von Willebrand factor neutralizing and non-neutralizing alloantibodies in 213 subjects with type 3 von Willebrand disease enrolled in 3WINTERS-IPS.

BACKGROUND: Type 3 von Willebrand disease (VWD) is the most severe form of this disease owing to the almost complete deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived products containing VWF or recombinant VWF rarely cause the development of alloantibodies against VWF that may be accompanied by anaphylactic reactions. OBJECTIVE: The objective of this study was to assess the prevalence of anti-VWF alloantibodies in subjects with type 3 VWD enrolled in the 3WINTERS-IPS. METHODS: An indirect in-house enzyme-linked immunosorbent assay has been used to test all the alloantibodies against VWF. Neutralizing antibodies (inhibitors) have been tested with a Bethesda-based method by using a VWF collagen binding (VWF:CB) assay. Samples positive for anti-VWF antibodies were further tested with Bethesda-based methods by using the semiautomated gain-of-function glycoprotein-Ib binding (VWF:GPIbM) and a VWF antigen (VWF:Ag) enzyme-linked immunosorbent assay. RESULTS: In total, 18 of the 213 (8.4%) subjects tested positive for anti-VWF antibodies and 13 of 213 (6%) had VWF:CB inhibitors. These 13 were among the 18 with anti-VWF antibodies. Of the 5 without VWF:CB inhibitors, 3 had non-neutralizing antibodies, 1 only inhibitor against VWF:GPIbM, and one could not be tested further. Ten of the 13 subjects with VWF:CB inhibitors also had VWF:GPIbM inhibitors, 6 of whom also had VWF:Ag inhibitors. Subjects with inhibitors were homozygous for VWF null alleles (11/14), homozygous for a missense variant (1/14), or partially characterized (2/14). CONCLUSIONS: Anti-VWF antibodies were found in 8.4% of subjects with type 3 VWD, whereas neutralizing VWF inhibitors were found in 6%, mainly in subjects homozygous for VWF null alleles. Because inhibitors may be directed toward different VWF epitopes, their detection is dependent on the assay used.

Association between Perceived Stress and Neutropenia in Patients with Leukemia under Chemotherapy.

Background: The most prominent part of the cellular response of the immune system is driven by neutrophils. These cells tend to decline following chemotherapy in patients with leukemia. Neutropenia is an influential factor in the prognosis of cancer patients. Stress reduces white blood cells (WBCs) and neutrophils are linked to an increased risk of infectious diseases after chemotherapy. We investigated the association between neutropenia and perceived stress following chemotherapy. Materials and Methods: We performed a cross-sectional study on 60 patients with leukemia in a university hospital. Participants completed self-report measures, including the demographic data and perceived stress scale (PSS) questionnaire. We compared rates of neutropenia, as a measure of chemotherapy prognosis, 10 days after chemotherapy in different stress levels. Moreover, the number of patients with polymorphonuclear (PMN) under 1000/microliter was compared at different stress levels.    Results: We found that neutropenia is directly correlated with negative stress perception and inversely correlated with positive stress perception. These effects appear more prominent in patients with PMN under 1000/microliter as the number of these patients was significantly more in groups with higher negative stress and less in groups with higher positive stress scores. Conclusion: It can be concluded that stress is correlated with neutropenia, and stress management in patients with leukemia will be accompanied by better recovery outcomes and reduced risk of infectious disease.

Von Willebrand factor propeptide and pathophysiological mechanisms in European and Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS-IPS study.

BACKGROUND: Type 3 von Willebrand disease (VWD) is a severe bleeding disorder caused by the virtually complete absence of von Willebrand factor (VWF). Pathophysiological mechanisms of VWD like defective synthesis, secretion, and clearance of VWF have previously been evaluated using ratios of VWF propeptide (VWFpp) over VWF antigen (VWF:Ag) and factor (F)VIII coagulant activity (FVIII:C) over VWF:Ag. OBJECTIVE: To investigate whether the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios may also be applied to understand the pathophysiological mechanism underlying type 3 VWD and whether VWFpp is associated with bleeding severity. METHODS: European and Iranian type 3 patients were enrolled in the 3WINTERS-IPS study. Plasma samples and buffy coats were collected and a bleeding assessment tool was administered at enrolment. VWF:Ag, VWFpp, FVIII:C, and genetic analyses were performed centrally, to confirm patients' diagnoses. VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were compared among different variant classes using the Mann-Whitney test. Median differences with 95% confidence intervals (CI) were estimated using the Hodges-Lehmann method. VWFpp association with bleeding symptoms was assessed using Spearman's rank correlation. RESULTS: Homozygosity/compound heterozygosity for missense variants showed higher VWFpp level and VWFpp/VWF:Ag ratio than homozygosity/compound heterozygosity for null variants ([VWFpp median difference, 1.4 IU/dl; 95% CI, 0.2-2.7; P = .016]; [VWFpp/VWF:Ag median difference, 1.4; 95% CI, 0-4.2; P = .054]). FVIII: C/VWF:Ag ratio was similarly increased in both. VWFpp level did not correlate with the bleeding symptoms (r = .024; P = .778). CONCLUSIONS: An increased VWFpp/VWF:Ag ratio is indicative of missense variants, whereas FVIII:C/VWF:Ag ratio does not discriminate missense from null alleles. The VWFpp level was not associated with the severity of bleeding phenotype.

Reversible Acute Lung Injury due to Bleomycin.

Bleomycin is a unique antibiotic agent with cytotoxic activity and is used successfully in various malignant diseases, such as Hodgkin lymphoma and germ cell tumors. Drug-induced lung injury (DILI) is one of the major limitations of bleomycin administration in particular clinical settings. The incidence varies among patients and depends on a variety of risk factors, such as cumulative drug dose, underlying malignant disease, and concurrent radiation. The clinical presentations are non-specific for bleomycin-induced lung injury (BILI), depending on the onset and severity of symptoms. There is no established guideline for the best treatment of DILI and the treatment is based on the time and severity of pulmonary symptoms. It is important to consider BILI in any patient with pulmonary clinical manifestations who has been treated with bleomycin. Here, we report a 19-year-old woman who is a known case of Hodgkin lymphoma. She was treated with a bleomycin-containing chemotherapy regimen. On the 5th month of therapy, she was admitted to hospital with severe acute pulmonary symptoms and decreased oxygen saturation. She was treated successfully with high-dose corticosteroid without any significant sequelae.

Comparison of Long-Acting G-CSF (PD-Lasta) with Short-Acting G-CSF (PD-Grastim) in Neutrophil Recovery Following Consolidation Chemotherapy with High-Dose Cytarabine in Acute Myeloid Leukemia: A Randomized Clinical Trial.

Background: Acute myeloid leukemia (AML) patients are often neutropenic as a result of their disease alone or following their chemotherapy. In this randomized clinical trial the efficacy of Iranian short-acting (PD-Grastim) and long-acting G-CSF (PD-Lasta) were compared in term of time to recovery from neutropenia in de novo AML patients following the consolidation chemotherapy. Materials and Methods: Patients (n = 51) received one or two courses of Cytarabine and Daunorubicin as an induction. If complete remission was achieved, the treatment was followed by high-dose Cytarabine as consolidation chemotherapy. Twenty- four hours after the consolidation chemotherapy, patient were randomized to receive either daily short-acting G-CSF (PD-Grastim) (300 µg/kg) or single-dose long-acting G-CSF (PD-Lasta) (6 mg). Results: The median time to recovery of neutrophils was 11.00 and 13.00 days for short-acting G-CSF (PD-Grastim) (n=22) and long-acting G-CSF (PD-Lasta) (n=29) groups, respectively (U=186.5, P>0.05 two-tailed). Incidence of adverse effects was similar in both short-acting G-CSF (PD-Grastim) and long-acting G-CSF (PD-Lasta) groups. Conclusion: Overall, data show that Iranian long-acting G-CSF (PD-Lasta) was not significantly different with Iranian short-acting G-CSF (PD-Grastim).

Genotypes of European and Iranian patients with type 3 von Willebrand disease enrolled in 3WINTERS-IPS.

Type 3 von Willebrand disease (VWD3) is a rare and severe bleeding disorder characterized by often undetectable von Willebrand factor (VWF) plasma levels, a recessive inheritance pattern, and heterogeneous genotype. The objective of this study was to identify the VWF defects in 265 European and Iranian patients with VWD3 enrolled in 3WINTERS-IPS (Type 3 Von Willebrand International Registries Inhibitor Prospective Study). All analyses were performed in centralized laboratories. The VWF genotype was studied in 231 patients with available DNA (121 [115 families] from Europe [EU], and 110 [91 families] from Iran [IR]). Among 206 unrelated patients, 134 were homozygous (EU/IR = 57/77) and 50 were compound heterozygous (EU/IR = 43/7) for VWF variants. In 22 patients, no or only one variant was found. A total of 154 different VWF variants (EU/IR = 101/58 [5 shared]) were identified among the 379 affected alleles (EU/IR = 210/169), of which 48 (EU/IR = 18/30) were novel. The variants p.Arg1659*, p.Arg1853*, p.Arg2535*, p.Cys275Ser, and delEx1_Ex5 were found in both European and Iranian VWD3 patients. Sixty variants were identified only in a single allele (EU/IR = 50/10), whereas 18 were recurrent (≥3 patients) within 144 affected alleles. Nine large deletions and one large insertion were found. Although most variants predicted null alleles, 21% of patients carried at least 1 missense variant. VWD3 genotype was more heterogeneous in the European population than in the Iranian population, with nearly twice as many different variants. A higher number of novel variants were found in the Iranian VWD3 patients.

Genetic analysis of non-severe hemophilia A phenotype with A discrepancy between one-stage and chromogenic factor VIII activity assays.

INTRODUCTION: The diagnosis of hemophilia A (HA) is based on the measurement of factor VIII activity (VIII:C). About one-third of non-severe HA patients show a discrepancy of VIII:C measured by one-stage (VIII:C 1st) and chromogenic (VIII:C chr) assays. Different mutations in the F8 gene may cause the discrepancy in results of the FVIII activity assay. The aim of this study was to investigate F8 gene mutations in patients with assay discrepancies and to evaluate their impact on the results of VIII:C assays. METHODS: Mutation analysis was performed on 41 individuals with a discrepancy in VIII:C 1st and FVIII: C chr assays by direct sequencing. In addition, the effect of the variants on FVIII macromolecule structure was investigated by in silico and bioinformatics tools. RESULTS: Genetic analysis disclosed 22 different variants, of which 19 were identified for the first time to be involved in the phenotype of VIII:C discrepancy. Most of the variants related to the higher VIII:C 1st were found in A1, A2, A3 domains. The variant related to VIII:C chr > VIII:C 1st was located in the thrombin cleavage site. In silico analysis showed the effect of variants on FVIII macromolecule stability, which may be the possible mechanism causing the discrepancy. CONCLUSION: Our data shed light on the impact of genetic defects on VIII:C assay and provided evidence that the consideration of these mutations may open a new window to the proper diagnosis and treatment monitoring of non-severe HA patients.

Discrepancy between the results of one-stage and chromogenic factor VIII: C assays in patients with mild/moderate hemophilia A.

: Diagnosis of hemophilia A is generally based on the measurement of plasma factor VIII activity (FVIII:C) using the one-stage assay (OSA) or the two-stage chromogenic substrate assay (CSA). The results of these methods show considerable discrepancy in about one-third of non-severe hemophilia A patients. The aim of this study was to assess the prevalence of FVIII:C assay discrepancy in non-severe hemophilia A patients in Iran and the relationship between the bleeding tendency with the level of FVIII:C by each method. Patients registered as mild or moderate hemophilia A in hemophilia clinic of Imam Khomeini Hospital were included. In each patient, FVIII:C level was assessed using one-stage (FVIII:C1) and chromogenic (FVIII:CR) methods. Assay discrepancy was defined as a two-fold or greater difference between the results of two assays. Bleeding tendency of the patients was recorded based on 'ISTH-BAT'. Sixty male patients were eligible for the study. The levels of FVIII:C1 was higher than FVIII:CR in 90% of patients. Assay discrepancy was seen in 41 (68%) patients. The classification of hemophilia A in 23 (38%) patients was modified by chromogenic method. No significant correlation was noted between the results of ISTH BAT with FVIII:C levels of each method. Regarding the prevalence of FVIII:C assay discrepancy in 2/3 of our non-severe hemophilia A patients, high rate of disease severity modification by chromogenic method and no significant relation between the clinical bleeding phenotype with any method, the authors highly recommend to perform both FVIII:C assays for the diagnosis and classification of non-severe hemophilia A.

Bleeding symptoms in patients diagnosed as type 3 von Willebrand disease: Results from 3WINTERS-IPS, an international and collaborative cross-sectional study.

BACKGROUND: Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD. AIMS: To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients to investigate any possible clustering of bleeding symptoms within type 3 patients. METHODS: We compared the bleeding phenotype and computed the bleeding score (BS) using the MCMDM-1VWD bleeding questionnaire in patients enrolled in the 3WINTERS-IPS and MCMDM-1VWD studies. RESULTS: In 223 unrelated type 3 VWD patients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWD patients (15 versus 6 and 5 versus 3). Intracranial bleeding, oral cavity, hemarthroses, and deep hematomas were at least five-fold over-represented in type 3 VWD. A more severe bleeding phenotype was evident in patients having von Willebrand factor antigen levels < 20 IU/dL at diagnosis in the two merged cohorts. In type 3 patients, there was an apparent clustering of hemarthrosis with gastrointestinal bleeding and epistaxis, whereas bleeding after surgery or tooth extraction clusters with oral bleeding and menorrhagia. CONCLUSIONS: In the largest cohort of type 3 VWD patients, we were able to describe a distinct clinical phenotype that is associated with the presence of a more severe hemostatic defect.

Acute Compartment Syndrome After Knee Synovectomy in a Patient with Hemophilia A: A Case Report.

CASE: A 19-year-old man with severe hemophilia A underwent open surgical synovectomy to treat recurrent hemarthrosis of the knee. He developed symptoms and signs of acute compartment syndrome (ACS) despite receiving full-dose factor replacement. Arthrotomy was performed twice, and massive hemarthrosis was evacuated. The symptoms subsided after supplementing clotting factor with prednisone. CONCLUSIONS: ACS may complicate hemophilia. Diagnosis is mainly based on clinical judgment. Proper factor replacement is the mainstay of treatment. Surgery is reserved for patients with no improvement following factor administration.

A Double-Blind, Randomized Comparison Study between Zytux™ vs MabThera® in Treatment of CLL with FCR Regimen: Non-Inferiority Clinical Trial.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is characterized by accumulation of B cells in blood, lymphoid tissues and bone marrow. Addition of rituximab to CLL chemotherapy regimens has been associated with improved survival. The aim of this study was to establish efficacy and safety of Zytux™ in comparison to MabThera® in treatment of CLL. MATERIALS AND METHODS: Seventy CLL patients who met the criteria for entering the study were randomized into two groups (35 patients in each group). Both groups received Fludarabine and Cyclophosphamide plus Rituximab as part of the FCR regimen. Group A was treated with Zytux™, and group B was treated with MabThera®. A non-inferiority margin of 20% for the primary outcome was defined to examine the similarity between Zytux™ and MabThera®. RESULTS: Baseline demographic characteristics showed no statistically significant difference between the two groups. The two treatment groups were comparable in terms of laboratory and clinical findings, cellular index changes and CD (5, 19, 20 and 23) counts during therapy cycles and at the end of the treatment period. Regarding safety results, Zytux™ demonstrated a similar profile of adverse reactions in comparison to MabThera®. Moreover, the overall response rate was 88% and 89% for Zytux™ and MabThera®, respectively (CI -0.17, 0.18). CONCLUSION: Results showed non-inferiority of Zytux™ in terms of efficacy and adverse events as a biosimilar version of MabThera®.

Comparative evaluation of the safety and efficacy of recombinant FVIII in severe hemophilia A patients.

OBJECTIVE: This study compared the safety and efficacy of Safacto® versus xyntha® in patients with severe hemophilia A. METHODS: Thirty-three male patients with severe hemophilia A were randomly divided into two groups. Seventeen patients received Safacto® and 16 patients received Xyntha® for four consecutive times. The dosage of FVIII was 40-50 IU/kg for each injection. Plasma level of FVIII activity was evaluated before every injection, 15 minutes after the injection and one month after the start of the trial. The rate of factor VIII activity, pain and joint motion were also assessed before and after the treatment. RESULTS: Plasma level of FVIII clotting activity in Safacto® and Xyntha® were 1.96±0.5 IU/dl and 1.63±0.5 IU/dl and increased to 88.84±25.2 IU/dl and 100.09±17.8 IU/dl, respectively (P<0.001). Pain score and range of motion improvement were 9.3±0.9 and 8.7±0.1 in Safacto® (P=0.17); and 9.4±0.8 and 8.8±0.3 in Xyntha® (P=0.35), respectively. No allergic or other unfavorable reactions was observed with either of the preparations. CONCLUSION: This study showed that Safacto® has a favorable efficacy and safety profile.

In silico designing of a new cysteine analogue of hirudin variant 3 for site specific PEGylation.

Hirudin is an anticoagulant agent of the salivary glands of the medicinal leech. Recombinant hirudin (r-Hir) displays certain drawbacks including bleeding and immunogenicity. To solve these problems, cysteine-specific PEGylation has been proposed as a successful technique. However, proper selection of the appropriate cysteine residue for substitution is a critical step. This study has, for the first time, used a computational approach aimed at identifying a single potential PEGylation site for replacement by cysteine residue in the hirudin variant 3 (HV3). Homology modeling (HM) was performed using MODELLER. All non-cysteine residues of the HV3 were replaced with the cysteine. The best model was selected based on the results of discrete optimized protein energy score, PROCHECK software, and Verify3D. The receptor binding was investigated using protein-protein docking by ClusPro web tool which was then visualized using LigPlot+ software and PyMOL. Finally, multiple sequence alignment (MSA) using ClustalW software and disulfide bond prediction were performed. According to the results of HM and docking, Q33C, which was located on the surface of the protein, was the best site for PEGylation. Furthermore, MSA showed that Q33 was not a conserved residue and LigPlot+ software showed that it is not involved in the hirudin-thrombin binding pocket. Moreover, prediction softwares established that it is not involved in disulfide bond formation. In this study, for the first time, the utility of the in silico approach for creating a cysteine analogue of HV3 was introduced. Our study demonstrated that the substitution of Q33 by cysteine probably has no effect on the biological activity of the HV3. However, experimental analyses are required to confirm the results.

Evaluation of Aryoseven Safety (Recombinant Activated Factor VII) in Patients with Bleeding Disorders (An Observational Post-Marketing Surveillance Study).

BACKGROUND: Recombinant activated factor VII induces hemostasis in patients with coagulopathy disorders. AryoSeven™ as a safe Iranian Recombinant activated factor VII has been available on our market. This study was performed to establish the safety of AryoSeven on patients with coagulopathy disorder. METHODS: This single-center, descriptive, cross sectional study was carried out in Thrombus and Homeostasis Research Center ValiAsr Hospital during 2013-2014. Fifty one patients with bleeding disorders who received at least one dose of Aryoseven were enrolled. Patients' demographic data and adverse effect of drug and reaction related to Aryoseven or previous usage of Recombinant activated FVII were recorded in questionnaires. Finally data were analyzed to compare side effects of Aryoseven and other Recombinant activated FVII brands. RESULTS: Aryoseven was prescribed for 51 Patients. Of all participants with mean age 57.18+21.38 yr, 31 cases were male and 26 subjects had past history of recombinant activated FVII usage. Glanzman was the most frequent disorder followed by congenital FVII deficiency, hemophilia with inhibitors, factor 5 deficiency, acquired hemophilia, hemophilia A with inhibitor, and hemophilia A or B with inhibitor. The majority of bleeding episodes had occurred in joints. Three patients (5.9%) complained about adverse effects of Aryoseven vs. 11.5 % about adverse effects of other brands. However this difference was not significant, statistically. CONCLUSION: Based on monitor patients closely for any adverse events, we concluded that Aryoseven administration under careful weighing of benefit versus potential harm may comparable with other counterpart drugs.

JAK2V617F Allele Burden Measurement in Peripheral Blood of Iranian Patients with Myeloproliferative Neoplasms and Effect of Hydroxyurea on JAK2V617F Allele Burden.

BACKGROUND: Myeloproliferative neoplasms (MPNs) are clonal malignant diseases that represent a group of conditions including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The aim of this study was to evaluate possible correlations between JAK2V617F allele burden and clinicohematologic characteristics in Iranian patients with MPNs. We also aimed at determining the correlation between JAK2V617F allele burden and use of cyto reductive treatment (hydroxyurea). MATERIALS AND METHODS: We performed ARMS-PCR for all MPNs samples and subsequently performed real-time quantitative polymerase chain reaction (qRT-PCR) for JAK2V617F allele burden measurement using DNA from peripheral blood leukocytes. RESULTS: Two distinct groups of patients were examined at a single time point: group A (n=40; 20 PV, 20 ET) was examined at the time of diagnosis; group B (n=85; 40 PV, 30 ET and 15 PMF) while under treatment with hydroxyurea (HU). The median allele burden of the JAK2 V617F was 72% for PV and 49% for ET patients at the time of diagnosis (p=0.01). For patients with HU treatment, we determined the median JAK2V617F allele burden to be 43%, 40%, and 46.5 % in PV, ET and PMF patients; respectively. HU-treated PV patients had a significant lower %JAK2V617F than PV patients at the time of diagnosis (43% vs. 72%, p=0.005). In ET group, the relationship between the JAK2 V617F allele burden and leukocyte count was significant (p=0.02 and p=0.01 in untreated and treated patients, respectively). CONCLUSIONS: Our results showed that patients with PV have a higher JAK2V617F allele burden. Moreover, our study demonstrated that the JAK2V617F allele burden correlates with clinical features in ET group. We also showed hydroxyurea can affect the JAK2V617F allele burden in PV patients.

Prevalence and Prognostic Impact of Wilms' Tumor 1 (WT1) Gene, Including SNP rs16754 in Cytogenetically Normal Acute Myeloblastic Leukemia (CN-AML): An Iranian Experience.

BACKGROUND: The aim of this study was to evaluate the effect of Wilms' tumor 1 (WT1) gene mutations in adult cytogenetically normal acute myeloblastic leukemia (CN-AML) patients on survival and clinical outcome. PATIENTS AND METHODS: A total of 88 untreated Iranian adult patients with CN-AML were selected as a study group. Exons 7 (including the SNP rs16754), 8, and 9 as a WT1 gene hotspot region were evaluated by polymerase chain reaction and direct sequencing for detection of mutations. Response to treatment and clinical outcome including overall survival (OS) and disease-free survival (DFS) were evaluated according to WT1 gene mutational status. RESULTS: WT1 gene mutations were found in 12.5% of patients, most of which were found in exon 7. Complete remission was lower and relapse was higher in patients with WT1 gene mutation compared with WT1 gene wild type patients. OS and DFS was significantly lower in patients with WT1 gene mutation compared with patients with WT1 gene wild type (P < .001). Also, we did not find any significant effects of SNP rs16754 in exon 7 on clinical outcome and survival in patients with CN-AML. CONCLUSION: WT1 gene mutations are a predictor indicator of a poor prognosis factor in CN-AML patients. It is recommended that WT1 gene mutations be included in the molecular testing panel in order to better diagnose and confirm their prognostic significance for better management and treatment strategy.

Myelodysplastic Syndrome with 6q Deletion as the Sole Chromosome Abnormality in an Iranian Patient: A Case Report with Review of Literature.

BACKGROUND: The myelodysplastic syndrome (MDS) is a highly heterogenous disorder and karyotype analysis is helpful for diagnostic and prognostic estimation. Deletion in long arm chromosome 6 (6q del) as a sole abnormality is a rare event in MDS. This is the first case report of del (6q) as the only observed diagnostic change in Iran. We also reviewed the literature of this cytogenetic lesion.

Six-year follow up of imatinib therapy for newly diagnosed chronic myeloid leukemia in Iranian patients.

BACKGROUND: The present study reported a six-year follow up of patients with chronic myeloid leukemia who were on imatinib therapy. METHODS: We performed a retrospective study on a total of 417 patients diagnosed with chronic-phase, Philadelphia-positive (Ph+) chronic myeloid leukemia within six months before study entry. Patients were eligible for the study if they were between 18 and 70 years of age. Enrolled patients were treated at an initial dose of 400 mg of imatinib. RESULTS: The mean age of 417 patients was 40.9±14.5 years; 220 (52%) were men and 197 (47.2%) were women. Complete hematologic response at three months occurred in 99% of patients, 221 (53%) before four weeks and 196 (47%) after four weeks. Adverse events occurred in 17 (4.1%) of patients, relapse in 46 (11%) and death in 31 (7.4%) of our studied population. At 72 months, the estimated rate of overall survival rate was 89%. DISCUSSION: Our findings showed the efficacy and safety of imatinib mesylate among Iranian patients with chronic myeloid leukemia by hematological and molecular response.

Hemosuccus pancreaticus in Glanzmann thrombasthenia: implication of scintigraphy in gastrointestinal bleeding (GIB) of unknown origin.

A 33-year-old man with Glanzmann thrombasthenia, enduring retractable melena, and with an active upper gastrointestinal bleeding (GIB) of unknown origin lasting intermittently for 6 months, was admitted. Abdominal ultrasound and computed tomography were not diagnostic. The patient underwent upper gastrointestinal endoscopy twice, both of which showed blood issuing forth from ampulla of vater and possible diagnoses of bleeding from papilla/hematobilia or hemosuccus pancreaticus were suspected. Digital subtraction angiography of celiac/superior mesenteric arteries was unremarkable. In GIB scintigraphy, a focus of activity appeared in the epigastric area early in the study (arrow), intensity of which increased gradually. Exploratory laparatomy confirmed the diagnosis of hemosuccus pancreaticus. Although the patient was doing well for few weeks after the surgery, he died 3 months later after an acute episode of severe GIB.