-Context -The use of thiopurine drugs such as azathioprine and 6-mercaptopurine has become quite common in the treatment of inflammatory bowel disease, transplantation and acute leukemias. Despite their effectiveness, these drugs are capable of causing drug-induced toxicity with the risk of death by myelosuppression. It is now known that these complications occur because of genetic polymorphisms of the thiopurinemethyltransferase (TPMT) enzyme, responsible for its metabolism. Objective -To assess the prevalence of thiopurine methyltransferase polymorphisms in the population of Joinville, SC, Brazil. Methods -We analyzed the frequency of four main allelic variants of the TPMT gene in 199 blood donors from Joinville, from February to April 2010. Results -The normal allele ("wild-type") was found in 93.9% of subjects studied. TPMT variants were detected in 12 subjects (6.03%).Conclusions -From this study, it was estimated at 6% the risk of toxicity by the administration of azathioprine and 6-mercaptopurine to patients in Joinville.

Introduction: Combination of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) is the standard of care in frontline therapy for classic Hodgkin lymphoma (cHL). Since 2018, bleomycin shortages have been reported in Brazil, with severe consequences for cHL patients. In the private setting, many institutions chose to use A+AVD, in which bleomycin is replaced by brentuximab-vedotin, or to import bleomycin from vendors not registered at the national drug agency. For public institutions, however, these costly strategies are largely unattainable. Methods: We conducted a single-arm open-label study to evaluate the substitution of bleomycin with etoposide 100 mg/m2 on days 1 and 15 of every 28-day cycle (AEVD) in previously untreated cHL, at Hospital Municipal São José, in Joinville, Brazil. Here we present preliminary data on the safety and efficacy of this combination in a scenario of lack of approved treatment options for this patient population. Results: Twenty-five patients aged 18 or more with cHL diagnosed between June 2018 and November 2020 were included. Fourteen patients (56%) were male, with median age of 27 years (range: 18-66). Most patients were stage II (60%, n=15), presented with B symptoms (56%, n=14) and high lactate dehydrogenase (LDH, n=13, 52%). For stage III-IV (n=5), high-risk IPS was present in 3 patients (score >2; 60%). For localized disease (n=20), unfavorable features according to the GHSG were seen in 16 patients (n=80%). All patients received between 3 and 6 chemotherapy cycles, with no recorded adverse event requiring hospitalization, treatment interruption or discontinuation. PET-CT was performed solely outside of our institution. Eight patients had access to interim PET-CT, all with Deauville scores (DS) 1-3. Overall response rate was 96%, with one disease progression after 5 cycles. Seven patients had CT scan-alone end-of-treatment (EOT) assessment, with 5 complete responses (CR) and 2 partial responses (PR), with both PR patients sustaining remissions after 10 and 12 months. EOT assessment with PET-CT (n=18) resulted in DS 1-3 in 72% (n=13), 4 in 22% (n=4) and 5 in one (6%). All 5 patients with DS 4-5 underwent biopsy after EOT assessment, with confirmation of relapsed or refractory (RR) cHL in 4 cases (22 year-old, stage IV high-risk female with progressive disease; 65 year-old, stage III low-risk male with relapse 11 months after EOT; 26 year-old, stage II high-risk male with relapse 6 months after EOT; 25 year-old, stage II high-risk female with relapse 4 months after EOT). Two RR cHL patients (50%) had treatment delays exceeding 30 days due to psychosocial or financial impacts emerging from the COVID-19 pandemic. All RR cHL patients had access to salvage treatments. At a median follow-up of 16 months (range: 8-36), no death was recorded and 12-month progression-free survival probability was 86% (95%CI: 72%-100%). Conclusions: Drug shortages impacting chemotherapy treatments have been a recurring problem worldwide, most noticeably among cytotoxic agents without in-class validated substitutions, as is the case with bleomycin. AEVD, as a novel approach to newly diagnosed cHL, appears to be safe, feasible and highly active in a population composed mostly of high-risk patients. Figure 1 Figure 1. Disclosures Boettcher: Novartis: Speakers Bureau.

Context: COVID-19 has become the largest health crisis in recent history, with complex healthcare challenges in frontline and critical care settings or in assisting patients with chronic diseases and cancer. Hematologic malignancies (HM) represent an additional factor for severe COVID-19, and mortality rates of 21%–62% for HM patients have been reported. Objective: To assess the incidence and severity of COVID-19 among HM inpatients. Design: We performed a retrospective analysis of electronic health charts of inpatients at Hospital Municipal São José (HMSJ) in Joinville, Brazil. Setting: This one-year period was selected considering that the first COVID-19 case in Joinville was reported on March 13. Local transmission was initially uncommon. Patients or Other Participants: Diagnosis of HM under the WHO classification and hospital stay for more than 48 hours were required. One hundred seventeen consecutive HM inpatients and 152 consecutive inpatients in the one-year period before COVID-19 in Joinville were included. Intervention: No intervention was performed. Main Outcome Measures: Mortality and incidence of COVID-19, severe disease, and thrombotic events. Results: COVID-19 cumulative incidence for HM inpatients was 25%, with one COVID-19 positive test every 73 patient hospital days. Very likely nosocomial transmission was seen in 19 cases (66%). Chemotherapy was administered within 30 days of symptom onset in 19 patients (66%). Severe neutropenia and severe thrombocytopenia were seen in 10 (34%) and 13 (45%) patients, respectively. For HM inpatients with and without COVID-19, the most common diagnoses were acute leukemia (34% and 23%, respectively; p=0.23), lymphoma (28% and 34%; p=0.65), and multiple myeloma (10% and 18%; p=0.4) Severe COVID-19 was established in 22 patients (76%), with 16 (55%) intensive care unit (ICU) admissions and 19 deaths (66%). TEs were reported in six patients. Thrombocytopenia prevented anticoagulation in 11 patients (50%). In-hospital mortality was 66% for HM inpatients versus 32% for HM inpatients without COVID-19 (p=0.002) and 23% for pre-COVID-19 HM inpatients (p<0.001). Conclusions: Cumulative incidence of COVID-19 in HM inpatients and the higher mortality over this one-year period are very alarming. As vaccination efforts are currently in expansion worldwide, it is uncertain whether hospital care for HM will carry on without inpatient transmission. Collaborative studies reporting on COVID-19 outcomes of HM inpatients are needed to guide decisions in this population.

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