Hassan Alkhateeb

Vancomycin-resistant Enterococcus colonization and bloodstream infection: prevalence, risk factors, and the impact on early outcomes after allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia.

Screening for vancomycin‐resistant Enterococcus (VRE) is performed at many transplant centers, but data on the impact of VRE colonization and bloodstream infection (BSI) on hematopoietic cell transplantation (HCT) outcomes remain conflicting.

Monosomal Karyotype Predicts Adverse Prognosis in Patients Diagnosed With Chronic Myelomonocytic Leukemia: A Single-Institution Experience

INTRODUCTION Cytogenetic abnormalities have a significant prognostic effect in many hematologic neoplasms. Monosomal karyotype (MK), a newly recognized cytogenetic category, has been reported to be a marker of poor prognosis in patients with myelodysplastic syndromes and myelofibrosis, but its effect in chronic myelomonocytic leukemia (CMML) remains relatively unknown. PATIENTS AND METHODS A retrospective study of cases diagnosed with CMML found a total of 262 patients. Patient characteristics, cytogenetic data, and survival were analyzed. RESULTS Cytogenetic analysis found diploidy in 167 patients (64%). Trisomy 8 was the most frequent cytogenetic abnormality at 8% (22), followed by complex karyotype (CK) at 5% (14), (-)7 at 4% (10), and MK at 3% (7, of which 6 [86%] were also CK). Median overall survival was statistically significantly worse in MK-positive cases than in MK-negative cases (MK(+) vs. MK(-)). Patients with MK(+) only or CK(+)MK(+) did worse than any other group. CONCLUSION MK is a rare entity but can predict statistically significantly shorter overall survival among all other cytogenetic categories.

Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease

Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first-line treatment; however, less than one-half of patients achieve durable remission. Studies suggest that TNF-α, a cytokine released from the bone marrow during conditioning, is involved in the pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-TNF-α therapy with infliximab in 35 patients with steroid refractory (SR) aGVHD. Infliximab was administered intravenously at 10 mg/kg for a median of 4 doses (range, 1 to 6) on a weekly basis. The overall response rates were 40% (17% complete response [CR], 23% partial response [PR]) at 4 weeks, 23% (9% CR, 14% PR) at 8 weeks, and 17% (all CR) at 12 weeks. Twenty-nine (83%) patients had infectious complications within 12 weeks of initiation of infliximab. These infections included 40 bacterial infections, 6 invasive fungal infections, and 5 viral reactivations. Twelve patients (34%) died secondary to infections. Overall survival at 12 weeks and 6 months from the start of infliximab therapy was 37% (13 of 35) and 17% (6 of 35), respectively; with most deaths secondary to complications from GVHD and infections. In conclusion; the use of infliximab therapy in patients with SR-aGVHD is associated with a modest poorly sustained response along with a heightened risk of severe infections. Future studies with more effective and less toxic therapies are needed for these patients.

Prognostic interaction between bone marrow morphology and SF3B1 and ASXL1 mutations in myelodysplastic syndromes with ring sideroblasts

Prognostic interaction between bone marrow morphology and SF3B1 and ASXL1 mutations in myelodysplastic syndromes with ring sideroblasts Abhishek A. Mangaonkar, Terra L. Lasho, Christy M. Finke, Naseema Gangat, Aref Al-Kali , Michelle A. Elliott, Kebede H. Begna, Hassan Alkhateeb, Alexandra P. Wolanskyj-Spinner, Curtis A. Hanson, Rhett P. Ketterling, William J. Hogan , Animesh Pardanani, Mark R. Litzow, Ayalew Tefferi and Mrinal M. Patnaik 1

Corticosteroid use as adjunct therapy for respiratory syncytial virus infection in adult allogeneic stem cell transplant recipients

Respiratory syncytial virus (RSV) infection causes significant morbidity and mortality in allogeneic stem cell transplant (allo‐SCT) recipients. Although ribavirin and immunoglobulins are common components of therapy, the role of adjunct corticosteroids is not established.

Prognostic impact of combined NPM1+/FLT3− genotype in patients with acute myeloid leukemia with intermediate risk cytogenetics stratified by age and treatment modalities

The prognostic impact of combined NPM1+/FLT3- genotype is not well defined in elderly patients with acute myeloid leukemia (AML), and in the setting of different treatments, such as cytotoxic chemotherapy (Chemo), hematopoietic cell transplantation (HCT), or hypomethylating agents (HMA). Eighty-two elderly (age >60 years) and 78 younger adults (age 18-60 years) with newly diagnosed intermediate-risk cytogenetic AML were classified according to the presence or absence of NPM1+/FLT3- genotype, and treatments (Chemo vs. HCT. vs. HMA). The estimated 3-year overall survivals (OS) in elderly (N=17) and younger adults (N=13) with NPM1+/FLT3- treated with Chemo were 59% and 64%, respectively (P=0.71). In the absence of NPM1+/FLT3-, younger adults had a superior OS when treated with HCT than with Chemo (P<0.0001), but elderly showed no survival advantage with HCT after adjustment for baseline covariates. Elderly patients lacking NPM1+/FLT3- had a comparable OS when treated with Chemo vs. HMA (P=0.79). Combined NPM1+/FLT3- is associated with a favorable prognosis irrespective of age in AML patients treated with Chemo. In the absence of NPM1+/FLT3- genotype, younger adults undergoing HCT have an improved survival, while elderly have comparable OS when treated with Chemo vs. HMA.

Serum chromogranin-A-based prognosis in metastatic castration-resistant prostate cancer

Objective:To determine the prognostic value of serum chromogranin-A (CGA) in a two-cohort study of men with metastatic castrate resistant prostate cancer (mCRPC) and to compare with circulating tumor cells (CTCs)-based prognosis.Patients and methods:A two-cohort-based evaluation for serum CGA for prognostication in CRPC stage was performed using a screening cohort of 256 men with mCRPC and an independent validation cohort of 92 men with mCRPC. In both cohorts, men receiving proton pump inhibitors and those with non-castrate levels of testosterone (>50 ng/dl) were excluded. Serum CGA was measured in a homogeneous automated immunofluorescent assay using time-resolved amplified cryptate emission. In the validation cohort, CTC enumeration was also performed using the FDA-cleared CELLSEARCH® CTC test. Cox proportional hazard regression models were used for prognostic association of serum CGA and CTC counts with overall survival.Results:In the screening cohort, 200 men were eligible for analysis. The median serum CGA was 100.3 ng/mL (interquartile range: 67–161.3) and 34/200 were above the reference range. In the subset of men with Gleason scores ≥ 8, elevated CGA was associated with shorter overall survival [hazard ratio (HR) 2.19, p = 0.017]. In the validation cohort for 71 men eligible for analysis, the median serum CGA was 90 ng/mL (interquartile range: 55–156) and 31/71 patients had an elevated CGA. 51% of patients had a Gleason score ≥ 8 and 66/71 patients had CTCs enumerated with 26/66 with a CTC count ≥ 5 per 7.5 ml blood sample (unfavorable). Both elevated serum CGA (HR: 1.91, p = 0.043) and unfavorable CTC counts (HR: 2.97, p = 0.0012) were adversely associated with overall survival and patients with ≥ 5 CTCs and elevated serum CGA had the shortest overall survival (HR: 3.76, p = 0.008).Conclusion:Elevated serum CGA was negatively associated with OS in men with mCRPC. Serum CGA represents a prognostic biomarker that may complement CTC enumeration.

Hemolytic Uremic Syndrome Associated With Escherichia coli O157 Infection in an Allogenic Stem Cell Transplant Recipient

We report the development of a Shiga toxin–producing Escherichia coli O157 gastrointestinal infection associated with hemolytic uremic syndrome in an allogenic stem cell transplant recipient with a history of gastrointestinal graft-vs-host disease receiving long-term immunosuppression.

Elderly acute lymphoblastic leukemia: a Mayo Clinic study of 124 patients.

Abstract Poor outcomes in elderly acute lymphoblastic leukemia (ALL) are well recognized, but the contributors are ill-defined. We characterized 124 patients ≥60 years old at our institution. The majority (n = 102, 82%) were treated with intensive chemotherapy. Of these, 8/102 (8%) died within the first 100 days; 92/102 (90%) achieved complete remission (CR/CRi). Only 31/124 (25%) patients underwent allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) for the entire cohort was 19.8 months. In a multivariate analysis, ECOG performance status ≥2, high white blood cell count, and high lactate dehydrogenase (at time of diagnosis) negatively influenced OS (p<.01). In a subgroup analysis of the intensive treatment group, BCR-ABL1+ patients had markedly better OS (hazard ratio 0.3, 95% CI 0.1–0.7; p<.01). In summary, despite few early deaths and a high CR/CRi rate, elderly ALL continues to have a poor prognosis, underscoring the need for more effective therapies.

The clinical outcomes of reclassified erythroleukemia (erythroid/myeloid) as myelodysplastic syndrome (MDS) per 2017 WHO guideline compared to MDS

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