Background:Core binding factor acute myeloid leukemia (CBF AML) encodes two recurrent cytogentic abnormalities, t(8;21) and inv (16) and carries an overall good prognosis, yet some cases relapse. Aims:is to define unfavorable group of CBF AML by analysis of (C‐KIT and FLT3‐ITD) and to correlate with outcome of therapy.Methods:Prospective study started at Jan 2015 till June 2017, and included 70 patients CBF AML diagnosed and managed at medical oncology department of National Cancer Institute (NCI), Cairo University. All patients received standard of care protocol at NCI (“3+7”induction followed by 3‐4 courses of high dose cytarabine consolidation. The study was approved by the Institutional Review Board (IRB), of NCI, Egypt.Results:the median age was 31 years (18‐60, with a male/female ratio of 4/3. 42(60%) patients had t(8;21) and 28 patients had inversion 16(40%). C‐KIT mutations (exon 8 and exon 17) were detected in 10/52 tested patients and FLT3‐ITD was detected in 3/70 patients. While patients with Inv.16 had more lymphadenopathy and splenomegaly, median initial leucocytic count and exclusive gum hyperplasia, HCV‐Ab positivity (8/42) was exclusively present in patients with t(8;21). Clinically, lymphadenopathy, pallor and dyspnea were associated with worse overall survival (OS)(<0.05). BM cellularity at day 28 of induction had a significant impact on survival (P = 0.002). Median OS was 19.5 month while median disease free survival (DFS) was not reached for the whole group. Patients with Inv.16 had non‐significant better DFS than patients with t(8;21)(P = 0.07). Neither C‐ KIT D816 V mutation nor FLT3‐ITD mutation had significant impact on OS or DFS, but when taken together (either C‐KIT or FLT3‐ITD mutant) had negative impact on DFS (P = 0.04).Summary/Conclusion:C‐KIT or FLT3‐ITD mutation had negative effect on DFS but not OS. HCV‐Ab positivity may be associated with t(8;21)AML, while Inv.16 is associated with more extramedullary diseaseimage
Background:In the era of novel anti‐myeloma agents and monoclonal antibodies (daratumumab) and due to their high cost, earlier low cost regimens (VAD or CyBorD) may be used.Aims:to compare outcome of treatment of CyBorD versus VAD regimens in multiple myelomaMethodsThis cohort study included 89 MM patients treated at National Cancer Institute (NCI), Cairo, Egypt from January 2011 to December 2015. All patients were evaluated clinically and laboratory for different responses with either lines of treatment (VAD versus CyBorD), and correlated with different survival parameters; progression free (PFS), disease free (DFS), and overall survival (OS), and clinico‐pathologic factors.Results:The median age of patients was 54 years (32‐76), with male predominance (male to female ratio 1.87:1). The most common presenting symptoms were bony pains (44.9%) followed by bony masses (22.5%), fractures (16.9%), pallor (7.9%), neurological symptoms (5.6%) and finally oliguria (2.2%). CyBorD have better overall response rate (≥PR) (p = 0.031), PFS (p = 0.004) and DFS (p= 0.013) as 1st line treatment compared to VAD regimen. Also in previously treated patients CyBorD showed better PFS (p = 0.039) compared to VAD regimen. There was a significant relation between age (p = 0.001& < 0.001) and ASCT (p= 0.001&0.034) with PFS and OS respectively.Summary/Conclusion:CyBorD have significant better overall response treatment (≥PR), PFS and DFS in 1st line treatment compared to VAD regimen. While in previously treated patients only PFS benefit for CyBorD over VAD regimen was obtained. Age and ASCT had significant effect on PFS and OSimage
7013 Background: Hairy cell leukemia (HCL) is rare B-cell lymphoproliferative disorder. Its treatment has evolved from splenectomy with time to failure (TTF) of 19 months to Cladribine that increased complete remission (CR) rate to 90%, with only small percentage of patients relapsing at 30 months. Cladribine (CDA) is originally administered intravenously as continuous infusion for 7 days; Subsequently, it was administered subcutaneously. This study aims at comparing efficacy and toxicity of Subcutaneous (SC) versus Intravenous (IV) administration of CDA in treatment of HCL. Methods: This retrospective study included HCL patients presented to National Cancer Institute and Nasser Institute, Cairo, Egypt, during period 2004-2010. Included patients received CDA as 1st or 2nd line with minimum follow up of 12 months. All files were reviewed for baseline clinical & laboratory parameters, route of administration, response, adverse events and survival. Results: This study included 49 eligible patients, 41 patients received CDA as 1st line treatment, while 8 patients as 2nd line. Eighteen patients were treated by continuous IV infusion whereas 31 patients by SC injections. Both groups were comparable regarding baseline clinical and laboratory parameters with no statistically significant difference. At median follow up period of 33.5 months, complete remission rate was 94% in IV group versus 97% in SC group (p=0.691); median TTF for IV group was 52.9 months while that for SC group was not reached (p=0.035). The median time to achieve CR in both arms was similar. By analyzing different factors affecting TTF using multivariate analysis, route of administration proved to be the only statistically significant factor (P=0.006). Regarding adverse events, there was no difference between both groups in hematological toxicities. IV route was associated with a significant higher incidence of mucositis (p=0.02) and viral infections (p=0.01). Hepatotoxicity and neurotoxicity were higher in SC group but difference was not statistically significant. Conclusions: SC administration of cladribine is an alternative route to IV in treatment of HCL with similar response rate, longer time to treatment failure and better tolerability.
Background:Acute promyelocytic leukemia (APL) has a characteristic peculiar morphologic, genetic features and more favorable outcome.Aims:is to study the differential effect of BCR‐1 and BCR‐3 isoforms of PML‐RARA together with FLT3‐ITD mutational status on outcome of APL patients.Methods:All patients referred to the outpatient medical and pediatric oncology clinic, National cancer institute (NCI), Cairo University, Egypt in the period from May 2012 to January 2018. The diagnosis of APL was based on morphologic examination of the bone marrow and peripheral blood smears and was confirmed by the detection of the PML‐RARA transcript by FISH and RT‐PCR.Results:the study included 118 patients with newly diagnosed de novo APL (71 (60%) adults and 47 (39.8%) children). Based on the initial TLC, pediatric APL patients have higher (48.9%) risk than adults (30%) (p = 0.044). The CR rate was 91% (77/84), after excluding early induction related deaths (18) and patients who did not receive treatment at NCI (no beds available) (16). All pediatric patients (both BCR‐1 and BCR‐3) and all adult patients with BCR‐3 achieved CR while 22/28 (78.5%) of patients with BCR‐1 achieved CR (p = 0.04). Adult patients with FLT3 mutation (5/8 = 62.5%) received more high‐risk regimen than patients with wild FLT3‐ITD (10/38 = 26.3%)(p = 0.047). FLT3‐ITD mutation was associated with more hemorrhage and DIC (p = 0.038), and lower 2‐year OS (96% v 44.6%)(p = 0.001) in pediatric patients. Also DIC and Hemorrhage are associated with lower 2‐year OS in pediatric patients (91.4% v 48.6%)(p < 0.001). The 1‐year and 2‐year OS for pediatric patients were better than adults (56.2% v 83% and 80.7 % v 49.8% respectively) with a median of 39.4 month versus 12month respectively (p = 0.005). On multivariate analysis, Age was an independent prognostic variable affecting survival, HR 2.6 (95% CI 1.3–5.3, P = 0.007)(adults had hazards ratio of death 2.6 times higher than pediatrics). DIC & FLT3‐ITD were independent prognostic variables affecting survival in the pediatric APL with HR 12.3 (95% CI 1.46–104.61, P = 0.021) and 5.2 (95% CI 1.01–26.95, P = 0.048) respectively.Summary/Conclusion:BCR‐1 isoform of PML‐RARA is associated with decreased response to ATRA‐based regimens in adult APL patients. DIC & FLT3‐ITD are adverse prognostic factors in pediatric APL patients. Age is an independent prognostic factor in APL patients (whole group). Despite higher high risk groups in pediatric patients, the outcome is better than adult patients.image
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