Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496).

BACKGROUND: In an ECOG-ACRIN Cancer Research Group study (E1496), maintenance rituximab (MR) was reported to prolong progression-free survival (PFS) in comparison with observation (OBS) alone in patients with indolent lymphoma after induction chemotherapy. Here the long-term follow-up of the same patient cohort is presented. METHODS: Patients with indolent lymphoma received induction chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP). Patients with stable disease or a better response were then randomized to weekly rituximab (375 mg/m(2) × 4 doses) every 6 months for 2 years (MR) or to OBS. The primary endpoint was PFS; the secondary endpoints were overall survival (OS), response rate, and toxicities. RESULTS: Of the 387 patients who initially received CVP induction, 158 were randomized to MR, and 153 were randomized to OBS. After a median follow-up of 11.5 years, patients on MR had longer median PFS (4.8 years) than patients on OBS (1.3 years; hazard ratio [HR], 0.49; P < .0001). However, there was no difference in OS between MR and OBS (10-year OS, 67% vs 59%; median OS, 13.5 years vs not reached; HR, 0.91; P = .69). Other than MR, only minimal residual disease after induction therapy was significantly associated with PFS on multivariate analysis (HR, 0.71; P = .02). A low initial tumor burden, minimal residual disease, follicular histology, a low Follicular Lymphoma International Prognostic Index score, and female sex were associated with longer OS. There was no increase in the rate of second primary malignancies with MR vs OBS. CONCLUSIONS: With long-term follow-up, MR did not influence OS. The PFS benefit was maintained. MR should be considered optional for patients with indolent B-cell lymphoma. Cancer 2016;122:2996-3004. © 2016 American Cancer Society.

Profound autoimmune hemolysis and Evans syndrome in two asplenic patients with babesiosis.

BACKGROUND: Evans syndrome (ES) is characterized by the simultaneous or sequential presence of multiple autoimmune cytopenias. It is often secondary to rheumatologic disorders or lymphoid malignancies, but has not previously been associated with babesiosis. Here we present two cases of severe cytopenias in asplenic patients precipitated by active babesiosis. CASE REPORT: The first patient had a history of Hodgkin's lymphoma in remission and autoimmune hemolytic anemia (AIHA) treated by splenectomy 12 years prior who presented with severe AIHA and thrombocytopenia after Babesia infection. The second patient had a history of ES requiring splenectomy, which relapsed after Babesia infection. RESULTS: The complex presentation and medical histories of both patients made the diagnosis challenging. Both patients' cytopenias responded to therapy, although the use of immunosuppressive agents in patients with active hematologic infections was challenging and required a multidisciplinary approach. CONCLUSION: These two cases illustrate the possibility of babesiosis to not only reactivate ES in asplenic patients, but also precipitate increased levels of immune deregulation, potentially provoking ES, a phenomenon not previously reported.

Preclinical Medical Student Hematology/Oncology Education Environment.

To better prepare medical students to care for patients in today's changing health-care environment as they transition to continuing their education as residents, many US medical schools have been reviewing and modifying their curricula and are considering integration of newer adult learning techniques, including team-based learning, flipped classrooms, and other active learning approaches (Assoc Am Med Coll. 2014). Directors of hematology/oncology (H/O) courses requested an assessment of today's H/O education environment to help them respond to the ongoing changes in the education content and environment that will be necessary to meet this goal. Several recommendations for the improvement of cancer education resulted from American Association for Cancer Education's (ACCE's) "Cancer Education Survey II" including a call for medical schools to evaluate the effectiveness of current teaching methods in achieving cancer education objectives (Chamberlain et al. J Cancer Educ 7(2):105-114.2014). To understand the current environment and resources used in medical student preclinical H/O courses, an Internet-based, Survey Monkey®-formatted, questionnaire focusing on nine topic areas was distributed to 130 United States Hematology/Oncology Course Directors (HOCDs). HOCDs represent a diverse group of individuals who work in variably supportive environments and who are variably satisfied with their position. Several aspects of these courses remain relatively unchanged from previous assessments, including a predominance of traditional lectures, small group sessions, and examinations that are either written or computer-based. Newer technology, including web-based reproduction of lectures, virtual microscopes, and availability of additional web-based content has been introduced into these courses. A variety of learner evaluation and course assessment approaches are used. The ultimate effectiveness and impact of these changes needs to be determined.

Methotrexate encephalopathy: Two cases in adult cancer patients, who recovered with pathophysiologically based therapy.

BACKGROUND/OBJECTIVES: Neurotoxicity is a serious and sometimes fatal adverse effect that can occur following methotrexate treatment. We describe two adult patients with hematological malignancies with methotrexate encephalopathy who recovered with dextromethorphan therapy. RESULTS: Case 1: A 24-year-old male with acute lymphoblastic leukemia developed the acute onset of bilateral facial weakness and slurred speech after his first treatment with high-dose intravenous methotrexate. The clinical scenario and a head magnetic resonance imaging supported a diagnosis of methotrexate encephalopathy. Treatment with dextromethorphan was coincident with recovery. Case 2: A 65-year-old female with recurrent diffuse large B-cell lymphoma was treated with high-dose intravenous methotrexate. Two weeks after a cycle, she developed hypoactive delirium, marked lethargy, ocular ataxia, and a right-sided facial weakness. Within 2 days of starting dextromethorphan, there was improvement with clinical recovery. CONCLUSIONS: These two cases suggest that N-methyl d-aspartate receptor activation by homocysteine may play an important role in the pathogenesis of methotrexate neurotoxicity.

Consolidation therapy with subcutaneous alemtuzumab after fludarabine and rituximab induction therapy for previously untreated chronic lymphocytic leukemia: final analysis of CALGB 10101.

PURPOSE: To determine if alemtuzumab consolidation improves response rate and progression-free survival (PFS) after induction chemoimmunotherapy in previously untreated symptomatic patients with chronic lymphocytic leukemia. PATIENTS AND METHODS: Patients (n = 102) received fludarabine 25 mg/m(2) intravenously days 1 to 5 and rituximab 50 mg/m(2) day 1, 325 mg/m(2) day 3, and 375 mg/m(2) day 5 of cycle 1 and then 375 mg/m(2) day 1 of cycles 2 to 6; fludarabine plus rituximab (FR) administration was repeated every 28 days for six cycles. Three months after completion of FR, patients with stable disease or better response received subcutaneous alemtuzumab 3 mg day 1, 10 mg day 3, and 30 mg day 5 and then 30 mg three times per week for 5 weeks. RESULTS: Overall response (OR), complete response (CR), and partial response (PR) rates were 90%, 29%, and 61% after FR, respectively; 15% of patients were minimal residual disease (MRD) negative. Of 102 patients, 58 received alemtuzumab; 28 (61%) of 46 patients achieving PR after FR attained CR after alemtuzumab. By intent to treat (n = 102), OR and CR rates were 90% and 57% after alemtuzumab, respectively; 42% of patients became MRD negative. With median follow-up of 36 months, median PFS was 36 months, 2-year PFS was 72%, and 2-year OS was 86%. In patients achieving CR after FR, alemtuzumab was associated with five deaths resulting from infection (viral and Listeria meningitis and Legionella, cytomegalovirus, and Pneumocystis pneumonias), which occurred up to 7 months after last therapy. The study was amended to exclude CR patients from receiving alemtuzumab. CONCLUSION: Alemtuzumab consolidation improved CR and MRD-negative rates after FR induction but caused serious infections in patients who had already achieved CR after induction and did not improve 2-year PFS or survival.