Carbapenem-Resistant Enterobacteriaceae (CRE) among Children with Cancer: Predictors of Mortality and Treatment Outcome.

Carbapenem-resistant Enterobacteriaceae (CRE) is an important emerging threat among pediatric cancer patients, with a high mortality rate. This retrospective study included all pediatric cancer patients with (CRE) bloodstream infections (BSIs) at a children's cancer hospital in Egypt (2013-2017). Two hundred and fifty-four pediatric cancer patients with CRE BSI were identified; 74% had hematological malignancies, and 26% had solid tumors. Acute myeloid leukemia was the most common hematological malignancy (50%). The main clinical features for acquiring CRE-BSI were previous antibiotics exposure (90%), profound neutropenia (84%), prolonged steroid use (45%), previous colonization with a resistant pathogen (35%), ICU admission within 90 days (28%), and central venous catheter use (24%). E. coli was the most common isolated pathogen (56%), followed by Klebsiella pneumoniae (37%). All isolates were resistant to carbapenem with an MIC < 4-8 µg/mL in 100 (45%) and >8 µg/mL in 153 (55%). The overall mortality rate was 57%, and 30 day mortality was reported in 30%. Upon multivariate analysis, for the patients with Klebsiella pneumoniae BSI, carbapenem resistance with an MIC > 8 µg/mL and associated typhlitis or pneumonia were predictors of poor outcome. In conclusion, CRE-BSI is a major threat among pediatric cancer patients in limited resource countries with limited options for treatment. Antimicrobial stewardship for early detection through routine screening, adequate empirical treatment, and timely adequate therapy may impact the outcome for such high-risk patient groups.

Effects of COVID-19 on Pediatric Cancer Care: A Multicenter Study of 11 Middle Eastern Countries.

During the COVID-19 pandemic, major challenges are facing pediatric cancer centers regarding access to cancer centers, continuity of the anti-cancer therapy, hospital admission, and infection protection precautions. Pediatric oncologists actively treating children with cancer from 29 cancer centers at 11 countries were asked to answer a survey from May 2020 to August 2020 either directly or through the internet. COVID-19 pandemic affected the access to pediatric cancer care in the form of difficulty in reaching the center in 22 (75.9%) centers and affection of patients' flow in 21 (72.4%) centers. Health care professionals (HCP) were infected with COVID-19 in 20 (69%) surveyed centers. Eighteen centers (62%) modified the treatment guidelines. Care of follow-up patients was provided in-hospital in 8(27.6%) centers, through telemedicine in 10 (34.5%) centers, and just delayed in 11 (38%) centers. Pediatric oncologists had different expectations about the future effects of COVID-19 on pediatric cancer care. Seventy-six percent of pediatric oncologists think the COVID-19 pandemic will increase the use of telemedicine. Fifty-five percent of pediatric oncologists think if the COVID-19 pandemic persists, we will need to change chemotherapy protocols to less myelosuppressive ones. Collaborative studies are required to prioritize pediatric cancer management during COVID-19 era.

COVID-19-Associated Pulmonary Fungal Infection among Pediatric Cancer Patients, a Single Center Experience.

Patients with COVID-19 are at risk of developing secondary complications such as invasive pulmonary aspergillosis and mucormycosis. This is a retrospective study including all cancer children diagnosed with COVID-19-associated pulmonary fungal infection (CAPFI) during the period 2020-2021. A total of 200 patients were diagnosed with COVID-19, out of which 21 (10%) patients were diagnosed with CAPFI, 19 patients (90%) with COVID-aspergillosis (CAPA), and 2 (10%) patients with COVID-mucormycosis (CAM). Patients with CAPFI were classified using the "2020 ECMM/ISHAM consensus criteria"; proven in 2 (10%) patients, probable in 12 (57%), and possible in 7 (33%) patients. Although the hematological malignancy patients were already on antifungal prophylaxis, breakthrough fungal infection was reported in 16/21 (75%), 14 (65%) patients had CAPA while on echinocandin prophylaxis, while 2 (10%) patients had CAM while on voriconazole prophylaxis. Overall mortality was reported in 8 patients (38%) while CAPFI-attributable mortality was reported in 4 patients (20%). In conclusion, clinicians caring for pediatric cancer patients with COVID-19 should consider invasive pulmonary fungal infection, even if they are on antifungal prophylaxis, especially with worsening of the clinical chest condition. A better understanding of risk factors for adverse outcomes may improve clinical management in these patients.

Clinical characteristics and outcome of invasive fungal sinusitis in children with hematological malignancies.

Invasive fungal sinusitis (IFS) is a rare disease that requires careful attention and prompts management due to its high mortality among pediatric patients with hematological malignancies. This is a retrospective analysis of pediatric patients with hematological malignancies treated at Children's Cancer Hospital Egypt 57 357 (CCHE) through the period from 2008 till 2016 with proven IFS. Thirty-four patients were diagnosed with IFS. Five (15%) patients had an invasive rhino-cerebral fungal disease. Mucorales were isolated in 50% (n = 17) patients, Aspergillus in 38% (n = 13) patients, and mixed fungal in 12% (n = 4) patients. Sinuses were the only localized site in (45%). Extra-nasal spread was reported in 20 patients; Sino-pulmonary in 35% (n = 12), sino-cerebral in 15% (n = 5), and sino-orbital in 5% (n = 2) patients. Combined antifungal therapy with surgical debridement was done in 59% of patients with a better outcome when compared to those who received only medical antifungal treatment (P = .01). The overall mortality rate at week 12 was 35% (n = 12), and IFS attributable mortality was 20% (n = 7). IFS with cerebral extension carried the highest mortality rate for both 12-week all-cause (P = .04) and fungal-attributable (P = .01) mortality. Pediatric patients with hematologic malignancies are susceptible to invasive fungal sinusitis (IFS). Surgical debridement, combined with antifungal therapy, improves outcomes among those patients. IFS patients with cerebral extension had a higher risk of mortality. LAY SUMMARY: We studied the characteristics of invasive fungal sinusitis in children with hematological malignancies. Mucormycosis was the most common cause. Surgical debridement, combined with anti-fungal therapy, improves outcomes. Patients with rhino-cerebral fungal disease had a higher risk of mortality.

Role of matrix metalloproteinase MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP-1) in the clinical progression of pediatric acute lymphoblastic leukemia.

BACKGROUND: Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed. METHODS: The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38- cancer stem cells (CSCs) were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis. RESULTS: There was a significant increase in TIMP-1 [1.52 (0.41-10) versus 0.91(0.6-1.12); respectively, p < 0.001], and CSCs CD34+CD38- [1 (0.03-18.6) versus 0.3 (0.01-1.1), p < 0.001] expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, area under curve (AUC) of MMP-2 were (80.3%, 53.3% and 0.568, p = 0.404), and of MMP-9 were (53.9%, 40% and 0.660, p = 0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, p < 0.001), and that of CD34+CD38- CSCs were (78.9%, 73.3% and 0.855, p < 0.001). Increased TIMP-1 expression associated with the high-risk disease (p < 0.001). CD34+CD38- CSCs and MMP-2 overexpression associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 (p < 0.05). TIMP-1 overexpression is associated with shorter DFS and OS rates (p = 0.009 and p = 0.048). Multivariate logistic regression analysis showed that both TIMP-1 [OR: 4.224, p = 0.046], and CD34+CD38- CSCs [OR: 6.873, p = 0.005] could be potential independent diagnostic factors for pediatric ALL. CONCLUSION: TIMP-1 and CD34+CD38- CSCs could be possible useful diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.

Characterization of CRLF2 Expression in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a heterogeneous disease with several underlying genetic ab-normalities. Several studies have tried to elucidate the prognostic significance of cytokine receptor-like factor 2 (CRLF2) overexpression in pediatric B-cell precursor (BCP)-ALL; however, it is still controversial. METHODS: CRLF2 expression was assessed by flow cytometry in 87 newly diagnosed BCP-ALL pediatric patients, and 80 age and gender-matched control group. Janus Kinase2 (JAK2) (R683) mutation analysis was also performed in those identified to have CRLF2 overexpression with adequate DNA samples by direct sequencing. RESULTS: CRLF2 overexpression was identified in 26/87 (29.9%) of our patients with cutoff set at mean fluorescence intensity (MFI = 3.8) using the Receiver Operating Characteristic (ROC) curve. There were no significant differences in the clinical and laboratory features between patients with high and low-CRLF2 expression, apart from thrombocytopenia which showed statistically significant association with the low-expression group (p = 0.041). Sequence analysis of samples with high CRLF2 expression (n = 23) revealed that 2/23 (8.7%) cases harbored the mutation JAK2 (R683). CRLF2 levels did not have a significant impact on either overall survival (OS) or disease free survival (DFS) (p = 0.601; p = 0.212, respectively). CONCLUSIONS: CRLF2 overexpression was not an adverse parameter in pediatric BCP-ALL patients. However, patients with CRLF2 overexpression may harbor the JAK2 mutation presenting a group that can benefit from targeted therapy by kinase inhibitors. The usage of CRLF2 expression to monitor minimal residual disease of BCP-ALL would be an area of interest for further evaluation.

Duplication 1q is highly correlated with poor prognosis in high hyperdiploid pediatric B-acute lymphoblastic leukemia.

BACKGROUND: The role of structural abnormalities in high hyperdiploidy (HeH) has been debatable, with few studies that addressed recurrent translocations with concurrent HeH (t-HeH). We aimed at the characterization of HeH cases in pediatric B-acute lymphoblastic leukemia (B-ALL) patients with special emphasis on the structural abnormalities including t-HeH. PATIENTS AND METHODS: Our study included all patients diagnosed with HeH over the period from January 2016 to April 2019 presenting to the Pediatric Oncology Department, National Cancer Institute, Cairo University. RESULTS: Among 480 de novo B-ALL pediatric patients, HeH was detected in eighty (16.7%) cases with a median age of 5 years. t-HeH was identified in 17/480 (3.5%) cases: 9(1.9%) with t(12;21), 7(1.5%) with t(9;22), and 1(0.2%) with t(4;11). Duplication (1q) was the most prevalent structural abnormality in c-HeH (hyperdiploidy without recurrent translocations) (n = 12,15%). Children ≥10 years or presenting with white blood cells (WBC) ≥50 × 109 /L) had an inferior 3 year-overall survival as compared to younger children (P = .003), and to lower WBC (P = .02). Duplication (1q) was an independent adverse parameter on the disease-free survival (DFS) of c-HeH patients (P = .004). CONCLUSIONS: Older age and WBC ≥ 50 × 109 /L were adverse prognostic factors. Duplication (1q) is correlated with lower DFS in c-HeH patients. t-HeH has distinct patterns of chromosomal gain.

Acute lymphoblastic leukemia-like treatment regimen provides better response in mixed phenotype acute leukemia: a comparative study between adults and pediatric MPAL patients.

Mixed phenotype acute leukemia (MPAL) is a rare type of leukemia with a limited number of studies conducted to characterize its clinical spectrum and most importantly the best treatment modality. MPAL blasts show more than one phenotype either myeloid/monocytic with T- or B-lymphoid or extremely rare triple lineage associated phenotypic markers. This study aimed to characterize MPAL cases with special emphasis on comparing adult and pediatric age groups, exploring treatment regimens, and clinical outcome. Among 2571 acute leukemia patients, 102 MPAL cases fulfilling the 2008/2016 WHO diagnostic criteria of MPAL were recruited in the study. The incidence of MPAL was 4% of acute leukemia patients. Pediatric cases were 54 (53%) while adults were 48/102 (47%). Myeloid/B-lymphoid phenotype was found in 86/102 (84%), with BCR-ABL fusion gene transcript detected in 14/102(13.7%) patients. ALL-like treatment showed better response rates as compared with the myeloid based regimen (p = 0.001). MPAL behaves in a manner that resembles in clinical features, their lymphoid progenitor counterpart leukemias both in adults and pediatric patients with superior treatment response to ALL-like regimen, especially in adults.

Overexpression of CD200 and CD123 is a major influential factor in the clinical course of pediatric acute myeloid leukemia.

Acute myeloid leukemia (AML) accounts for approximately 20% of all pediatric acute leukemias. The outcome of AML is still unsatisfactory. CD123 and CD200 were demonstrated to play important roles in hematological malignancies. The aim of this study was to investigate the impact of CD200 and CD123 overexpression and the influence of both proteins on the clinical presentation and disease outcome. Bone marrow (BM) samples from 89 pediatric AML patients were obtained at presentation and after therapy. Cells from the bulk population and from the leukemia stem cell (LSC) compartment were examined by multi parametric flow cytometry. In the bulk population, CD200 was positive in 64/89 (71.9) samples, CD123 was positive in 62/89 (69.7%) samples, and dual CD200 and CD123 positivity was observed in 54/89 (60.7%) samples. CD200/CD123 expressions were observed in LSCs in 64/60 samples respectively (71.9%/67.4%), and co-expressed in 51 samples (57.3%). CD200 was overexpressed in secondary AML (p < 0.05). A multivariate analysis revealed that minimal residual disease (MRD) and lymphadenopathy were associated with CD200 overexpression. Moreover, lymphadenopathy, low platelet count, and MRD were independently associated with CD123 expression. The co-expression of CD200 and CD123 demonstrated a statistically significant relationship with unfavorable cytogenetic karyotypes and high total leucocyte count (TLC). The expression of CD200 and CD123 alone and together had an adverse impact on complete remission (CR), MRD positivity, and overall survival (OS). Cases with MRD on day 28 after induction displayed stable expression patterns of CD200 and CD123. CD200 and CD123 both had a negative influence on clinical presentation and treatment outcome, which remarkably worsened when both were concomitantly overexpressed. CD200 and CD123 can therefore be used as markers of MRD in AML and may also serve as therapeutic targets.

Relapsed Wilms' tumor in pediatric patients: challenges in low- to middle-income countries-a single-center experience.

BACKGROUND: Wilms' tumor (WT) affects one in 10,000 children and accounts for 5% of all childhood cancers. Although the overall relapse rate for children with WT has decreased to less than 15 %, the overall survival for patients with recurrent disease remains poor at approximately 50 %. The aim of the study to evaluate the outcome of relapsed Wilms' tumor pediatric patients treated at the National Cancer Institute (NCI), Egypt, between January 2008 and December 2015. RESULTS: One hundred thirty (130) patients diagnosed with WT during the study period, thirty (23%) patients had relapsed. The median follow up period was 22.3 months (range 3.6-140 months). The Overall Survival (OS) was 30.9% while the event-free survival (EFS) was 29.8% at a 5-year follow up period. Median time from diagnosis to relapse was 14.4 months. A second complete remission was attained in 18/30 patients (60%). The outcome of the 30 patients; 11 are alive and 19 had died. Three factors in our univariate analysis were prognostically significant for survival after relapse. The first was radiotherapy given after relapse (p = 0.012). The 5-year EFS and OS for the group that received radiotherapy were 41.9% versus 16.7% and 11.1% respectively for those that did not. The second was the state of lymph nodes among patients with local stage III (p = 0.004). Lastly, when risk stratification has been applied retrospectively on our study group, it proved to be statistically significant (p = 0.029). CONCLUSION: Among relapsed pediatric WT, radiotherapy improved survival at the time of relapse and local stage III with positive lymph nodes had the worst survival among other stage III patients.

Prognostic Significance of bcr-1 and bcr-3 Isoforms of PML-RARA and FLT3-ITD in Patients With Acute Promyelocytic Leukemia.

BACKGROUND: Acute promyelocytic leukemia (APL) has a characteristic peculiar morphologic and genetic features as well as a more favorable outcome. We studied the differential effect of bcr-1 and bcr-3 isoforms of the promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA) transcript together with FLT3 internal tandem duplication (FLT3-ITD) mutation status on the outcome of newly diagnosed de novo APL patients. PATIENTS AND METHODS: This cohort study included all patients diagnosed with APL at outpatient medical and pediatric oncology clinics of the National Cancer Institute, Cairo University, Cairo, Egypt, from May 2012 to January 2018. RESULTS: The study included 118 patients with APL, 71 adults (60.2%) and 47 children (39.8%). Median (range) age was 25 (1.5-70) years. Children had significantly higher total leukocyte count (≥10 × 109/L), disseminated intravascular coagulation (DIC), and thrombocytopenia (< 40 × 109/L) than adults (P = .04, .03, and .04, respectively), while the latter group had significantly higher hemorrhage than children (P = .04). FLT3-ITD mutation was detected in the whole group, children, and adults in 23.7%, 30.6%, and 24.6%, respectively. FLT3-ITD mutation was significantly associated with leukocytosis in the whole group (P = .039). bcr-3 was significantly associated with FLT3-ITD mutation in the whole APL cohort and in adults (P = .011, P = .022). All children (both bcr-1 and bcr-3) and all adult patients with bcr-3 experienced CR, while 22 (78.5%) of 28 patients with bcr-1 experienced CR (P = .04). APL patients with DIC and hemorrhage had significantly lower overall survival (P = .002 and < .001, respectively). Overall survival for APL in children was significantly better than in adults (P = .005). Multivariate analysis indicated that age was an independent prognostic variable affecting survival (hazard ratio = 2.6; 95% confidence interval, 1.3-5.3; P = .007) (adults had hazard ratio of death 2.6 times higher than children). DIC and FLT3-ITD were independent prognostic variables affecting survival in children with APL (hazard ratio = 12.3; 95% confidence interval, 1.46-104.61; P = .021; and hazard ratio = 5.2; 95% confidence interval, 1.01-26.95; P = .048, respectively). CONCLUSION: Age is an independent prognostic factor for APL. bcr-3 is significantly associated with FLT3-ITD in adults with APL. DIC and FLT3-ITD are adverse prognostic factors in children with APL. Despite children being at higher risk, outcome is better than in adults.

Clinical features and outcome of hepatosplenic fungal infections in children with haematological malignancies.

Hepatosplenic fungal infection (HSFI) is a severe invasive fungal infection observed during neutrophil recovery in patients with acute leukaemia treated with intensive chemotherapy. Retrospective analysis including all paediatric haematological malignancies patients with HSC treated in Children Cancer Hospital Egypt (2013-2018). Twenty-five patients with acute leukaemia developed HSFI (19 patients diagnosed as hepatosplenic candidiasis). Most of the cases (92%) occurred during the induction phase. Organs affected were as follows: liver in 18 patients, renal in 13 patients, spleen in 12 patients, skin in four patients and retina in one patient. Five (20%) patients had proven HSC, 14 (56%) probable and six (24%) possible HSFI. Ten patients had a PET-CT for response assessment. Candida tropicalis was the most common isolated spp. from blood/tissue culture. Six (24%) patients developed HSFI on top of antifungal prophylaxis. Steroids were given in 12 (52%) patients with HSFI as immune reconstitution syndrome (IRS). Caspofungin was the first line of treatment in 14 (56%) patients, liposomal amphotericin B in six (24%) patients and azoles in five (20%) patients. HSFI was associated with delayed of intensification phase of chemotherapy (median 42 days). The success rate was reported in 24 patients with complete response (68%) and partial response in (28%) patients, while failure (death) seen in 1(4%) patient. HSC is still a major challenge in paediatric leukaemias patients with impact on treatment delay and survival outcome. PET scan, non-culture diagnostics and steroid role evidence in IRS are growing. Antifungal stewardship for screening, early detection for high-risk patients and better response assessment is challenging.

Incidence, risk factors, and outcome of blood stream infections during the first 100 days post-pediatric allogeneic and autologous hematopoietic stem cell transplantations.

Bloodstream infections (BSI) are a frequently observed complication after hematopoietic stem cell transplant (HSCT). Retrospective analysis of clinical and microbiological data during the first 100 days from 302 consecutive pediatric patients who underwent HSCT for a malignant disease at our institute between January 2013 and June 2017. A total of 164 patients underwent autologous and 138 allogeneic HSCT. The overall incidence of BSI was 37% with 92% of infectious episodes occurring during the pre-engraftment phase. Gram-positive bacteria (GPB) accounted for 54.6% of the isolated pathogens, gram-negative bacteria (GNB) for 43.9%, and fungi for 1.4%. Coagulase-negative staphylococci and Escherichia coli were the most commonly isolated GPB and GNB, respectively. Forty-five percent of GNB were extended-spectrum beta-lactamase producers and 21% were multidrug-resistant organisms. Fluoroquinolone resistance was 92% and 68%, among GPB and GNB, respectively. Risk factors for BSI in univariate analysis were allogeneic HSCT, delayed time to engraftment more than 12 days, previous BSI before HSCT, and alternative donor. In multivariate analysis, only HSCT type (allogeneic vs autologous P = .03) and previous BSI within 6 months before HSCT (P = .016) were significant. Overall survival at day 100 was 98% and did not differ significantly between patients with and without BSI (P = .76). BSI is common in children undergoing HSCT for malignant diseases. Allogeneic HSCT recipients and previous BSI within 6 months before HSCT are associated with increased risk of post-transplant BSI. With current supportive measures, BSI does not seem to confer an increased risk for 100-day mortality.

Overview and outcome of mucormycosis among children with cancer: Report from the Children's Cancer Hospital Egypt.

Mucormycosis represents a real challenge in immunocompromised patients. This study aimed to describe the clinical characteristics, treatment outcome and infection-related mortality in our patients at the Children's Cancer Hospital 57357, Cairo, Egypt. This is a retrospective study during the period 2007-2017. Data analysis included demographic data, risk factors, diagnostic workup, treatment and outcome. During the study period, 45 patients developed proven mucormycosis according to EORTC/MSG criteria (2008). Ninety percentof cases were of haematological malignancies. Liposomal amphotericin B was the mainstay of treatment. Posaconazole was used as secondary prophylaxis in 35% of cases. Combination antifungal was used in three cases with progressive mucormycosis. Surgical intervention was achievable in 50% of cases. Therapy was successful in 35 patients (66%). Complications related to mucormycosis were seen in five cases with disfigurement and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in one case. Mucormycosis-related mortality was 33% (15 cases). Mucormycosis is a major cause of mortality among patients with haematological malignancies. Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, is the backbone of mucormycosis treatment.

Clinical Effect of Combined Mutations in DNMT3A, FLT3-ITD, and NPM1 Among Egyptian Acute Myeloid Leukemia Patients.

BACKGROUND: Genotypic mutation of fms like tyrosine kinase 3 (FLT3), Nucleophosmin (NPM1), and DNA-methyltransferase 3A (DNMT3A) has been involved in the leukemogenesis of acute myeloid leukemia (AML), with the well known poor prognostic role of FLT3 and DNMT3A and favorable role for the NPM1 mutation. PATIENTS AND METHODS: A total of 123 patients with AML treated at the National Cancer Institute, Cairo University were examined for mutations in DNMT3A, FLT3, and NPM1 using polymerase chain reaction (PCR) for detecting FLT3 internal tandem duplication (ITD) and allele-specific PCR to detect DNMT3A and NPM1A mutations. Two-way direct sequencing and Gene Mapper version 4.0 software (Fred Hutchinson Cancer Research Center) sequencing were used as confirmatory tests for DNMT3A and NPM1A mutations, respectively. RESULTS: DNMT3A, FLT3-ITD, and NPM1A gene mutations were detected in 22 (17.9%), 22 (17.9%), and 24 (19.5%) patients, respectively. DNMT3A/FLT3, NPM1A/FLT3, and DNMT3A/NPM1A combined mutant genotypes were detected in 5 (4.1%), 9 (7.3%), and 3 (2.4%) patients, respectively. Two patients (1.6%) had triple mutant genotypes (DNMT3A/FLT3/NPM1A). FLT3 and DNMT3A mutations had a significant negative effect on complete response (CR) rates (P = .016). FLT3-ITD mutation was significantly associated with older age (P = .029), and lower overall survival (OS) rates (P = .046). DNMT3A/FLT3 combined mutant genotypes were significantly associated with a lower OS rate (P = .016). Mutant NPM1/wild type FLT3, wild type DNMT3A/FLT3, and mutant NPM1A/wild type DNMT3A combinations were significantly associated with higher CR rates (P = .006, P = .006, and P = .023, respectively). CONCLUSION: DNMT3A, FLT3-ITD, and NPM1A are frequent mutations in Egyptian AML. FLT3-ITD mutations are frequent in older patients. DNMT3A and FLT3-ITD mutations were associated with an unfavorable prognosis, but the NPM1A mutation has tendency to indicate a good prognosis.