Incidence of Silent Thrombosis in Patients Younger Than 60 Years With Myeloproliferative Neoplasms: Single-Center Egyptian Study.

BACKGROUND: Identification of janus kinase 2 (JAK2) mutation even in absence of myeloproliferative disorders (MPNs) was found to be related to venous thromboembolism occurrence. Venous thrombosis screening is not routinely requested in patients with myeloproliferative neoplasms unless the patient is symptomatic. It has been reported that the incidence of thrombosis in elderly patients is much higher than in young patients. The aim of this work was to screen MPN patients for venous thrombosis and study its correlation with JAK2 allele burden and with MPN 10 score. PATIENTS AND METHODS: We enrolled 73 patients with JAK2-positive MPN from our Hematology Clinic in the period August 2015 to Feb 2017. All patients had been screened for thrombosis in the venous system in lower limbs (LLs), upper limbs, portal, and mesenteric systems using color Doppler ultrasound imaging. RESULTS: Fifty-three (72.6%) patients were younger than 60 years. Twenty-two (30%) had essential thrombocytosis, 35 (47.9%) had polycythemia rubra vera, and 16 (22%) had idiopathic myelofibrosis. Twenty-seven venous thrombotic attacks were reported in 22 (30.1%) patients. Five (6.8%) had thrombosis in 2 sites. Seventeen (23%) had superior mesenteric and portal vein thrombosis. Six (8%) had iliofemoral (8%) and 4 (5%) had combined LL and portal thrombosis. Eight (10.8%) had active thrombosis at screening. Only 3 patients (4%) were symptomatic with abdominal pain during screening. Pruritis (P = .02) and abdominal pain (P = .039) were significantly different between cases with and without thrombosis. There was no significant difference in MPN 10 score between cases with active or previous thrombosis. CONCLUSION: We recommend routine screening for venous thrombosis in any case of MPN when diagnosed and screening for MPNs in any patient with venous thrombosis especially of the portal vein or atypical sites. If MPN patients present with increasing pruritus or abdominal pain, they also should be screened for venous thrombosis. Further research on a large scale in MPN age groups younger than 60 years regarding pathogenesis of thrombosis is highly recommended.

Role of physical function in predicting short-term treatment outcome in Egyptian acute myeloid leukemia patients: a single center experience

Abstract Background Acute myeloid leukemia (AML) is a potentially fatal hematological disease. Along with disease-related factors, patient-related factors, in particular age, are a strong predictor of outcome that influence treatment decisions. Many acute myeloid leukemia risk stratification models have been developed to predict the outcome of intensive chemotherapy. However, these models did not include physical function assessments. Methods This study investigated the impact of several factors, namely the performance status, physical function and age on the short-term outcomes of intensive chemotherapy in a cohort of 50 Egyptian patients with de novo acute myeloid leukemia. Results Complete remission after intensive chemotherapy in these myeloid leukemia patients at Day 28 was 56% and the mortality rate was 12% and 34% at Day 28 and Day 60, respectively. The pretreatment Eastern Cooperative Oncology Group score was significantly correlated with outcomes on Day 28 and Day 60 (p-value = 0.041 and p-value = 0.032, respectively). There were significant correlations between the two-minute walk test and outcomes of therapy on Day 28 and 60 (p-value = 0.032 and p-value = 0.047, respectively) and between grip strength test and outcomes of therapy on Day 28 and 60 (p-value = 0.046 and p-value = 0.047 respectively). Furthermore, there was a significant correlation between chair stand test and outcome of therapy on Day 28 (p-value = 0.023). Conclusion Performance status and physical function assessments were strong predictors of outcome of intensive chemotherapy in acute myeloid leukemia and we recommend the incorporation of these variables in risk stratification models for the personalization of therapy before treating acute myeloid leukemia patients with intensive chemotherapy.

Role of physical function in predicting short-term treatment outcome in Egyptian acute myeloid leukemia patients: a single center experience.

BACKGROUND: Acute myeloid leukemia (AML) is a potentially fatal hematological disease. Along with disease-related factors, patient-related factors, in particular age, are a strong predictor of outcome that influence treatment decisions. Many acute myeloid leukemia risk stratification models have been developed to predict the outcome of intensive chemotherapy. However, these models did not include physical function assessments. METHODS: This study investigated the impact of several factors, namely the performance status, physical function and age on the short-term outcomes of intensive chemotherapy in a cohort of 50 Egyptian patients with de novo acute myeloid leukemia. RESULTS: Complete remission after intensive chemotherapy in these myeloid leukemia patients at Day 28 was 56% and the mortality rate was 12% and 34% at Day 28 and Day 60, respectively. The pretreatment Eastern Cooperative Oncology Group score was significantly correlated with outcomes on Day 28 and Day 60 (p-value = 0.041 and p-value = 0.032, respectively). There were significant correlations between the two-minute walk test and outcomes of therapy on Day 28 and 60 (p-value = 0.032 and p-value = 0.047, respectively) and between grip strength test and outcomes of therapy on Day 28 and 60 (p-value = 0.046 and p-value = 0.047 respectively). Furthermore, there was a significant correlation between chair stand test and outcome of therapy on Day 28 (p-value = 0.023). CONCLUSION: Performance status and physical function assessments were strong predictors of outcome of intensive chemotherapy in acute myeloid leukemia and we recommend the incorporation of these variables in risk stratification models for the personalization of therapy before treating acute myeloid leukemia patients with intensive chemotherapy.

Role of Granulocyte-Macrophage Colony-Stimulating Factor in Acute Myeloid Leukemia/Myelodysplastic Syndromes.

PURPOSE: Granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine stimulates growth, differentiation, and function of myeloid progenitors. We aimed to study the role of GM-CSF gene expression, its protein, and antibodies in patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) and their correlation to disease behavior and treatment outcome. The study included 50 Egyptian patients with AML/MDS in addition to 20 healthy volunteers as control subjects. PATIENTS AND METHODS: Assessment of GM-CSF gene expression was performed by quantitative real-time polymerase chain reaction. GM-CSF proteins and antibodies were assessed by enzyme-linked immunosorbent assay. RESULTS: There was significant decrease in GM-CSF gene expression ( P = .008), increase in serum level of GM-CSF protein ( P = .0001), and increase in anti-GM-CSF antibodies ( P = .001) in patients with AML/MDS compared with healthy control subjects. In addition, there was a significant negative correlation between serum levels of GM-CSF protein and initial peripheral blood blasts, percentage as well as response to therapy. CONCLUSION: Any alteration in GM-CSF gene expression could have implications in leukemogenesis. In addition, GM-CSF protein serum levels could be used to predict outcome of therapy. GM-CSF antibodies may also play a role in the pathogenesis of AML/MDS. The use of these GM-CSF parameters for disease monitoring and as markers of disease activity needs further research.

MPN10 score and survival of molecularly annotated myeloproliferative neoplasm patients.

JAK2, CALR, MPL and triple-negative mutational status has a direct impact on symptom severity and disease burden assessed by MPN10 score in myeloproliferative neoplasms (MPNs). Among 93 patients; median MPN10 score was 48 (5-76) in JAK2 mutants versus 25 (4-80) in JAK2 negative (p < .001); 22.5 (4-65) in CALR mutants versus 35 (5-80) in CALR negative (p < .050) and 21 (10-48) in triple negative versus 40 (4-80) in JAK2/CALR/MPL mutants (p < .001). At three years, progression free and overall survival of JAK2-positive versus JAK2-negative patients were 62% versus 100% (p < .001); 85% versus 100% (p = .011) and were 100% versus 78% (p = .067); 100% versus 92% (p = .197) in CALR-positive versus CALR-negative patients and 100% versus 75% (p = .004); 100% versus 90% (p = .015) in triple negative versus mutant patients, respectively. MPN10 score in association with driver gene mutations can be used as a predictor of survival in MPN patients.

Correlation between JAK2 allele burden and pulmonary arterial hypertension and hematological parameters in Philadelphia negative JAK2 positive myeloproliferative neoplasms. An Egyptian experience.

Myeloproliferative neoplasms are characterized by a common stem cell-derived clonal proliferation, but are phenotypically diverse. JAK2 is mutated (V617F) in more than 90 % of patients with polycythemia vera (PV) and approximately 60 % of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Pulmonary arterial hypertension (PAH) is a major complication of several hematological disorders. Chronic myeloproliferative disorders associated with PAH have been included in group five for which the etiology is unclear and/or multifactorial. The aim of this study is to screen Egyptian Philadelphia negative JAK2 positive myeloproliferative neoplasm patients for the presence of PAH and its correlation with JAK2 allele burden. We also made a review for correlation of JAK2 allele with hematological parameters comparing our results to others. We enrolled 60 patients with Philadelphia negative myeloproliferative neoplasms. All patients enrolled in the study were subjected to laboratory and imaging workup in the form of CBC, liver, kidney profile, bone marrow examination, abdominal ultrasonography, and transthoracic echocardiography. Our results revealed that 7 patients out of 60 (11.67 %) had pulmonary arterial hypertension, 3 patients with PMF, 2 patients with PRV, and 2 patients with ET, and its correlation with JAK2 allele burden was not statistically significant. Correlation analysis between JAK2 V617F allele burden and other parameters revealed: statistical significant correlation with age, HB, HCT, PLT, UA, LDH, and splenic diameter but insignificant correlation with WBCs and PAH. Pulmonary arterial hypertension prevalence in our study was 11.67 % and no significant correlation with JAK 2 allele burden. Our study is the largest one up to our knowledge that studies the association between its prevalence and JAK2 burden.

Predictive Value of Pretreatment BCR-ABL(IS) Transcript level on Response to Imatinib Therapy in Egyptian Patients with Chronic Phase Chronic Myeloid Leukemia (CPCML).

BACKGROUND: A wide range of responses of patients with CPCML to IM has been reported. Several factors were proposed to predict response including molecular response at 3 and 6 months. PURPOSE: To study the impact of pretreatment BCR-ABL transcript level on molecular response to IM, and to assess the value of the milestone ; ≤10% transcript at 3 months on PFS and OS. PATIENTS AND METHODS: Fifty five adult CP-CML patients receiving daily dose of 400 mg IM were subjected to molecular and cytogenetic analysis at diagnosis and at regular time intervals. Median follow up period was 36 months (15-48). Hematologic, cytogenetic, and molecular responses were rated according to ELN. RESULTS: Two Patient groups were distinguished regarding response to IM therapy. A group of 22/55 patients (40%) having pretreatment BCR-ABL(IS) level ≤200% and a second patient group 33/55 (60%) having transcript level >200%. The ≤10% milestone was achieved by 15/22 patients (68%) versus 7/33 patients (21%), p=0.04 in favor of the first group. Optimal responders in first group were 14/22 (64%) compared to 13/33 (39%) in second group, p=0.02. Achievement of 10% transcript level significantly correlated with longer PFS. The median BCR-ABL(IS) transcripts levels in optimal responders at 3, 6 and 18 months was 10%, 2% and 0.1%, respectively compared to 100%, 65% and 10%, in suboptimal/resistant patients p=0.001. Resistance in 11 patients was correlated with identifiable ABL Kinase mutations. CONCLUSIONS: The Pretreatment 200% cutoff and the 3 month BCR-ABL(IS) ≤10% transcript levels proved strong predictors of response to IM and significantly correlated with probability of CCyR, MMR and PFS.

Prevalence of occult hepatitis C virus in egyptian patients with chronic lymphoproliferative disorders.

Background. Occult hepatitis C virus infection (OCI) was identified as a new form of Hepatitis C virus (HCV), characterized by undetectable HCV antibodies and HCV RNA in serum, while HCV RNA is detectable in liver and peripheral blood cells only. Aim. The aim of this study was to investigate the occurrence of OCI in Egyptian patients with lymphoproliferative disorders (LPDs) and to compare its prevalence with that of HCV in those patients. Subjects and Methods. The current study included 100 subjects, 50 of them were newly diagnosed cases having different lymphoproliferative disorders (patients group), and 50 were apparently healthy volunteers (controls group). HCV antibodies were detected by ELISA, HCV RNA was detected in serum and peripheral blood mononuclear cells (PBMCs) by reverse transcription polymerase chain reaction(RT-PCR), and HCV genotype was detected by INNO-LiPA. Results. OCI was detected in 20% of patients group, compared to only 4% OCI in controls group. HCV was detected in 26% of patients group with a slightly higher prevalence. There was a male predominance in both HCV and OCI. All HCV positive patients were genotype 4. Conclusion. Our data revealed occurrence of occult HCV infection in Egyptian LPD patients at a prevalence of 20% compared to 26% of HCV.

Aggressive cutaneous vasculitis in a patient with chronic lymphatic leukemia following granulocyte colony stimulating factor injection: a case report.

INTRODUCTION: Vasculitis has been reported in a few cases of chronic lymphatic leukemia and with granulocytic colony-stimulating factor therapy. Those with granulocytic colony-stimulating factor occurred after prolonged therapy and there was a rise in total leukocyte count unlike that in our patient who received just a single injection for the first time. CASE PRESENTATION: We report the case of a 64-year-old Egyptian man with chronic lymphatic leukemia who developed progressive cutaneous vasculitic lesions following injection of a single dose of a granulocytic colony stimulating factor before a third cycle of chemotherapy to improve neutropenia. This is an unusual case and the pathogenesis is not fully understood. Our patient was not on any medical treatment except for bisoprolol for ischemic heart disease. Although aggressive management with steroids, anticoagulation and plasmapheresis had been carried out, the condition was aggressive and the patient's consciousness deteriorated. A magnetic resonance imaging scan of his brain revealed multiple ischemic foci that could be attributed to vasculitis of the brain. CONCLUSION: The aim of this case report is to highlight the importance of monitoring patients on granulocytic colony-stimulating factor therapy, especially in the context of other conditions (such as a hematological malignancy) that may lead to an adverse outcome.

Cost and outcome of treatment of adults with acute myeloid leukemia at the National Cancer Institute-Egypt.

BACKGROUND: Despite important advances in the therapy of acute myeloid leukemia (AML), the majority of patients die of their disease, unless bone marrow transplantation (BMT) is done. Infection and hemorrhage are still the major causes of mortality in AML patients. Progress in therapy and supportive care has led to gradual improvement in the overall results, but further improvements are still needed. PATIENTS AND METHODS: The aim of this study is to identify the outcome and costs of adult AML patients treated with conventional chemotherapy (CCT) at the National Cancer Institute (NCI), Cairo University during the time period from April 1999 to January 2002. Clinical, laboratory characteristics were all recorded. Data regarding different types of therapies given for these patients including response, outcome and costs were also collected. RESULTS: The median age of 82 identified AML patients was 34 years. The complete remission (CR) rate after induction with CCT was 52% (42/82 patients) with a median CR duration of 9 months. Twenty-eight percent of patients who achieved CR subsequently relapsed. By January 2003, fifty-eight patients were dead (70.7%). Infections were the major mortality cause, followed by disease progression then bleeding (65% , 28% and 7% respectively). The median treatment cost per patient was 33158 Egyptian Pounds (LE). It was higher for patients who achieved CR compared to those who relapsed and/or died. Drugs contributed by 78 % to the total treatment cost, while hospitalization, investigations and blood-component therapy contributed by 6%, 7% and 8% respectively. CONCLUSIONS: Outcome of patients with AML treated at NCI- Cairo University can be enhanced by improvement of supportive therapy; mainly infection control and expanding BMT programs to accommodate all eligible patients.