Clinical Characteristics and Outcomes of Acute Lymphoblastic Leukemia in Adolescents and Young Adults in Malawi.

PURPOSE: There are limited data on treatment and outcomes for acute lymphoblastic leukemia (ALL) among adolescents and young adults in sub-Saharan Africa. We describe a prospective observational cohort in Malawi. METHODS: Patients age 15-39 years with newly diagnosed ALL at Kamuzu Central Hospital, Malawi, were enrolled from 2013 to 2019; follow-up was censored on December 2020. ALL diagnosis was confirmed on-site using immunohistochemistry and telepathology consultation involving pathologists in Malawi and the United States. All but four patients were treated with a modified pediatric-inspired regimen (Cancer and Leukemia Group B 10403 protocol). Key modifications included omission of asparaginase and no dose escalation for methotrexate. RESULTS: Of 19 participants, the median age was 22 (range 15-36) years. Of the 15 patients who initiated treatment, 11 (73%) achieved remission after induction, one (7%) died during induction, two (13%) had refractory disease, and one (7%) absconded. No patients were lost to follow-up. Eventually, 10 of 11 patients (91%) with confirmed remission relapsed. The median duration of first remission was 10 (range 3-22) months. Twelve of 15 treated patients (80%) had died at the time of censoring. Among treated patients, the 12- and 24-month overall survival was 50% (95% CI, 23 to 72) and 17% (95% CI, 3 to 42), respectively. CNS involvement was associated with worse survival. CONCLUSION: It is possible to treat adolescents and young adults with ALL in low-resource settings using a low-cost, pediatric-inspired regimen; however, outcomes are poor. Both cost and limitations in supportive care infrastructure limit intensive cytotoxic approaches such as asparaginase. Patient-reported outcomes are needed to understand the quality of life and cost-effectiveness. Critically, innovative, leap-frog therapies, such as monoclonal or bispecific antibodies, and feasible economic models for resource-limited settings are urgently needed.

Acute Thrombotic Microangiopathy and Cortical Necrosis Following Administration of Alemtuzumab: A Case Report.

Alemtuzumab, a humanized monoclonal antibody that targets CD52 antigens on lymphocytes and monocytes, has shown efficacy in preventing relapse in relapsing-remitting multiple sclerosis. Despite known severe (yet rare) renal side effects such as anti-glomerular basement membrane disease and membranous glomerulopathy, to our knowledge, alemtuzumab has never been documented to cause drug-induced thrombotic microangiopathy. We describe a 39-year-old woman with relapsing-remitting multiple sclerosis who developed acute kidney injury requiring renal replacement therapy after 1 dose of alemtuzumab, as well as microangiopathic hemolytic anemia and thrombocytopenia. Pathologic examination of a kidney biopsy specimen demonstrated extensive cortical necrosis and arteriolar fibrin thrombi with nonspecific immunofluorescence staining of immunoglobulin M and C3 and absence of immune deposits on electron microscopy. These findings were consistent with the diagnosis of acute thrombotic microangiopathy. She received dexamethasone and underwent plasmapheresis, which was unsuccessful at removing alemtuzumab. The patient received renal replacement therapy for approximately 7 weeks, followed by slow recovery of kidney function that returned close to her baseline.

Rasburicase in the management of tumor lysis: an evidence-based review of its place in therapy.

Tumor lysis syndrome (TLS) is a potentially life-threatening complication of cancer therapy characterized by two or more of the following laboratory abnormalities: hyperuricemia, hyperkalemia, hypocalcemia, and hyperphosphatemia, with resultant end-organ damage, eg, renal failure, seizures, or cardiac arrhythmias. High-risk patients include those with highly proliferative cancers and/or large tumor burdens, particularly in the setting of highly effective chemotherapy, among other risk factors. Before 2002, antihyperuricemic drug therapy was limited to allopurinol, a xanthine oxidase inhibitor. Rasburicase, a recombinant urate oxidase, was approved by the US Food and Drug Administration for children in 2002 and adults in 2009, ushering in a new era in TLS therapy. We attempted to critically appraise the available evidence supporting the perceived benefits of rasburicase in the management of TLS. A Medline search yielded 98 relevant articles, including 26 retrospective and 22 prospective studies of rasburicase for the treatment of TLS, which were then evaluated to determine the best available evidence for the effectiveness of rasburicase in terms of disease-oriented, patient-oriented, and economic outcomes. Rasburicase is now a standard of care for patients at high risk of TLS despite continuing debate on the correlation between its profound and rapid lowering of plasma uric acid levels with hard patient outcomes, eg, need for renal replacement therapy and mortality. Rasburicase is dramatically effective in lowering plasma uric acid levels. The mortality and cost-effectiveness benefits of this expensive drug remain to be conclusively proven, and well designed, randomized controlled trials are needed to answer these fundamentally important questions.