Background
Auto‐immune thrombotic thrombocytopenic purpura (TTP) is a morbid multi‐organ disorder. Cardiac involvement not recognized in initial disease descriptions is a major cause of morbidity. ...Therapeutic plasma exchange (TPE) requires exposure to multiple plasma donors with risk of transfusion‐transmitted infection (TTI). Pathogen inactivation (PI) with amotosalen‐UVA, the INTERCEPT Blood System for Plasma (IBSP) is licensed to reduce TTI risk.
Methods
An open‐label, retrospective study evaluated the efficacy of quarantine plasma (QP) and IBSP in TTP and defined treatment emergent cardiac abnormalities. Medical record review of sequential patient cohorts treated with QP and IBSP characterized efficacy by remission at 30 and 60 days (d) of treatment, time to remission, and volume (L/kg) of plasma required. Safety outcomes focused on cardiac adverse events (AE), relapse rates, and mortality.
Results
Thirty‐one patients (18 IBSP and 13 QP) met study criteria for auto‐immune TTP. The proportions (%) of patients in remission at 30 d (IBSP = 61·1, QP = 46·2, P = 0·570) and 60 d (IBSP = 77·8, QP = 76·9, P = 1·00) were not different. Median days to remission were less for IBSP (15·0 vs. 24·0, P = 0·003). Relapse rates (%) 60 d after remission were not different between cohorts (IBSP = 7·1, QP = 40·0, P = 0·150). ECG abnormalities before and during TPE were frequent; however, cardiac AE and mortality were not different between treatment cohorts.
Conclusions
Cardiac and a spectrum of ECG findings are common in TTP. In this study, IBSP and QP had similar therapeutic profiles for TPE.
There is no consensual first-line chemotherapy for elderly patients with mantle cell lymphoma (MCL). The GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang) group previously developed ...the (R)VAD+C regimen (rituximab, vincristine, doxorubicin, dexamethasone and chlorambucil), which appeared as efficient as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone) while less toxic. Based on this protocol, we now added bortezomib (RiPAD+C: rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil) given its efficacy in relapsed/refractory MCL patients. The goal of the current phase II trial was to evaluate the feasibility and efficacy of the RiPAD+C regimen as frontline therapy for elderly patients with MCL.
Patients between 65 and 80 years of age with newly diagnosed MCL received up to six cycles of RiPAD+C.
Thirty-nine patients were enrolled. Median age was 72 years (65–80). After four cycles of RiPAD+C, the overall response rate was 79%, including 51% complete responses (CRs). After six cycles, CR rate increased up to 59%. After a 27-month follow-up, median progression-free survival (PFS) is 26 months and median overall survival has not been reached. Four patients (10%) discontinued the treatment because of a severe toxicity and seven patients (18%) experienced grade 3 neurotoxicity.
The bortezomib-containing RiPAD+C regimen results in high CR rates and prolonged PFS with predictable and manageable toxic effects in elderly patients with MCL.
Rituximab, a chimeric mouse/human monoclonal antibody that binds to the CD20 antigen, is part of current treatment of many B-cell malignancies and several autoimmune diseases. Very few cases of ...rituximab administration during pregnancy have been described. We report here the case of rituximab administration during the first trimester of pregnancy in a woman with autoimmune hemolytic anemia. No significant effects were observed in B-cell counts or the immune status of the newborn.
Although Hizentra is indicated for immunoglobulin replacement therapy in patients with primary and secondary immunodeficiencies, phase III trials have focused on patients with primary ...immunodeficiencies. In this 9-month, real-life, prospective, non-interventional, longitudinal, multicenter study of patients with primary and secondary immunodeficiencies in France, treatment modalities (primary endpoint), efficacy, safety, tolerability, quality of life, and treatment satisfaction were evaluated using descriptive statistics.
Starting in January 2012, 117 patients were enrolled (99 adults, 18 children). Secondary immunodeficiencies were present in 48.7 % of patients. At follow-up, injections were administered every 7 days in 92.2 % of patients. Nine patients (7.8 %) were taking Hizentra every 10-14 days. The median dose of Hizentra administered was 0.1 g/kg/injection. Fifty-six patients were administered doses <0.1 g/kg/injection and 13 patients were administered doses >0.2 g/kg/injection. Mean trough IgG titers were 9.0 ± 3.3 g/L (median 8.3 g/L). The mean yearly rate of infection was 1.2 ± 1.9. Mean scores on the Short Form-36 physical and mental component summaries were 46.3 ± 10.0 and 46.6 ± 9.3, respectively. Scores on the Treatment Satisfaction Questionnaire for Medication ranged from 69.9 ± 19.9 to 88.3 ± 21.2 depending on the domain. Treatment with Hizentra was well tolerated. No single drug-related systemic reaction occurred in more than one patient and few local reactions were reported (n = 5).
Under real-life conditions and in a cohort that included patients with primary and secondary immunodeficiencies, treatment with Hizentra was effective and well tolerated and patients were generally satisfied with the treatment.
Imatinib combined with high-dose chemotherapy is now becoming the gold standard for treatment of Philadelphia chromosome-positive acute leukemias. However, in all studies imatinib dosage was tapered ...to 400-600 mg per day. We decided to initiate a clinical trial to evaluate an opposite strategy based on high-dose imatinib (800 mg per day) combined with a less intensive chemotherapeutic regimen (vincristine and dexamethasone), which we called the DIV induction regimen. Thirty-one patients (18 relapsing or refractory Ph+ acute lymphoblastic leukemias and 13 lymphoid blast crisis chronic myelogenous leukemias) were enrolled. Complete remission (CR) was obtained in 28 out of 30 assessable patients. The median bcr-abl/abl ratio after the induction course was 0.1%. Median time to neutrophil recovery was 21 days. Fungus infections were observed in six patients out of 31 and possibly related to dexamethasone. Neuropathy due to vincristine was noted in 14 cases. Nine out of 19 patients under 55 years received allogenic stem cell transplantation after a median time of 78 days post-CR. Patients older than 55 years experienced a 90% CR rate without additional toxicities, suggesting the DIV regimen may also be proposed as a front line therapy in older patients.
Acquired von Willebrand syndrome (AVWS) in the setting of Waldenström macroglobulinemia (WM) is a challenging condition. No real standard of care is recommended for these patients, although the ...therapeutic strategy should include a rapid approach to the emergency bleeding events and to the underlying malignant lymphoid disorder. We report here our experience treating three elderly patients with these concomitant hematologic entities. The use of a bortezomib-based chemotherapy regimen showed a good profile of tolerance and efficacy even in a long-term follow-up period. These patients were treated for several years before switching their therapy to idelalisib, a targeted oral therapy that inhibits phosphatidylinositol 3-kinase isoform-delta (PI3KD), which is part of the signaling pathway downstream B-cell receptor. This approach was well tolerated and efficacious, although some adverse effects were observed, particularly at hepatic levels, but were all reversible. The same profile of tolerance/efficacy was observed in one very old patient who received idelalisib as a first-line therapy. We think that bortezomib-based therapy could be considered in refractory patients with AVWS associated with WM.
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