To study the outcome of histologic transformation (HT) in a large prospective cohort of patients with follicular lymphoma (FL) who previously responded to immunochemotherapy.
After a median 6-year ...follow-up of 1,018 randomly assigned patients from the PRIMA trial, disease progression was observed in 463 patients, 194 of whom had histologic documentation.
Forty patients had histology consistent with HT, and 154 had untransformed FL (median time to recurrence, 9.6 v 22.8 months, respectively; P = .018). Thirty-seven percent of biopsies performed during the first year of follow-up showed HT corresponding to 58% of all HTs. Altered performance status, anemia, high lactate dehydrogenase level, "B" symptoms, histologic grade 3a, and high Follicular Lymphoma International Prognostic Index scores at diagnosis were identified as HT risk factors. Response (complete v partial) to immunochemotherapy or rituximab maintenance had no impact on the risk of HT. After salvage treatment, patients with HT had less frequent complete response (50.3% v 67.4%; P = .03) and more disease progression (28.2% v 9.6%; P < .001) than patients without HT. Estimated overall survival for the patients with HT was poorer (median, 3.8 v 6.4 years; hazard ratio, 3.9; 95% CI, 2.2 to 6.9). Autologous stem cell transplantation improved the outcomes of patients with HT (median overall survival, not reached v 1.7 years) but not of patients with persistent FL histology.
HT in patients with FL who previously responded to immunochemotherapy is an early event associated with a poor outcome that may deserve intensive salvage with autologous stem cell transplantation. These data emphasize the necessity for biopsy at the first recurrence of FL.
Rituximab improves progression-free survival (PFS) and time to next treatment (TTNT) when compared with the watch and wait strategy for patients with low-tumor burden follicular lymphoma (FL). ...Prolonged rituximab maintenance did not prolong TTNT, whereas it raises concerns about resources use and patient adhesion. Our aim was then to investigate the use of short rituximab maintenance using the subcutaneous (SC) route in patients with low-tumor burden FL.
Patients with histologically confirmed CD20
low-tumor burden FL were randomly assigned to receive either rituximab, 375 mg/m
once daily on D1, D8, D15, and D22, intravenous route (IV, control arm), or rituximab, 375 mg/m
, on day 1 (D1), IV followed by rituximab 1,400 mg total dose, SC once daily on D8, D15, and D22, with maintenance at months 3 (M3), M5, M7, and M9 (experimental arm). The primary end point was PFS. Secondary end points included safety, overall response rates, TTNT, and overall survival (OS).
Two hundred two patients with low-tumor burden FL were randomly assigned to the experimental (n = 100) or control arm (n = 102). The primary end point was met: the 4-year PFS was 58.1% (95% CI, 47.5 to 67.4) and 41.2% (95% CI, 30.6 to 51.6) in experimental and control arms, respectively (hazard ratio, 0.585 0.393 to 0.871;
= .0076). Complete response (CR) rates were 59.0% (95% CI, 48.7 to 68.7) in the experimental arm and 36.3% (95% CI, 27.0 to 46.4) in the control arm (
= .001). TTNT and OS were not significantly different. CR was associated with longer PFS and TTNT. High rituximab exposure during the first three months was independently associated with higher CR, PFS, and TTNT.
SC rituximab improves PFS for patients with low-tumor burden FL when used in induction followed by short maintenance. High rituximab exposure during the first 3 months after treatment initiation is, however, the only parameter influencing patient outcomes.
We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged ...65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression,
Ffluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively (
<0.0001). Neither the mantle cell lymphoma index, nor fluorodeoxyglucose-positron emission tomography nor Ki67 positivity (cut off of ≥30%) showed a prognostic impact for survival. Hematologic grade 3-4 toxicities were mainly neutropenia (51%), thrombocytopenia (35%) and lymphopenia (65%). Grade 3-4 non-hematologic toxicities were mainly fatigue (18.5%), neuropathy (15%) and infections. In conclusion, the tested treatment regimen is active as frontline therapy in older patients with mantle cell lymphoma, with manageable toxicity. Minimal residual disease status after induction could serve as an early predictor of survival in mantle cell lymphoma.
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Platelet components (PCs) are occasionally associated with adverse transfusion reactions (ATRs). ATRs can occur regardless of the type of PC being transfused, whether it is a single-donor apheresis ...PC (SDA-PC) or a pooled PC (PPCs). The purpose of this study was to investigate the proteins and dysregulated pathways in both of the main types of PCs.
The proteomic profiles of platelet pellets from SDA-PCs and PPCs involved in ATRs were analysed using the label-free LC-MS/MS method. Differentially expressed proteins with fold changes >|1.5| in clinical cases versus controls were characterised using bioinformatic tools (RStudio, GeneCodis3, and Ingenuity Pathways Analysis (IPA). The proteins were confirmed by western blotting.
The common primary proteins found to be dysregulated in both types of PCs were the mitochondrial carnitine/acylcarnitine carrier protein (SLC25A20), multimerin-1 (MMRN1), and calumenin (CALU), which are associated with the important enrichment of platelet activation, platelet degranulation, and mitochondrial activity. Furthermore, this analysis revealed the involvement of commonly dysregulated canonical pathways, particularly mitochondrial dysfunction, platelet activation, and acute phase response. This proteomic analysis provided an interesting contribution to our understanding of the meticulous physiopathology of PCs associated with ATR. A larger investigation would assist in delineating the most relevant proteins to target within preventive transfusion safety strategies.
Within platelet transfusion strategies, the two primary types of PCs predominantly processed in Europe, include (i) single donor apheresis PCs (SDA-PCs) from one donor and (ii) pooled PCs (PPCs). The current study used PCs from five buffy coats derived from five whole blood donations that were identical in ABO, RH1 and KEL1 groups. Both PC types were shown to be associated with the onset of an ATR in the transfused patient.
Several common platelet proteins were found to be dysregulated in bags associated with ATR occurrences regardless of the type of PCs transfused and of their process. The dysregulated proteins included mitochondrial carnitine/acylcarnitine carrier protein (SLC25A20), which is involved in a fatty acid oxidation disorder; calumenin (CALU); and multimerin-1 (MMRN1), which is chiefly involved in platelet activation and degranulation. Dysregulated platelet protein pathways for ATRs that occurred with SDA-PCs and PPCs could support the dysregulated functions found in association with those three proteins. Those common platelet proteins may become candidates to define biomarkers associated with the onset of an ATR from PC transfusions, including monitoring during the quality steps of PC manufacturing, provided that the results are confirmed in larger cohorts. This study enriches our knowledge of platelet proteomics in PCs under pathological conditions.
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•Apheresis and whole blood PCs contain proteins involved in transfusion complications.•Proteomic analysis of the 2 types of PC linked to Adverse Transfusion Reaction.•Three proteins were similarly dysregulated in PCs involved in ATR.•Platelet activation and mitochondrial dysfunction were dysregulated.•The physiopathology of ATRs after PC transfusion is better understood.•The physiopathology of PC involved in ATR is better understood.
Pathogen reduction of platelet concentrates may reduce transfusion-transmitted infections but is associated with qualitative impairment, which could have clinical significance with regard to platelet ...hemostatic capacity.
To compare the effectiveness of platelets in additive solution treated with amotosalen-UV-A vs untreated platelets in plasma or in additive solution in patients with thrombocytopenia and hematologic malignancies.
The Evaluation of the Efficacy of Platelets Treated With Pathogen Reduction Process (EFFIPAP) study was a randomized, noninferiority, 3-arm clinical trial performed from May 16, 2013, through January 21, 2016, at 13 French tertiary university hospitals. Clinical signs of bleeding were assessed daily until the end of aplasia, transfer to another department, need for a specific platelet product, or 30 days after enrollment. Consecutive adult patients with bone marrow aplasia, expected hospital stay of more than 10 days, and expected need of platelet transfusions were included.
At least 1 transfusion of platelets in additive solution with amotosalen-UV-A treatment, in plasma, or in additive solution.
The proportion of patients with grade 2 or higher bleeding as defined by World Health Organization criteria.
Among 790 evaluable patients (mean SD age, 55 13.4 years; 458 men 58.0%), the primary end point was observed in 126 receiving pathogen-reduced platelets in additive solution (47.9%; 95% CI, 41.9%-54.0%), 114 receiving platelets in plasma (43.5%; 95% CI, 37.5%-49.5%), and 120 receiving platelets in additive solution (45.3%; 95% CI, 39.3%-51.3%). With a per-protocol population with a prespecified margin of 12.5%, noninferiority was not achieved when pathogen-reduced platelets in additive solution were compared with platelets in plasma (4.4%; 95% CI, -4.1% to 12.9%) but was achieved when the pathogen-reduced platelets were compared with platelets in additive solution (2.6%; 95% CI, -5.9% to 11.1%). The proportion of patients with grade 3 or 4 bleeding was not different among treatment arms.
Although the hemostatic efficacy of pathogen-reduced platelets in thrombopenic patients with hematologic malignancies was noninferior to platelets in additive solution, such noninferiority was not achieved when comparing pathogen-reduced platelets with platelets in plasma.
clinicaltrials.gov Identifier: NCT01789762.
Les plaquettes des concentrés plaquettes (CP) destinés à la transfusion libèrent des molécules inflammatoires ; certains CP sont associés à des effets indésirables receveur (EIR), malgré la mise en ...œuvre de la leucoréduction. Le but de cette étude est de déchiffrer le profil protéomique des plaquettes dans les mélanges de CP (MCP) et les CP d’aphérèse (CPA) lorsqu’ils sont associés à l’apparition d’un EIR.
L’analyse protéomique semi-quantitative (LC-MS/MS Label-free) a été réalisée à partir de culots plaquettaires (3 MCP et 3 CPA), vs. des CP appariés et bien tolérés sur le plan clinique. L’analyse bioinformatique a permis de caractériser les protéines différentiellement exprimées (DE) (Fold Change>| 1.5 |) et les voies dérégulées entre les CP-EIR vs. les CP-témoins.
Parmi les 473 et 146 protéines DE identifiées dans les MCP et CPA, respectivement, trois protéines communes présentaient une dérégulation significative dans les deux types de PC étudiés : la SLC25A20 (Mitochondrial carnitine/acylcarnitine carrier protein) était diminuée, tandis que la MMRN1 (multimerin-1) et la CALU (calumenin) étaient systématiquement augmentées dans les CP-EIR, vs. leurs témoins correspondants. Un état inflammatoire et un dysfonctionnement mitochondrial ont été observés.
les plaquettes des CP impliquées dans un EIR présentaient un profil protéomique modifié avec altération du signalosome plaquettaire. Cette étude enrichit notre connaissance sur les poches des CP impliqués dans un EIR.
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