Vitamin C and D supplementation in acute myeloid leukemia.

Recent studies have highlighted the role of vitamin C and D in acute myeloid leukemia (AML). In 2018, we changed our practices to add both vitamins to the supportive care for all consecutive patients with AML undergoing intensive chemotherapy. In this study, we compared the outcomes of patients treated before and after this change in practice. From 2015 to 2020, 431 patients were included, 262 of whom received no supplementation and 169 of whom received vitamin supplementation. Vitamin C and vitamin D was administered from day 10 of chemotherapy until hematologic recovery from induction and consolidation. Most patients presented at diagnosis with low levels of vitamin C and D. Upon recovery from induction, vitamin D levels among the vitamin C/D group significantly increased compared with those at diagnosis, and pretransplant levels were significantly higher in the vitamin C/D group compared with the control group (median of 33 vs 19 ng/mL; P < .0001). During induction, the rates of bacterial or fungal infection, hemorrhage, or macrophage activation syndrome were lower in the vitamin C/D group, whereas there was no difference in response rate, relapse incidence, and overall survival (OS). However, the multivariate analysis for OS showed a significant interaction between vitamin C/D and NPM1 mutation, meaning that vitamin C/D supplementation was significantly and independently associated with better OS in patients with NPM1 mutations (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.30-0.90; P = .019) compared with patients with wild-type NPM1 (HR, 1.01; 95% CI, 0.68-1.51; P = .95). In conclusion, vitamin C/D supplementation is safe and could influence the outcomes of patients with AML undergoing intensive chemotherapy.

Multiple Severe Toxicities of L-Asparaginase and Their Innovative Management during Induction Therapy of Acute Lymphoblastic Leukemia in an Adult Patient.

L-asparaginase is a key chemotherapeutic agent in acute lymphoblastic leukemia (ALL). It is also known for multiple and severe specific toxicities, without consensual management. We report the case of a 51-year-old man treated with L-asparaginase for recently diagnosed T-cell ALL. During the treatment, he developed a coma due to multifactorial diffuse cerebral edema, by hepatic encephalopathy, cerebral venous thrombosis, and hyperammonemia, all linked to toxicity of L-asparaginase. Specific and innovative treatments were employed to manage these toxicities: supplementation with L-carnitine, thiamine, and pyridoxine for hepatic toxicity, perfusion of sodium benzoate to decrease ammonemia, and extrahepatic albumin-based dialysis sessions, along with anticoagulation. The patient improved within two weeks and is currently alive 13 months later, in first complete remission, without sequelae, on an alleviated chemotherapy regimen.

Emerging biological therapies to treat acute lymphoblastic leukemia.

INTRODUCTION: Various settings of acute lymphoblastic leukemia (ALL) represent unmet medical needs: first remission at high risk of relapse, such as persistent minimal residual disease (MRD); relapse/refractoriness (R/R); elderly patients. Biological therapies targeting widely-shared antigens of blast cells have entered the clinic in B-cell precursor (BCP)-ALL. Area covered: Results of phase II/III trials of monoclonal antibodies (MoAbs) and phase I/II trials of adoptive cell therapy by chimeric antigen receptor-engineered T cells (CAR-T cells) are presented. Rituximab, a naked anti-CD20 MoAb, improves the results of chemotherapy in Philadelphia chromosome-negative BCP-ALL. Inotuzumab ozogamicin, an anti-CD22 immunotoxin, yields complete remission (CR) rates of 80% in R/R patients and in elderly newly diagnosed patients. Blinatumomab, a bispecific anti-CD19 and anti-CD3 agent redirects effector T cells towards B leukemic cells, is approved in R/R patients (40% CR, duration 6 months) and under investigation in MRD+ CR patients (80% negativation). Autologous anti-CD19 CAR-T cells undergo proliferation and persistence in the recipient. In limited series, they salvage more than 80% of advanced patients. Cytokine-release syndrome, encephalopathy and B-cell aplasia are shared, to varying extents, by blinatumomab and CAR-T cells. Expert opinion: Despite technological, ethical and clinical issues, biological therapies are currently changing the paradigm of treatment in BCP-ALL, and seem promised to dramatic developments.

Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results.

All-trans retinoic acid (ATRA) plus anthracycline chemotherapy is the reference treatment of newly diagnosed acute promyelocytic leukemia (APL), whereas the role of cytosine arabinoside (AraC) remains disputed. We performed a joint analysis of patients younger than 65 years included in Programa para el Estudio de la Terapéutica en Hemopatía Maligna (PETHEMA) LPA 99 trial, where patients received no AraC in addition to ATRA, high cumulative dose idarubicin, and mitoxantrone, and APL 2000 trial, where patients received AraC in addition to ATRA and lower cumulative dose daunorubicin. In patients with white blood cell (WBC) count less than 10 x 10(9)/L, complete remission (CR) rates were similar, but 3-year cumulative incidence of relapse (CIR) was significantly lower in LPA 99 trial: 4.2% versus 14.3% (P = .03), although 3-year survival was similar in both trials. This suggested that AraC is not required in APL with WBC count less than 10 x 10(9)/L, at least in trials with high-dose anthracycline and maintenance treatment. In patients with WBC of 10 x 10(9)/L or more, however, the CR rate (95.1% vs 83.6% P = .018) and 3-year survival (91.5% vs 80.8%, P = .026) were significantly higher in APL 2000 trial, and there was a trend for lower 3-year CIR (9.9% vs 18.5%, P = .12), suggesting a beneficial role for AraC in those patients.