Obesity in Children with Acute Promyelocytic Leukemia: What is its Incidence and Prognostic Significance?

Objective: To compare outcomes data of obese and non-obese pediatric patients with acute promyelocytic leukemia from the Cancer and Leukemia Group B trial C9710 and the Children’s Oncology Group trial AAML0631. Methods: Data including demographics, adverse events, overall survival and event free survival was analyzed, with a focus on mortality in obese patients. Results: The incidence of obesity was 34% on C9710 and 35% on AAML0631. There was significantly lower overall survival in the obese population on AAML0631. Thirteen patients died during therapy or in follow up; seven of these occurred during induction. Conclusion: The incidence of obesity is higher in patients with APL compared to the general population. The presence and degree of obesity can influence OS on the most current treatment regimen. This implies the need for close management of obese patients at diagnosis as well as reinforces the need for further research on obesity driven APL

Fetal Hemoglobin, Serum Total Cholesterol, Plasma Phosphate and Serum Calcium Levels in Patients with Leukemia and Lymphoma

In this study, fetal hemoglobin (HbF), blood total cholesterol, phosphate and calcium levels of leukemia and lymphoma cases in Mandalay were determined. It was a cross-sectional, comparative study. Thirty adult cases of leukemia and lymphoma and equal number of control subjects of comparable age (14 to 80 yrs) and sex were studied. Mean HbF of leukemia group (n=9), acute myeloid leukemia (AML) subgroup (n=6) and controls (n=30) were 2.72±0.47%, 3.17±0.69% and 1.39±0.25% of total Hb, respectively. The HbF levels of leukemia group and AML were significantly higher than that of controls (p<0.02). Mean serum total cholesterol levels of leukemia group, AML subgroup and controls were found to be 126.5±17.38 mg%, 137.96±24.66 mg% and 177.18±7.68 mg%, respectively. Cholesterol levels of leukemia group and AML were lower than that of controls. Mean plasma phosphate levels of leukemia and lymphoma cases (n=30), leukemia group (n=9) and lymphoma group (n=21) were 1.21±0.07 mmol/l, 1.33±0.17 mmol/l and 1.15±0.06 mmol/l, respectively. Mean phosphate level of controls was 0.94 mmol/l. Plasma phosphate levels of the whole cases and individual case groups were significantly higher than that of controls (p<0.001). Mean serum calcium levels of the whole cases, leukemia group and lymphoma group were 10.16±0.36 mg%, 10.03±0.75 mg% and 10.21±0.45 mg%, respectively. Mean serum calcium level of controls was 8.55±0.14 mg%. Serum calcium levels of the whole cases and individual case groups were found to be significantly higher than that of controls (p<0.01). The study showed that not only raised HbF but also hypocholesterolaemia might be the diagnostic clues in leukemia cases. Recognition of blood phosphate and calcium changes leads to appropriate therapy and a reduction of morbidity.

Low Serum Albumin Level Predicts the Risk of Azacitidine Early Discontinuation in MDS, CMML and 20-30% AML Patients- Results from the Polaza, the Retrospective Study of the Polish Adult Leukemia Group

Background: Azacitidine is the current standard of care for higher risk MDS patients (HR MDS) changing the natural course of diseases. Early drug discontinuation (receiving less than 4 azacitidine cycles - early failure - EF) is a poor prognostic marker, while factors affecting early failure are largely unknown. Objectives: To identify predictive factors for early azacitidine failure in MDS/CMML/low blast percentage AML patients Methods: The study included retrospectively MDS/CMML and 20-30% bone marrow blasts AML patients treated from 2008 to 2019 in 12 Polish hematologic centers cooperating within Polish Adult Leukemia Group (PALG). Baseline demographic, laboratory, clinical and treatment characteristics were obtained and were evaluated as potential EF predictors. Cox proportional hazard models were used to define statistical significance of variables using the R statistical platform. Results: We collected data on 315 patients with MDS (67%), CMML (12%) and with AML (21%). Median age was 69 years and 61% were male. Median number of azacitidine cycles was 7 (1-69) and 84 patients (29%) received maximum 3 cycles. Patients achieved more than 3 cycles showed better OS compared to those ≤ 3 cycles (20 months vs 4 months)(p<0.05)( Figure 1). In univariate analysis the following features were significantly predictive for early failure: poorer cytogenetics IPSS (OR 1.87, 95% CI 1.36-2.56; p<0.001), poorer cytogenetics IPSS R (OR 1.52, 95% CI 1.21-1.89; p< 0.001), poorer IPSS score (OR 1.77, 95% CI 1.18-2.66; p0.006), poorer ISS R score (OR 1.51, 95% CI 1.07-2.14; p=0.02), earlier treatment (OR 2.43, 95% CI 1.33-4.44; p=0.004), serum albumin level (OR 0.44, 95% CI 0.27-0.74; p=0.002), coexistence of autoimmune disease (OR 1.49, 95% CI 1.12-1.99; p=0.007), ECOG performance status (OR 1.49, 95% CI 1.12-1.99, p=0.007) and ativiral prophylaxis management (OR 0.40, 95% CI 0.19-0.87, p=0.020). In the multivariate analysis only serum albumin level retained its significance as independent factor affecting the risk of EF (OR 0.30, 95% CI 0.13-0.7; p=0.005). Decrease of albumin level by 1 g/dL rises the risk of EF occurence by 70%. Conclusions: Our analysis confirmed that patients with premature azacitidine treatment discontinuation ≤ 3 cycles have worse outcome. The pretreatment lower serum albumin level was identified as an independent predictor of early failure occurence. Figure 1. Overall survival in patients treated with ≤ 3 azacitidine cycles and > 3 cycles Disclosures Golos: Novartis: Honoraria. Basak:Celgene: Honoraria; Teva: Honoraria.

Analysis of Predictive Factors for Early Response to Ruxolitinib in 266 Patients with Myelofibrosis from the Polish Adult Leukemia Group (PALG) Registry

Background: Ruxolitinib (RUX), an inhibitor of JAK1/JAK2 kinases, is the only drug approved for the treatment of myelofibrosis (MF). The main clinical effects of RUX therapy include decrease of splenomegaly and reduction of burden of constitutional symptoms. Importantly, predictive factors influencing response and toxicity of RUX are largely unknown. Since 2017 therapy with RUX has been reimbursed in Poland for patients (pts) with MF, and large proportion of these pts has been followed for drug efficacy and tolerance within registry of the Polish Adult Leukemia Group (PALG). Objectives: The primary objective of the study was to identify baseline factors influencing probability of achievement of early response to RUX in MF. Patients and Methods: We retrospectively analyzed outcome of treatment with RUX after 6 months of therapy within the Polish Ministry of Health RUX reimbursement program in pts with primary MF (PMF) and MF secondary to polycythemia vera (post-PV MF) or essential thrombocythemia (post-ET MF). The inclusion criteria to the RUX reimbursement program were as follows: 1) diagnosis of MF confirmed by a recent bone marrow biopsy, 2) intermediate-2 or high risk IPSS, and 3) presence of splenomegaly and constitutional symptoms. Response to RUX was objectively categorized in regard to splenomegaly and MF symptoms. "Spleen Response" was defined as ≥ 50% reduction of the difference between baseline maximal length of spleen and upper limit of normal (120mm) measured by ultrasonography while "Symptoms Response" was defined as ≥50% reduction of the MF constitutional symptoms as assessed by MPN-SAF TSS score. Influence of potential prognostic factors (age, sex, time from MF diagnosis to RUX treatment, PMF vs post-ET MF and post-PV MF, leukocytosis, number of platelets, hemoglobin level, IPSS, DIPSS, grade of fibrosis in bone marrow, genetic status of MF) on probability of response was tested by univariate and multivariate logistic regression. Results: We enrolled 266 MF pts (56.8% PMF, 26.7% post-PV MF, 16.5% post-ET MF) undergoing treatment with RUX in 14 Polish hematology centers. Pts' median age was 67 years (range 21-86), while 59% of the group were females. Thirty-two% of pts were classified as high risk, 56% as intermediate-2 risk and 12% as intermediate-1 risk according to DIPSS score. JAK V617F mutation was found in 83%, CALR in 12%, MPL in 1.5%, and 3.5% of pts were triple negative. The median time from diagnosis of MF to start of RUX therapy was 30 months (range 0-321). At RUX therapy initiation median spleen length was 210 mm (range 100-300), and median symptoms score was 41 (range 4-93). During first six months the therapy has been continued in all but 26 (9.8%) pts in whom the treatment was withdrawn mainly because of lack of effectiveness. The most common hematologic adverse events included anemia (grade ≥3 in 27% of pts) and thrombocytopenia (grade ≥3 in 8% of pts). Major thrombotic events occurred in 3 pts. Among infectious complication 11 upper respiratory tract infections, 4 urinary tract infections, 3 herpes zoster infections, 3 pneumonias of unknown etiology and 1 case of tuberculosis were reported. Regarding the established categories of response to RUX, at 6th month of therapy "Spleen Response" was detected in 50% of patients. The only pre-treatment factor significantly associated with the probability of achievement of "Spleen Response" by multivariable analysis was leukocytosis ≥25 G/L (OR 3.57, 95%CI 1.40-9.06, p=.007). In contrast "Symptoms Response" after 6 months of RUX therapy was found in larger proportion of patients accounting for 77% of the studied population. Multivariable analysis revealed that time-interval between MF diagnosis and RUX start (p=.028) and platelets >200 G/L (OR 2.09, 95%CI 1.16-3.77, p=.014) remained significant predictors of "Symptoms Response". Conclusions: In this study we found that in real life setting efficacy of RUX is more promising, especially in terms of symptoms reduction, and better tolerated, as compared to the results of randomized COMFORT studies. Furthermore, our analysis revealed that simple laboratory parameters such as leukocytosis and platelets number may constitute useful predictors of early response to RUX therapy. Finally, since shorter time interval between MF diagnosis and RUX therapy correlated with better "Symptoms Response", introducing RUX earlier during the course of the disease may be more beneficial for pts. Disclosures Gora Tybor: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Golos:Novartis: Honoraria. Sacha:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lewandowski:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Niesiobedzka-Krezel:Novartis: Honoraria. Bieniaszewska:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Grzybowska-Izydorczyk:Novartis: Honoraria. Seferynska:Novartis: Honoraria. Patkowska:Novartis: Honoraria. Świstek:Novartis: Honoraria. Jamroziak:Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding.