The fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG) chemotherapy regimen is an alternative to anthracycline-based therapy for the treatment of acute myeloid leukemia for patients with pre-existing cardiac disease.

We conducted a retrospective study assessing FLAG (fludarabine, cytarabine, and granulocyte colony-stimulating factor) as first-line treatment in 56 newly diagnosed acute myeloid leukemia patients considered ineligible for anthracycline-based treatment due to advanced age, significant comorbidities, or pre-existing cardiac disease. The median age was 69 (21-80); 46% received FLAG for pre-existing cardiac disease and others due to age (32%), non-cardiac comorbidities (20%), or previous anthracycline exposure (2%). The induction mortality was 16% and, among evaluable patients, 48% achieved a complete remission after the first induction course with an additional patient achieving a remission after a second course for a total complete remission rate of 50%. Four patients proceeded to an allogeneic stem cell transplant including two with pre-existing cardiac disease. Among non-transplanted patients, the relapse rate (RR) was 47%. When censored at time of stem cell transplant, the median relapse-free survival was 14.7 months. The median overall survival was 9.3 months with 1- and 2-yr survivals of 44% and 22%, respectively. There was no difference in clinical outcomes between patients treated with FLAG for cardiac reasons vs. other reasons. In conclusion, FLAG is a useful alternative to anthracycline-based induction for Acute myeloid leukemia in those with significant comorbidities including pre-existing cardiac disease.

Geographic disparities in the care and outcomes in adult chronic immune thrombocytopenia.

INTRODUCTION: Despite expert-based recommendations, real-world adherence to immune thrombocytopenia (ITP) guidelines is unclear. The impact of geographic and socioeconomic disparities on the quality of care and outcomes is unknown. We sought to determine the association between geographic remoteness and material deprivation on ITP care and outcomes. METHODS: We conducted a multi-centre retrospective cohort study of adults with chronic ITP requiring a second-line therapy between 2012 and 2019 in the province of Alberta, Canada. Socioeconomic status was measured using the Pampalon material deprivation index quintiles. Geographic disparities were assessed by the driving distance to a major centre, with geographic remoteness defined as >200 km from major centre. We examined the impact of geographic and material deprivation on quality of care, resource utilization (hospitalizations, transfusions), and outcomes (major bleeding, all-cause mortality and ITP-related mortality). Cox proportional hazards models were used to examine the impact of geographic remoteness, rural residence and material deprivation on overall survival and ITP-related survival. RESULTS: We included 326 ITP patients, median age of ITP diagnosis was 57 years, 182 (56 %) were female. Most patients (58 %) lived within 20 km of a major centre, whereas 49 (15 %) lived in a geographically remote area (>200 km). Geographic remoteness was significantly associated with material deprivation and lower likelihood of management by hematologists (84 % vs 99 %, P = 0.0001). It was also associated with lower rates of hepatitis C (71 % vs 89 %, P = 0.005) and hepatitis B testing (69 % vs 86 %, P = 0.03), and a non-significant trend towards lower rates of HIV testing (73 % vs 83 %, P = 0.051) compared with those <20 km from a major centre. Incomplete hyposplenic vaccinations among splenectomized patients (52 %), early splenectomy within 12 months of ITP diagnosis (35 %), inappropriate platelet transfusions (41 %), and inappropriate hospitalizations for asymptomatic thrombocytopenia (16 %) were common regardless of geographic distribution. There were 28 (9 %) ITP-related deaths (major bleeding or infections), most occurred within the first year of ITP diagnosis. Material deprivation, but not geographic remoteness, was an independent predictor of all-cause mortality (aHR 1.9, 95 % CI 1.1-3.3 in the most deprived quintile vs least deprived quintile). Rural residence trended towards increased hazard of ITP-related deaths (aHR 1.7, 95 % CI 0.9-3.2). CONCLUSION: We demonstrated substantial deviations of ITP care from consensus guidelines, and geographic disparities in access to care and diagnostic workup. Future quality improvement initiatives are critical to improve the quality of care and reduce inequities.

Treatment patterns and outcomes of second-line rituximab and thrombopoietin receptor agonists in adult immune thrombocytopenia: A Canadian retrospective cohort study.

BACKGROUND: The optimal choice of second-line treatment for immune thrombocytopenia (ITP) is unclear. Guidelines recommend either rituximab, splenectomy, or thrombopoietin receptor agonists (TPO-RA). There is, however, scarce data comparing treatment patterns, outcomes and resource utilization across second-line treatments. Despite Canada's universal healthcare system, publicly funded access to second-line ITP therapies is highly variable across provinces/territories. OBJECTIVES: To describe treatment patterns and compare health service utilization and outcomes among recipients of second-line rituximab and TPO-RA for ITP. METHODS: In this multicentre retrospective cohort study, we included adults who received second-line ITP therapies rituximab, eltrombopag and romiplostim (2012-2020) in Alberta, Canada. Patients were identified through a provincially-funded special drug access (STEDT) program. We examined treatment patterns, predictors of second-line treatment, hospitalizations, blood product utilization, and outcomes. Kaplan-Meier survival curves were used to estimate the cumulative incidence of ITP-related hospitalizations (bleeding or infections), overall survival (OS) and relapse-free survival (RFS). Cox proportional hazards regression was used to examine the impact of second-line therapy on OS. RESULTS: 223 patients received rituximab (67 %), eltrombopag (29 %), and romiplostim (4 %). TPO-RA recipients experienced significantly longer time from ITP diagnosis to second-line therapy compared with rituximab recipients (15.9 vs 6.7 months, P < 0.0001), accompanied by significantly higher platelet and IVIG utilization prior to second-line therapy. Age (adjusted odds ratio [aOR] 1.04, 95 % CI 1.02-1.07, P < 0.0001) and prior intracranial hemorrhage (aOR 12.7, 95 % CI 1.6-272.8, P = 0.03) were significant predictors of second-line TPO-RA. TPO-RA is associated with a trend towards longer median RFS (6.3 vs 3.8 years, P = 0.06) compared with rituximab, and similar rates of ITP-related hospitalizations, major bleeding, and thromboembolism. Age, time period, and Charlson comorbidity index, but not second-line ITP therapy, were significant predictors of OS. CONCLUSIONS: Our study identified older age and intracranial hemorrhage as predictors of second-line TPO-RA prescription in a real-world practice. There were no significant differences in hospitalizations and outcomes between second-line rituximab and TPO-RA, although delayed initiation of TPO-RA was associated with higher blood product utilization.

Case Series of 3 Patients Diagnosed With Atypical Hemolytic Uremic Syndrome Successfully Treated With Steroids, Plasmapheresis, and Rituximab.

RATIONALE: Atypical hemolytic uremic syndrome, which has a high probability of chronic kidney disease, morbidity, and mortality, needs to be promptly recognized when patients present with microangiopathic hemolysis. PRESENTING CONCERNS OF THE PATIENT: Three patients present with laboratory parameters consistent with a thrombotic microangiopathy. With a suspected diagnosis of thrombotic thrombocytopenic purpura, steroids with plasmapheresis were initiated. DIAGNOSES: With ADAMTS13 levels reported normal, the suspected diagnoses were reevaluated. Given ongoing renal impairment, atypical hemolytic uremic syndrome was strongly considered. INTERVENTIONS: When local funding issues precluded the prompt use of eculizumab, 4 doses of weekly rituximab were trialed. OUTCOME: Over 2 years later, all 3 patients have sustained durable remissions defined by the absence of kidney impairment or laboratory investigations concerning for microangiopathic hemolytic relapse. LESSONS LEARNED: In cases of a suspected autoimmune mechanism leading to atypical hemolytic uremic syndrome, long-term use of eculizumab may not be required.

EXPOSITION: Le syndrome hémolytique et urémique atypique (SHUa), une affection qui présente une forte probabilité d'évolution vers l'insuffisance rénale chronique et vers un risque accru de morbidité et de mortalité. Conséquemment, il devrait être soupçonné promptement lorsqu'un patient montre des signes cliniques d'une hémolyse microangiopathique. PRÉSENTATION DES CAS: L'étude présente le cas de trois patients dont les paramètres de laboratoire laissaient présager une microangiopathie thrombotique. Un diagnostic de purpura thrombocytopénique thrombotique étant soupçonné, un traitement stéroïdien avec plasmaphérèse a été initié. DIAGNOSTIC: Les taux d'ADAMTS13 s'étant avérés normaux, le diagnostic présumé a dû être réévalué; la présence d'une défaillance rénale persistante a permis d'aiguiller le diagnostic vers le syndrome hémolytique urémique atypique. INTERVENTIONS: Des problèmes de financement local ayant empêché l'utilisation rapide de l'eculizumab, on a plutôt mis à l'essai un traitement consistant en quatre doses hebdomadaires de rituximab. RÉSULTATS: Plus de deux ans plus tard, les trois patients connaissent une rémission durable, définie par l'absence d'insuffisance rénale ou par des résultats de laboratoire indicateurs d'une rechute hémolytique microangiopathique. LEÇON TIRÉE: Dans les cas où on soupçonne la présence d'un mécanisme auto-immun pouvant entraîner un syndrome hémolytique urémique atypique, le recours à un traitement de longue durée par l'eculizumab n'est pas forcément nécessaire.

Incremental value of the bone marrow trephine biopsy in detecting residual leukemia following treatment for Acute Myeloid Leukemia.

Most guidelines suggest that only the bone marrow aspirate (BMA) is necessary to assess residual disease following intensive chemotherapy for Acute Myeloid Leukemia (AML) with the bone marrow trephine biopsy (BMTB) recommended in cases of a poor quality BMA. We performed a retrospective study evaluating this in a cohort of patients receiving intensive chemotherapy for AML. Residual disease was assessed by morphological examination of the BMA and BMTB±immunohistochemistry. Of the 647 marrows 32.6% were interim marrows performed prior to peripheral count recovery, 41.7% were end of induction (EOI) marrows and the remaining were 'other marrows'. The BMA and BMTB findings were concordant in 92.8% of cases. The BMTB led to a change in diagnosis from 'no leukemia' to 'residual leukemia' in 5.2% of interim, 3.7% of EOI and 2.4% of 'other' marrows. The BMA alone had a sensitivity of 86.8% in detecting residual leukemia and of 82.3%, 82.5% and 94.2% for interim, EOI and 'other marrows', respectively. Despite the high concordance between the BMA and the BMTB the poor sensitivity of the BMA in detecting residual leukemia, particularly at EOI, may lead to an overestimation of the complete remission rates which may have therapeutic and clinical trial implications.

Delayed Hemolysis After Parenteral Artesunate Therapy for Severe Malaria in Two Returning Canadian Travelers.

Delayed hemolysis after parenteral artesunate has been described in Europe and Asia, but until recently had not been reported in patients receiving the artesunate product used in the United States and Canada. We report two cases of severe delayed hemolysis after the treatment with intravenous artesunate in Canada.