Intermediate dose cytarabine improves survival and relapse-free rate compared with standard-dose cytarabine as post-remission treatment for acute myeloid leukemia: A retrospection study.

ABSTRACT: The exact dose of cytarabine still remain controversial for the management of patients with acute myeloid leukemia (AML) after complete remission (CR), but recent studies favor lower doses. This study aimed to investigate the toxic effects of single-intermediate dose (ID) cytarabine in patients with AML after achieving CR, compared with standard-dose cytarabine.In this retrospective study, AML patients who achieved CR after consolidation therapy before enrollment between 07/2008 and 05/2019 were included. All patients were divided into single-ID cytarabine and standard-dose cytarabine. The Kaplan-Meier method was used to compare overall survival (OS) and relapse-free time (RFS). Cox regression models were used to assess factors independently associated with OS and RFS. The toxic side effects of hematology and non-hematology were observed.52 patients were enrolled. There were 33 in ID group, 19 in Standard dose group. The 3-year RFS rate (40.4% vs 22.2%, P = .031) was better in the ID group than in the standard-dose group, while the 3-year OS rate was not different between the 2 groups (50.2% vs 27.8%, P = .074). Treatment stratage of ID cytarabine chemotherapy significantly improve the prognosis of AML regardless of patient age, risk grade, WBC count. There were no significant differences between the 2 groups in grade 3 to 4 bone marrow suppression, gastrointestinal symptoms, blood transfusion, infections.Patients with AML receiving ID cytarabine showed better survival and similar toxicity profiles compared with patients who received standard-dose cytarabine.

Outcomes for Patients With Acute Promyelocytic Leukemia in South Africa.

BACKGROUND: The characteristics and outcomes of patients with acute promyelocytic leukemia (APL) from sub-Saharan Africa have not been published. PATIENTS AND METHODS: We report retrospectively on consecutively diagnosed APL patients treated in Cape Town, South Africa, during 1998-2019. A total of 69 patients were treated, of whom 27 (39%) were classified as having high risk APL. RESULTS: Early death rates at 7 and 30 days were 7% and 13%, respectively, including 4 patients who died before any treatment could be administered. Overall survival at 3 years was 76.5% (95% confidence interval, 63.9-85.2) for the entire cohort, and 82.5% (95% confidence interval, 69.7-90.2) if patients who died within 7 days of diagnosis were excluded. For 13 patients (18.8%), there was a delay of 5 or more days from time of initial presentation at a peripheral hospital until arrival at the leukemia center and administration of all-trans retinoic acid; only 1 of these patients died within 30 days. CONCLUSION: Despite the challenges faced in the public healthcare system of a developing country, outcomes of APL patients treated at our center are similar to outcomes from developed countries.

Outcome and Prognostic Features in Pediatric Acute Megakaryoblastic Leukemia Without Down Syndrome: A Retrospective Study in China.

BACKGROUND: Acute megakaryoblastic leukemia (AMKL) is a biologically heterogeneous subtype of acute myeloid leukemia that originates from megakaryocytes. Patients with AMKL with non-Down syndrome (DS) had a poorer prognosis. However, clear prognostic indicators and treatment recommendations for this subgroup remain controversial. PATIENTS AND METHODS: Herein, we performed a retrospective study on 40 patients (age ≤ 18 years) with non-Down syndrome AMKL at our institution. We assessed the effect of different prognostic factors, such as their cytogenetic abnormalities, early treatment response, and the role of hematopoietic stem cell transplantation (HSCT) as post-remission treatment on the outcomes. RESULTS: The complete remission (CR) rate of the patients was 57.9% and 81.1%, respectively, at the end of induction therapy 1 and 2. The overall survival (OS) and event-free survival rates at 2 years were 41% ± 13% and 41% ± 10%, respectively. An analysis of the cytogenetic features showed that patients with +21 or hyperdiploid (> 50 chromosomes) had significantly better OS than those in other cytogenetic subgroups (Plog-rank = .048 and Plog-rank = .040, respectively). Besides cytogenetics, an excellent early treatment response (CR and minimal residual disease < 1% after induction therapy 1) also provided a significant survival benefit in univariate analysis in our study. However, multivariate analysis indicated that allogeneic HSCT was the only independent prognostic marker (relative risk, 11.192; 95% confidence interval, 2.045-61.241; P = .005 for OS and relative risk, 5.400; 95% confidence interval, 1.635-17.832; P = .006 for event-free survival, respectively). CONCLUSION: AMKL in patients with non-Down syndrome has a poor outcome. With poor OS but CR rates comparable with other acute myeloid leukemia subtypes, allogenic HSCT may be a better option for post-remission therapy than conventional chemotherapy, especially for those having a poor response to induction therapy.

Prognostic Factors in Childhood Acute Myeloid Leukemia; Experience from A Developing Country.

BACKGROUND: In the developed world, 5-years survival of childhood acute myeloid leukaemia (AML) has improved to 70%. However, the survival rates in the developing world are below 40%. The main contributing factors to these reduced survival rates are a late presentation, malnutrition and high treatment-related mortality. AIM: To document the factors affecting treatment outcome of childhood AML at a tertiary care facility of Pakistan. METHODS AND RESULTS: All newly registered cases of AML under 18 years of age from January 1, 2012 onwards who completed their treatment before November 30, 2019 were included. Data of 219 cases of AML containing 140 (63.9%) males and 79 (36.1%) females was analyzed. The mean age was 6.30 ± 3.66 years. Pallor was the commonest presenting features in 180 (82.2%) and M2 was the commonest French American-British (FAB) subtype in 103 (47.0%) cases. In univariate analysis, high white blood cells (WBC) count at presentation (P = .006), poor nutritional status (P = .005), unfavourable cytogenetics (P = .019), certain types of FAB AML subtype (P = .005), and use of etoposide in induction chemotherapy (P = .042) significantly adversely affected overall survival (OS). Neutropenic sepsis and bleeding were the major causes of treatment-related mortality. Response to induction chemotherapy was the most significant prognostic factor in the multivariate analysis (P = <.001). After a median follow-up of 40.96 ± 26.23 months, 5-year OS and DFS of the cohort were 40.6% and 38.3% respectively. CONCLUSIONS: In this largest cohort of childhood AML from Pakistan, high WBC count at presentation, malnutrition, unfavourable cytogenetics and use of etoposide during induction chemotherapy were associated with decreased OS and DFS rates. Response to the induction chemotherapy was the most significant prognostic factor.

Effects of post-remission chemotherapy before allo-HSCT for acute myeloid leukemia during first complete remission: a meta-analysis.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is most frequently used to treat acute myeloid leukemia (AML). Whether patients should routinely receive consolidation chemotherapy before proceeding to transplant after achieving first complete remission (CR1) has been a subject of debate. We performed a systematic review and meta-analysis of studies examining the impact of post-remission chemotherapy before allo-HSCT in patients with AML in CR1. Six studies including 1659 patients were included in the meta-analysis. The pooled hazard ratio (HR) for overall survival was 0.9 (95% confidence interval [CI] 0.77-1.05, P = 0.182), and the pooled HR for leukemia-free survival was 0.87 (95% CI 0.75-1.0, P = 0.07). No survival advantage was observed for post-remission chemotherapy before reduced-intensity conditioning or myeloablative conditioning (MAC) allo-HSCT for AML in CR1. The pooled relative risk for relapse incidence (RI) was 1.02 (95% CI 0.82-1.28, P = 0.834). Post-remission chemotherapy before allo-HSCT did not significantly affect the RI in patients with AML in CR1. The analyses revealed no significant benefit of post-remission consolidation chemotherapy in patients who received allo-HSCT. We recommend proceeding to allo-HSCT as soon as CR1 is attained.

Multimodal Management of Locally Advanced Neuroendocrine Cervical Carcinoma: A Single Institution Experience.

OBJECTIVE: The aim of this study was to report our institutional experience of a multimodal approach for treatment of locally advanced high-grade neuroendocrine cervical cancer. METHODS AND MATERIALS: Patients with primary locally advanced neuroendocrine cervical cancer diagnosed between 2001 and 2014 were included. The scheduled treatment sequence was as follows: pelvic +/- para-aortic radiotherapy (according to tumor stage), associated with chemotherapy based on platine-derivate and etoposide regimen, followed with a brachytherapy boost, then completion surgery if there was no progression +/- consolidation etoposide chemotherapy (for a total of 5-6 cycles). Disease-free survival (DFS) and overall survival (OS) were reported and prognostic factors were searched. RESULTS: A total of 24 patients fulfilled inclusion criteria. Median age was 48 (range 22-77 years). Fourteen patients (58%) had pelvic lymph node metastases. After chemoradiation/brachytherapy, a radical hysterectomy could be performed in 18 of 24 patients (75%). Histologically complete resection was achieved in 14 (78%) of 18 patients. Complete pathological response was reported in 7 (39%) of 18. With median follow-up of 29.7 months, 10 (42%) of 24 patients experienced tumor relapse, all associated with distant failure, including one local failure. The DFS and OS rates estimated at 3 years were 55% and 63%, respectively. Lymph node metastases and tumor stage were prognostic for DFS (P = 0.016 and P = 0.022, respectively). Complete resection was associated with a lower incidence of relapses, as compared with microscopically incomplete resection (P = 0.04). A total of 12 (86%) of 14 patients with histologically complete resection were in complete remission at last follow-up. Apart from manageable acute hematological toxicities, most treatment complications were mild to moderate. CONCLUSIONS: This series based on a multimodal management compares favorably with previously published data. Most patients could be eligible to surgery, and complete remission was achieved in 85% of those amenable to complete resection.

History of consolidation is prognostic in acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplantation in minimal residual disease-negative first complete remission.

BACKGROUND: Prognostic factors among acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in minimal residual disease (MRD)-negative first complete remission (CR1) are unknown. We retrospectively attempted to answer the following question: In AML patients undergoing allo-HCT in MRD-negative CR1, does a history of prior consolidation provide additional prognostic information? METHODS: The inclusion criteria were: (i) Age > 18 years, (ii) AML in CR1 after 1-2 cycles of intensive induction chemotherapy, with or without consolidation, (iii) Allo-HCT between 1/2003 and 4/2016 at our institution, (iv) Available standard-sensitivity 4-color flow cytometry results from a bone marrow aspiration at diagnosis and after completion of all previous chemotherapy within one month prior to HCT, (v) Flow cytometry-based MRD-negative status at the time of HCT. RESULTS: A history of prior consolidation was associated with favorable overall survival (Hazard Ratio [95% Confidence Interval]: 0.59 [0.35-0.99], P = .046), relapse-free survival (0.60 [0.37-0.96], P = .036), and relapse (0.50 [0.27-0.92], P = .025). Analysis of potential sources of bias was unrevealing. CONCLUSIONS: In AML patients undergoing allo-HCT in MRD-negative CR1, a history of prior consolidation was associated with favorable outcomes. If the path to pre-HCT MRD negativity includes consolidation, it may identify patients with improved prognosis following HCT in MRD-negative state. These results warrant validation in larger cohorts.

Acute respiratory infections in children and adolescents with acute lymphoblastic leukemia.

BACKGROUND: Knowledge regarding the incidence, clinical course, and impact of respiratory viral infections in children with acute lymphoblastic leukemia (ALL) is limited. METHODS: A retrospective cohort of patients with newly diagnosed ALL who were treated on the Total Therapy XVI protocol at St Jude Children's Research Hospital between 2007 and 2011 was evaluated. RESULTS: Of 223 children, 95 (43%) developed 133 episodes of viral acute respiratory illness (ARI) (incidence, 1.1 per 1000 patient-days). ARI without viral etiology was identified in 65 patients (29%) and no ARI was detected in 63 patients (28%). There were no significant associations noted between race, sex, age, or ALL risk group and the development of ARI. Children receiving induction chemotherapy were found to be at the highest risk of viral ARI (incidence, 2.3 per 1000 patient-days). Influenza virus was the most common virus (38%) followed by respiratory syncytial virus (33%). Of 133 episodes of viral ARI, 61% of patients were hospitalized, 26% experienced a complicated course, 80% had their chemotherapy delayed, and 0.7% of patients died. Twenty-four patients (18%) developed viral lower respiratory tract infections (LRTI), 5 of whom (21%) had complications. Patients with viral LRTI had a significantly lower nadir absolute lymphocyte count; were sicker at the time of presentation; and were more likely to have respiratory syncytial virus, to be hospitalized, and to have their chemotherapy delayed for longer compared with those with viral upper respiratory tract infections. CONCLUSIONS: Despite the low incidence of viral ARI in children with ALL, the associated morbidity, mortality, and delay in chemotherapy remain clinically significant. Viral LRTI was especially associated with high morbidity requiring intensive care-level support. Cancer 2016;122:798-805. © 2015 American Cancer Society.