a higher incidence of ECE occurring within the first 100 days after HSCT. Patients who have a cardiac event after HSCT have lower overall survival. These results may help to improve the selection of patients who are eligible to undergo HSCT with PT-Cy, especially older adult patients and patients with previous exposure to Cy
Recommendations for diagnosis and treatment of methemoglobinemia
Methemoglobinemia is a rare disorder associated with oxidization of
divalent ferro-iron of hemoglobin (Hb) to ferri-iron of methemoglobin
(MetHb). Methemoglobinemia can result from either inherited or acquired
processes. Acquired forms are the most common, mainly due to the
exposure to substances that cause oxidation of the Hb both directly or
indirectly. Inherited forms are due either to autosomal recessive
variants in the CYB5R3 gene or to autosomal dominant variants in the
globin genes, collectively known as HbM disease. Our recommendations are
based on a systematic literature search. A series of questions regarding
the key signs and symptoms, the methods for diagnosis, the clinical
management in neonatal/childhood/adulthood period, and the therapeutic
approach of methemoglobinemia were formulated and the relative
recommendations were produced. An agreement was obtained using a
Delphi-like approach and the experts panel reached a final consensus
>75% of agreement for all the questions