COVID-19 infection in patients with acute leukemia; Istanbul experience.

Coronavirus disease 2019 (COVID-19) has led to a global pandemic that has also challenged the management of various other life-threatening conditions, such as malignant disorders. In this study, we present the clinical features and treatment outcomes of twenty-seven COVID-19 positive patients with leukemia across seven different centers in Istanbul. From March 1st to December 31st 2020, 116 patients were diagnosed with acute leukemia. Thirty-two cases with acute lymphocytic leukemia (ALL), 82 cases with acute myeloid leukemia (AML), and 2 cases with mixed phenotype acute leukemia (MPAL) were identified. Of the 27 patients with the COVID-19 infection, seven patients had ALL, 19 patients had AML and one patient had MPAL. The mortality rate was 37% among the patients with AML, whereas there were no deaths in the ALL group. The mortality rate of AML patients with the COVID-19 infection was higher compared to cases without the infection (P<0.05). We could not detect any significant difference in the ALL cohort. This study, which includes one of the largest acute leukemia series in literature proved that acute myeloid leukemia patients with the COVID-19 infection have worse outcomes than patients without the infection. The high mortality among patients with acute leukemias hospitalized with COVID-19 highlight the need for aggressive infection prevention, increased surveillance and protective isolation and even modification of the therapy, in case of minimal residual disease (MRD) negativity.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.

A chronic myeloid leukemia case with a variant translocation t(11;22) (q23;q11.2): masked Philadelphia or simple variant translocation?

Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia chromosome (Ph), usually due to a reciprocal translocation, t(9;22)(q34;q11.2). The remaining cases (2-10%) have variant translocation, and more rarely (~1%) a cryptic rearrangement is present which can be detected by fluorescence in situ hybridization analysis in a CML patient with a Ph-negative karyotype (Masked Ph). We present a masked/variant BCL-ABL-positive CML patient showing a t(11;22)(q23;q11.2) which was detected using a combined approach of conventional cytogenetics and reverse transcription polymerase chain reaction. In February 2013, the patient was diagnosed as having CML. Imatinib mesylate (400 mg/day), was then started. Under imatinib therapy a complete hematologic and cytogenetic response was attained. In December 2013, an increment in BCR-ABL/ABL transcript levels according to the International Scale (from 0.0471% to 1.4034%), indicating imatinib failure, was documented. Administration of nilotinib (400 mg twice daily) resulted in durable molecular response after 3 months. The patient is still on nilotinib treatment throughout the observation period with no sign of recurrence and adverse events.

Assessment of Endothelial Dysfunction With Flow-Mediated Dilatation in Myeloproliferative Disorders.

BACKGROUND: Thrombosis is the most important cardiovascular complication of classical myeloproliferative disorders (MPDs). Endothelial dysfunction (ED) is known to play a major role in the mechanism of thrombophilia in MPDs. METHODS: Endothelial dysfunction and its associations with other parameters were investigated. A total of 18 patients with polycythemia vera (PV), 24 with essential thrombocytosis (ET), 7 with primary myelofibrosis (PMF), and 30 healthy patients as a control group were included in the study. To assess the ED, flow-mediated dilatation (FMD) measurements were used. RESULTS: The FMD (%) result showing ED was determined as 9.9 (0.0-21.6) in the patients with PV, 7.3 (0.0-30.5) in patients with ET, 7.5 (0.0-18.0) in patients with PMF, and 13.9 (6.2-26.7) in the control group. The FMD (%) was markedly impaired in all patients with MPD compared to the control patients (7.8 [0.0-30.5] vs 13.9 [6.15-26.8], P = .02). According to the disease subtypes, FMD (%) was significantly lower in the ET group than in the control group ( P = .01). CONCLUSION: Endothelial function was assessed in patients with MPD having FMD and was determined to demonstrate ED. Lower FMD was associated with older age, leukocytosis, thrombocytosis, and thrombosis history.

Splenic artery embolization with Ankaferd blood stopper in a sheep model.

PURPOSE: Splenic artery embolization is a minimally invasive therapeutic procedure utilized in a number of disorders. Ankaferd blood stopper (ABS) is a novel hemostatic agent with a new mechanism of action independent of clotting factors. We aimed to investigate the safety and efficiency of ABS for splenic artery embolization in a sheep model. METHODS: Seven adult female sheep were included in the study. Selective celiac angiography was performed using a 5F diagnostic catheter and then a 2.7F hydrophilic coating microcatheter was advanced coaxially to the distal part of the main splenic artery. Under fluoroscopic guidance, 6 mL mixture composed of half-and-half ABS and contrast agent was slowly injected. Fluoroscopy was used to observe the deceleration and stagnation of the flow. Control celiac angiograms were obtained immediately after the embolization. After the procedure, the animals were observed for one day and then sacrificed with intravenous sodium thiopental. RESULTS: Technical success rate was 100%. None of the animals died or experienced a major systemic adverse event during the procedure. All of the spleens appeared dark on macroscopic examination due to excessive thrombosis. Microscopically, the majority of the splenic sinusoids (90%-95%) were necrotic. CONCLUSION: In our study, splenic artery embolization by ABS was found to be safe and effective in the short-term. Further studies are needed to better understand the embolizing potential of this novel hemostatic agent.

The Prognosis of Adult Burkitt's Cell Leukemia in Real-Life Clinical Practice.

OBJECTIVE: Many studies reported an improved prognosis in patients with Burkitt's lymphoma obviating the need of stem cell transplantation. However, prognosis of the advanced disease [i.e. Burkitt's cell leukemia (BCL)] has not been reported with current treatment modalities except for a few prospective trials. The aim of this study is to compare the prognoses of BCL patients with similarly treated and nontransplanted patients with other types of acute lymphoblastic leukemia (ALL) and with ALL patients that underwent allogeneic stem cell transplantation (ASCT) in their first remissions. MATERIALS AND METHODS: In this retrospective analysis, BCL patients aged between 16 and 63 who were admitted between 2000 and 2014 to the hospitals of Hacettepe or Gazi University and were treated with intensive therapies aimed at cure were included. All ALL patients who were treated with a similar protocol not including transplantation during the same period (NT-ALL group) and all ALL patients who underwent ASCT in the first complete remission during the same period (T-ALL group) served as control groups. RESULTS: The central nervous system or extramedullary involvement rates, lactate dehydrogenase levels, and white blood cell counts at diagnosis were higher in the BCL group than the NT-ALL group and these differences were significant. BCL patients had disease-free survival (DFS) durations comparable with the T-ALL cohort but NT-ALL patients had significantly shorter DFS durations. Both cumulative relapse incidence and cumulative nonrelapse mortality were higher in NT-ALL patients compared to the T-ALL group and BCL patients. CONCLUSION: DFS in BCL patients treated with a widely accepted modern regimen, R-HyperCVAD, is comparable to results in other ALL patients receiving allogeneic transplantation. Our results are in agreement with a few prospective noncomparative studies suggesting no further need for stem cell transplantation in BCL.

A Rare Cause of Cavitary Lesion in the Lung: Richter's Transformation.

Richter's transformation (RT) refers to the development of aggressive lymphoma during the course of CLL. Clinically, patients with RT present with an aggressive disease course with rapidly enlarging lymph nodes, hepatosplenomegaly, and elevated serum lactate dehydrogenase levels. But rarely it presents with extra nodal organ involvement at the beginning. Common sites of extra nodal involvement are the gastrointestinal tract, eye, central nervous system, lung, and kidney. We are reporting this case that was presented with RT in the lung involvement diagnosed while researching cavitary lesion etiology.

A proven case of cutaneous rhizopus infection presenting with severe limb pain very soon after induction treatment in a patient with acute lymphoblastic leukemia.

Objective and Importance. Invasive mucormycosis may complicate the course of patients with hematologic malignancies and has a very high mortality rate. Early diagnosis and aggressive approach combined with surgical and medical treatment have paramount importance for cure. Clinical Presentation. We report here a case of a patient with acute lymphoblastic leukemia presenting with a subcutaneous mass lesion which was sampled by an ultrasound guided needle biopsy. The pathology showed microorganisms with aseptate hyphae with wide, irregular walls and more or less branching with highly vertical angles which suggested a mold infection. The specimen was also cultured where Rhizopus spp. grew. Conclusion. Posaconazole 200 mg QID was commenced. She recovered from neutropenia and pain on day 20 of treatment. After 4 courses of hyper-CVAD chemotherapy, the remaining soft tissue mass was removed surgically and she underwent allogeneic HSCT from a full matched sibling donor under secondary prophylaxis.

Factors associated with cytomegalovirus reactivation following allogeneic hematopoietic stem cell transplantation: human leukocyte antigens might be among the risk factors.

OBJECTIVE: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. Current practice includes prophylactic and preemptive treatment modalities, which have risks, side effects, and costs of their own. There is no established risk scoring system that applies to all patients. We aimed to investigate the risk factors for CMV reactivation in AHSCT recipients. MATERIALS AND METHODS: We retrospectively analyzed the risk factors for CMV reactivation in 185 consequent AHSCT recipients transplanted between September 2003 and December 2009 at the Stem Cell Transplantation Unit of Gazi University. Besides the standard transplant-related parameters, HLA antigens were also included among the variables analyzed. RESULTS: Despite the very high rate of donor (94.6%) and recipient (100%) seropositivity, which are the so-called major risk factors in previous reports, our reactivation rate was much lower, with a frequency of 24.9%. The underlying disease, sex, conditioning regimen, and presence of antithymocyte globulin or fludarabine in the conditioning regimen had no impact on reactivation rate. CMV reactivation was significantly more frequent in recipients with graft-versus-host disease (GVHD) compared to those without GVHD (p<0.0001). CMV reactivation was significantly more frequent (p<0.05) in patients with HLA-B14, HLA-DRB1*01, and HLA-DRB1*13 antigens and less frequent in recipients with HLA-A11 and HLA-DRB1*04 antigens (p<0.05). CONCLUSION: Universal risk factors/scores that apply to all transplant recipients are required for tailored prophylaxis and/or treatment strategies for CMV reactivation. Uncovering the role of genetic factors, including HLA antigens, as possible risk factors might lead the way to risk-adaptive strategies for adoptive cellular therapy and/or vaccination.

A rare case of acute leukemia relapsing with a granulocytic sarcoma causing ectopic pregnancy.

A 33 year old female was admitted to department of obstetric and gynaecology with profuse vaginal bleeding. She was diagnosed with acute myeloid leukemia 3 months ago. Pelvic ultrasound was unremarkable. Since vaginal bleeding persisted despite normal platelet counts low dose methotrexate was administered with the presumptive diagnosis of ectopic pregnancy. A laparoscopic investigation was performed as she did not respond to this treatment which revealed an intraluminal ectopic pregnancy in her right fallopian tube. A pathological specimen was obtained. Granulocytic sarcoma is an infiltrate of immature granulocytic precursor cells in an extramedullary site. To best of our knowledge, this case is the third patient with GS in the fallopian tube and the first case causing ectopic pregnancy.

The intensive care management process in patients with hematopoietic stem cell transplantation and factors affecting their prognosis.

OBJECTIVES: Hematopoietic stem cell transplantation (HSCT) recipients may require further management in intensive care unit (ICU). The ICU outcome of the HSCT recipients is claimed to have improved significantly over the last two decades. Our aim was to investigate the ICU outcome of the HSCT recipients who required management in ICU, together with the factors that are likely to affect the results. MATERIALS AND METHODS: We retrospectively investigated the ICU outcome of 48 adults (≥18 years of age) who received HSCT in the bone marrow transplant unit of our hospital and required admission to ICU between 01 January 2007 and 31 December 2010. The data were retrieved from the databases of the adult bone marrow transplantation unit and the ICU. RESULTS: Sixty-one percent of the patients were male with a median age of 39 years (28-46.75) in the study cohort. Leukemia (54%) and lymphoma (27%) were the leading underlying disorders. The type of HSCT was autologous in 14.6% and allogeneic in 85.4% of the patients. The reason for admission to ICU was acute respiratory failure in 85.5% of the HSCT recipients and 75% had sepsis/septic shock. The mean duration of ICU stay was 104.5 (48-168) hours. Sixty-nine percent of the patients died during their ICU stay while 31% survived. Besides the several statistically significant differences between the patients who survived or died in ICU in univariate analysis, baseline Acute Physiology and Chronic Health Evaluation (APACHE II) score (odds ratio 1.38, 95% confidence interval: 1.06-1.79) and requirement of vasopressors in the ICU (odds ratio 72.29, 95% confidence interval:4.47-1169.91) were found to be independent risk factors for mortality in multivariate analysis. CONCLUSION: Baseline APACHE II score and requirement of vasopressors during ICU stay were the most significant independent risk factors for mortality in HSCT recipients who required ICU management in our center.

Thrombotic thrombocytopenic purpura secondary to ABO group incompatible blood transfusion in a patient after cardiac surgery.

The triggers of secondary thrombotic thrombopcytopenic purpura (TTP) include drug toxicity, radiation and high-dose chemotherapy, angioinvasive infections, surgery and acute graft versus host disease. TTP secondary to surgery have been reported in a number of cases. Most of the cases have been occurred after open heart surgery. Extensive endothelial damage is held responsible as the initiating mechanism in postoperative TTP cases. However, there is no report of secondary TTP describing development owing to ABO incompatible blood transfusion. Here, we describe a patient who developed TTP after transfusion of ABO incompatible blood during hospitalization for bypass surgery. We also propose a hypothesis which may account for the possible underlying mechanism.

Hyper-CVAD regimen in routine management of adult acute lymphoblastic leukemia: a retrospective multicenter study.

Treatment of acute lymphoblastic leukemia is unsatisfactory in adults due to disease and patient-related factors and probably because adult chemotherapy regimens are weaker than pediatric protocols. Worries about inadequacy of adult regimens urged many hematologists, including us, to reconsider their routine treatment practices. In this retrospective multicenter study, we aimed to evaluate results of hyper-CVAD treatment in comparison to other intensive protocols. All patients aged ≤65 years who were commenced on intensive induction chemotherapy between 1999 and 2011 were included in the study. Sixty-eight of 166 patients received hyper-CVAD, 65 were treated with CALGB-8811 regimen and 33 with multiple other protocols. Limited number of patients who were treated with other intensive protocols and mature B-acute lymphoblastic leukemia cases who were mostly given hyper-CVAD were eliminated from the statistical analyses. In spite of a favorable complete remission rate (84.2%), overall (26.3 vs. 44.2% at 5 years, p = 0.05) and disease-free (24.9 vs. 48.2%, p = 0.001) survival rates were inferior with hyper-CVAD compared to CALGB-8811 due to higher cumulative nonrelapse mortality risk (29.7 vs. 5.9%, p = 0.003) and no superiority in cumulative relapse incidence comparison (45% for both arms, p = 0.44). Hyper-CVAD, in its original form, was a less favorable regimen in our practice.

Outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin lymphoma patients in a centre from Turkey.

PURPOSE: The aim of this study is to assess the predictors of outcome in patients with relapsed or refractory Hodgkin's lymphoma (HL) receiving autologous stem-cell transplantation (ASCT) MATERIALS AND METHODS: Fifty-two consecutive patients who received ASCT at the Stem Cell Transplantation Unit of Gazi University Hospital from February 2005 through June 2011 for relapsed or refractory HL were analysed retrospectively RESULTS: Fifty-one patients could be evaluated after transplantation, as one of the patients died in the early post-transplantation period. Complete remission was obtained in 36 (71%), partial remission in 9 (18%), stable disease in 4 (8%), and progressive disease in 2 (3%) patients. After a median follow-up of 22 (range, 0.5-75) months, 46 (88%) patients were alive. The probability of overall survival (OS), progression free survival (PFS) and transplantation related mortality at 5 years were 87, 53, and 2%, respectively. Chemosensitive relapse had a positive impact on both OS and PFS CONCLUSION: ASCT remains to be the standard treatment of relapsed or refractory HL patients. Chemosensitive relapse is the most important prognostic factor determining the outcome of the ASCT.

Short-term effects of Ankaferd hemostat for renal artery embolization: an experimental study.

PURPOSE: Renal artery embolization (RAE) is a minimally invasive therapeutic technique that is utilized in a number of disorders. Ankaferd is a novel hemostatic agent with a new mechanism of action independent of clotting factors. We used Ankaferd for RAE in a sheep model. METHODS: Seven adult female sheep were included in the study. Selective renal arteriogram using 5-F diagnostic catheter was performed to make sure that each kidney was fed by a single renal artery and the animal had normal renal vasculature. Coaxial 2.7-F microcatheter was advanced to the distal main renal artery. Under fluoroscopic guidance, 2 mL of Ankaferd mixed with 2 mL of nonionic iodinated contrast agent was slowly injected. Fluoroscopy was used to observe the deceleration of flow and stagnation. Control renal angiograms were performed just after embolization. After the procedure, the animals were observed for 1 day and then sacrificed with intravenous sodium thiopental. RESULTS: The technical success was observed in seven of the seven animals.. After embolization procedure, none of the animals died or experienced a major systemic adverse event. On macroscopic examination of the embolized kidneys, thrombus at the level of main renal artery formed after Ankaferd embolization was more compact compared with the thrombi that was not Ankaferd-associated, which was observed elsewhere. Microscopically, majority of the renal tubular cells (80-90 %) were necrotic, and there was epithelial cell damage in a small portion of the cells (10-20 %). CONCLUSIONS: RAE was safe and effective in the short-term with Ankaferd in studied animals. Further studies should be conducted to better delineate the embolizing potential of this novel hemostatic agent.

Heparin-induced thrombocytopenia in a hemodialysis patient treated with fondaparinux: nephrologists between two fires.

Heparin-induced thrombocytopenia (HIT) is caused by heparin exposure and presents with reduced platelet count. Patients undergoing hemodialysis (HD) treatment have increased risk of developing HIT due to prolonged exposure to unfractionated heparin or low-molecular weight heparin. We report a 79-year-old male patient with end-stage renal disease who developed type-II HIT during maintenance HD. Platelet count of the patient decreased gradually and antiplatelet factor IV antibody was found to be positive. The patient was treated with fondaparinux and continued heparin-free HD. Unfortunately, despite favorable initial response without any thrombotic episodes, the patient died due to severe sepsis complicated by gastrointestinal hemorrhage.

HBV-related events after allogeneic hematopoetic stem cell transplantation in a center from Turkey.

To investigate the frequency of hepatitis B virus (HBV)-related events after allogeneic HCT in a moderate endemic area for HBV infection. The data of 197 patients who underwent allogeneic hematopoetic stem cell transplatation (HCT) from September 2003 through December 2010 were reviewed retrospectively with respect to HBV-related events. Resolved HBV infection was described as negative HBsAg, positive HBcAb, and positive HBsAb. Latent HBV infection was defined in patients with HBcAb positivity in the abscence of HBV DNA and HBsAb. Hepatitis B naive patients are defined as the patiens with no serological or molecular marker related to HBV. Seropositive patients were the patients with positive HBsAg and HBV-DNA. Median age was 28 (range, 15-64) years, with 128 male and 69 female patients. Median follow-up of the cohort was 8 (range, 0.5-78) months. We detected HBV-related events in 7 (3.6 %) recipients after allogeneic HCT. Five (71.4 %) of these events were HBV reactivation, while two cases (28.6 %) had acute hepatitis B infection. Four of the five reactivations were in the seropositive group (80 %), while one ocurred in a patient with resolved hepatitis. Two patients who developed acute hepatitis B were HBV naive and previously immunized patients, respectively. Hepatitis B virus reactivation remains a problem in seropositive patients and might require more effective treatment strategies.