The bendamustine plus rituximab regimen is active against primary nodal marginal zone B-cell lymphoma.

Primary nodal marginal zone lymphoma (NMZL) is a rare disease. There is no current consensus on how to treat it. The bendamustine plus rituximab (BR) regimen is effective for the treatment of follicular and other indolent lymphomas, but its efficacy in NMZL is not known. We analyzed the outcome of 14 patients diagnosed with NMZL (median age 67 years) who were treated with 375 mg/m2 of rituximab on day 1 and 90 mg/m2 of bendamustine on days 1 and 2. The overall and complete response rates were 93% and 71%, respectively. Major toxicity (grade 3/4 neutropenia) occurred in 5% of treatment courses. After a median follow-up of 22 months (range: 18-55), the overall survival and the free survival rates were 100% and 93%, respectively. None of the patients showing a complete or partial response developed secondary myelodysplastic syndrome/acute myeloid leukemia. Bendamustine plus rituximab was found to be an active and well-tolerated regimen leading to the rapid control of disease.

Rituximab is an effective and safe treatment of relapse in elderly patients with resistant warm AIHA.

We evaluated the efficacy and safety of rituximab for the treatment of 23 elderly patients (median age 78 years) with warm autoimmune haemolytic anaemia (AIHA). The median follow-up was 31 months. Patients had received one to five previous treatments. Rituximab was administered by intravenous infusion at a dose of 375 mg/m(2) once weekly for 4 weeks. The OR rate was 86.9 % (CR = 39.1 %, PR = 47.8 %). Median OS was 87 months. The median OS of patients who reached CR could not be calculated, and that of patients with PR was 67 months. At last follow-up, eight of the 20 responding patients, including one patient in CR and seven in PR, had relapsed after a median of 6 months. Failure to achieve CR was a risk factor for relapse (p = 0.028). We did not identify any pretreatment characteristics predictive of response to rituximab. In conclusion, rituximab is an effective treatment for elderly patients with refractory warm AIHA.

R-CVP regimen is active in frail elderly patients aged 80 or over with diffuse large B cell lymphoma.

Patients aged 80 or over with diffuse large B cell lymphoma (DLBCL) often have comorbidities that increase drug toxicity and prevent the use of otherwise optimal treatment. We performed a retrospective analysis of 43 patients aged 80 or over (median age: 83; range: 80-93) unable to receive treatment with anthracyclines, at diagnosis of DLBCL, treated with an R-CVP treatment (standard R-CHOP without doxorubicin). The patients had one or more comorbidities: 18 patients (41.9 %) had a performance status (PS) of 3; 23 patients (53.5 %) had low creatinine clearance; 12 patients (27.9 %) had low left ventricular ejection fraction; seven patients (16.3 %) had poor hepatic function; and 26 patients (60.5 %) had a Charlson index score ≥4. Thirty patients (70 %) had two or three adverse factors according to the age-adjusted International Prognostic Index. Twenty-five patients (58.1 %) received eight cycles of R-CVP, but the full eight cycles could not be given to 18 patients (41.9 %). The OR rate was 58.1 % (CR 37.2 %). There were 34 deaths (79 %) during treatment and follow-up. Ten patients (23.3 %) died early from toxicity before interim evaluation; all had PS 3. The median follow-up of surviving patients was 52.6 months. The overall 2-year survival rate was 31.9 % and the median OS was 12.6 months. The median OS for patients who completed the entire treatment was 26.4 months. The median PFS was 11.2 months. In multivariate analyses, OS was only affected by performance status ≥2 and Charlson index score ≥4. The R-CVP regimen can be active in elderly frail patients aged 80 or more with DLBCL, but systematic geriatric assessment is required so that those unsuitable for chemotherapy are excluded.

Impact of the relative dose intensity on survival of patients with high-risk myelodysplastic syndromes treated with Azacitidine.

We performed a retrospective analysis of 93 myelodysplastic syndromes (MDS) patients with intermediate 2 or high-risk IPSS score to study the impact of Azacitidine (AZA) relative dose intensity (RDI) <80% on the overall survival (OS). There were 51.6% of patients who had full dose and 48.4% had dose reduction or delayed with a RDI <80%. Nineteen patients (20.4%) had RDI <80% before getting objective response. Overall and progression-free survivals (OS, PFS) probabilities for the whole population were 58% (95% CI: 48-69) and 47% (95% CI: 38-58) at 1 year; 35% (95% CI: 26-47) and 31% (95% CI: 23-43) at two years, respectively. When analyzing the outcomes according to the response to AZA, median OS was 32 months (range: 26-55) for responders and 8 months (range: 7-12) for nonresponders, with a respective 1-year and 2-year OS probabilities of 91% vs 28% and 66% vs 6%, respectively (P < 0.001). Interestingly, there was no impact of dose reduction on OS nor on PFS, however, when analyzing the timing of dose reduction as time-dependent variable, we found that patients who had dose reduction before achieving the objective response, had significantly lower OS (P = 0.02) and PFS (P = 0.01) compared to patients who had dose reduction after achieving the objective response. In multivariate analysis, acute myeloid leukemia with 21%-30% blasts in BM and poor and very poor karyotype significantly impacted OS, (HR = 2.09, 95% CI: 1.27-3.44, P = 0.004, and HR = 2.73, 95% CI: 1.6-4.6, P < 0.001 respectively), as well as PFS (HR = 1.84, 95% CI: 1.07-3.17, P = 0.028, and HR = 3.03, 95% CI: 1.7-5.39, P < 0.001, respectively).

Prognostic impact of elevated pretreatment serum ferritin in patients with high-risk MDS treated with azacitidine.

Iron overload has been associated with poor overall survival in patients with higher-risk myelodysplastic syndromes after allogeneic hematopoietic stem cell transplantation, but has not been investigated in higher-risk MDS patients treated with hypomethylating agents. We evaluated the prognostic value of serum ferritin levels at diagnosis in a retrospective analysis of 48 patients with an intermediate 2 or high-risk International Prognostic Scoring System (IPSS) score treated with azacytidine. overall survival probability at 1 and 2 years was 58% and 42%, respectively. When stratifying according to serum ferritin level at azacytidine initiation, patients with serum ferritin level <725 ng/mL had significantly better OS than those with serum ferritin level ≥725 ng/mL, with an overall survival probability of 74% (95% confidence interval [CI]: 58-94) versus 44% (95% CI: 28-68) at 1 year and 57% (95% CI: 39-81) versus 28% (95% CI: 15-52) at 2 years, respectively (p = 0.034). Median progression-free survival was 16.15 months (range: 9-26) for the entire cohort. Progression-free survival probabilities according to serum ferritin cut-off level <725 ng/mL or ≥725 ng/mL at 1 and 2 years were 70% (95% CI: 53-91) versus 44 (95% CI: 28-68) and 52% (95% CI: 35-77) versus 24% (95% CI: 12-48), respectively (p = 0.031). We have demonstrated that an serum ferritin level ≥725 ng/mL was associated with worse overall survival and progression-free survival when adjusting for other covariables in multivariate analysis, in addition, unfavorable karyotype led to worse outcome. In conclusion, we believe that that negative effect of serum ferritin level on overall survival is not only related to the iron toxicity, but most probably may also be considered as a surrogate marker for very ineffective erythropoiesis leading to marked anemia.

Quadri-lineage disease involving nodal B-cell marginal zone lymphoma, high-grade B-cell lymphoma, Kaposi's syndrome, and acute myeloid leukemia.

A patient with a marginal zone lymphoma received RCHOP and obtained PR. He received RDHAP, autograft, and obtained CR. Three months later, he developed Kaposi's sarcoma with spontaneous regression. Two months later, he developed DLBCL treated with R-MIV with CR. Thereafter, he developed AML and died a few days later.