Seasonal Human Coronavirus Respiratory Tract Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Little is known about characteristics of seasonal human coronaviruses (HCoVs) (NL63, 229E, OC43, and HKU1) after allogeneic stem cell transplantation (allo-HSCT). METHODS: This was a collaborative Spanish and European bone marrow transplantation retrospective multicenter study, which included allo-HSCT recipients (adults and children) with upper respiratory tract disease (URTD) and/or lower respiratory tract disease (LRTD) caused by seasonal HCoV diagnosed through multiplex polymerase chain reaction assays from January 2012 to January 2019. RESULTS: We included 402 allo-HSCT recipients who developed 449 HCoV URTD/LRTD episodes. Median age of recipients was 46 years (range, 0.3-73.8 years). HCoV episodes were diagnosed at a median of 222 days after transplantation. The most common HCoV subtype was OC43 (n = 170 [38%]). LRTD involvement occurred in 121 episodes (27%). HCoV infection frequently required hospitalization (18%), oxygen administration (13%), and intensive care unit (ICU) admission (3%). Three-month overall mortality after HCoV detection was 7% in the whole cohort and 16% in those with LRTD. We identified 3 conditions associated with higher mortality in recipients with LRTD: absolute lymphocyte count <0.1 × 109/mL, corticosteroid use, and ICU admission (hazard ratios: 10.8, 4.68, and 8.22, respectively; P < .01). CONCLUSIONS: Seasonal HCoV after allo-HSCT may involve LRTD in many instances, leading to a significant morbidity.

Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group.

BACKGROUND: This intercontinental study aimed to study gram-negative rod (GNR) resistance in hematopoietic stem cell transplantation (HSCT). METHODS: GNR bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were prospectively collected, and analyzed for rates and risk factors for resistance to fluoroquinolones, noncarbapenem anti-Pseudomonas ß-lactams (noncarbapenems), carbapenems, and multidrug resistance. RESULTS: Sixty-five HSCT centers from 25 countries in Europe, Australia, and Asia reported data on 655 GNR episodes and 704 pathogens in 591 patients (Enterobacteriaceae, 73%; nonfermentative rods, 24%; and 3% others). Half of GNRs were fluoroquinolone and noncarbapenem resistant; 18.5% carbapenem resistant; 35.2% multidrug resistant. The total resistance rates were higher in allogeneic HSCT (allo-HSCT) vs autologous HSCT (auto-HSCT) patients (P < .001) but similar in community-acquired infections. Noncarbapenem resistance and multidrug resistance were higher in auto-HSCT patients in centers providing vs not providing fluoroquinolone prophylaxis (P < .01). Resistance rates were higher in southeast vs northwest Europe and similar in children and adults, excluding higher fluoroquinolone- and ß-lactam/ß-lactamase inhibitor resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; noncarbapenem resistance: hospital-acquired infection, breakthrough on noncarbapenems or other antibiotics (excluding fluoroquinolones, noncarbapenems, carbapenems), donor type; carbapenem resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; multidrug resistance: longer hospitalization, breakthrough on ß-lactam/ß-lactamase inhibitors, and carbapenems. Inappropriate empiric therapy and mortality were significantly more common in infections caused by resistant bacteria. CONCLUSIONS: Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empiric antibiotic protocols. Knowledge of pathogen-specific resistance enables early appropriate empiric therapy. Monitoring of resistance is crucial. CLINICAL TRIALS REGISTRATION: NCT02257931.

Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study.

BACKGROUND: We previously reported that the "Endothelial Activation and Stress Index" (EASIX; ((creatinine×lactate dehydrogenase)÷thrombocytes)) measured before start of conditioning predicts mortality after allogeneic hematopoietic stem cell transplantation (alloSCT) when used as continuous score. For broad clinical implementation, a prospectively validated EASIX-pre cut-off is needed that defines a high-risk cohort and is easy to use. METHOD: In the current study, we first performed a retrospective cohort analysis in n=2022 alloSCT recipients and identified an optimal cut-off for predicting non-relapse mortality (NRM) as EASIX-pre=3. For cut-off validation, we conducted a multicenter prospective study with inclusion of n=317 first alloSCTs from peripheral blood stem cell in adult patients with acute leukemia, lymphoma or myelodysplastic syndrome/myeloproliferative neoplasms in the European Society for Blood and Marrow Transplantation network. RESULTS: Twenty-three % (n=74) of alloSCT recipients had EASIX-pre ≥3 taken before conditioning. NRM at 2 years was 31.1% in the high EASIX group versus 11.5% in the low EASIX group (p<0.001). Patients with high EASIX-pre also had worse 2 years overall survival (51.6% vs 70.9%; p=0.002). We were able to validate the cut-off and found that EASIX ≥3 was associated with more than twofold increased risk for NRM in multivariate analysis (HR=2.18, 95% CI 1.2 to 3.94; p=0.01). No statistically significant difference could be observed for the incidence of relapse. CONCLUSIONS: The results of this study provide a prospectively validated standard laboratory biomarker index to estimate the transplant-related mortality risk after alloSCT. EASIX ≥3 taken before conditioning identifies a population of alloSCT recipients who have a more than twofold increased risk of treatment-related mortality.

Prognostic factors impacting post-transplant outcomes in adult T-cell acute lymphoblastic leukemia: a registry-based study by the EBMT acute leukemia working party.

T-cell acute lymphoblastic leukemia (T-ALL) predominantly affects individuals in late childhood and young adulthood. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative modality particularly in the setting of poor risk genetics and/or persistent minimal residual disease. Limited studies have directly explored the impact of patient- and transplant-related factors on post-transplant outcomes in T-ALL. Using a large dataset from the European Society for Blood and Marrow Transplantation registry, we identified 1907 adult T-ALL patients (70% male) who underwent their first allo-HSCT in first complete remission (CR1) from matched sibling donors (MSD; 45%), unrelated donors (UD; 43%) or haploidentical donors (12%) between 2010 and 2021. The median age at transplant was 33.4 years (18.1-75). The median follow up was 2.9 years. Most patients underwent total body irradiation (TBI)-based myeloablative conditioning (69%). The 2-year overall survival (OS) was 69.4%, and leukemia -free survival (LFS) was 62.1%. In multivariate analysis, advanced age at transplant negatively affected LFS (for each 10-year increment, HR = 1.11, p = 0.004), GVHD-free, relapse-free survival (GRFS) (HR = 1.06, p = 0.04), OS (HR = 1.12, p = 0.002), and non-relapse mortality (NRM) (HR = 1.23, p < 0.001). More recent years of allo-HSCT were associated with improved GFRS (For each 3-year increment, HR = 0.89, p < 0.001), OS (HR = 0.9, p = 0.02), and decreased NRM (HR = 0.82, p = 0.008). TBI improved LFS. (HR = 0.79, p = 0.02), GRFS (HR = 0.83, p = 0.04), and relapse incidence (RI) (HR = 0.65, p < 0.001). Female-to-male transplant negatively affected GRFS (HR = 1.21, p = 0.02) and OS (HR = 1.23, p = 0.048). In vivo T-cell depletion significantly improved GFRS (HR = 0.74, p < 0.001). This large study identified prognostic factors, such as age at transplant conditioning regimen, in influencing post-transplant in adult T-ALL patients undergoing allo-HSCT. Importantly, a significant improvement over time was noted. These findings hold great promise for new adapted treatment strategies and can serve as a benchmark for future studies in that setting.

PTCy versus CNI-based GVHD prophylaxis in HLA-matched transplants for Hodgkin Lymphoma: a study of the LWP of the EBMT.

Studies comparing the efficacy of post-transplant cyclophosphamide (PTCy) to conventional calcineurin inhibitor (CNI)-based GVHD prophylaxis regimens in Hodgkin lymphoma (HL) patients are scarce. This study aimed to compare the outcomes of HL patients undergoing hematopoietic stem cell transplantation from HLA-matched donors who received GVHD prophylaxis with either PTCy or conventional CNI-based regimens, using data reported to the EBMT database between January 2015 and December 2022. Among the cohort, 270 recipients received conventional CNI-based prophylaxis and 176 received PTCy prophylaxis. Notably, PTCy prophylaxis was associated with delayed hematopoietic recovery, but also with a lower risk of chronic (25% versus 43%, p<0.001) and extensive chronic GVHD (13% versus 28% p=0.003) compared to the CNI-based cohort. The 2-year cumulative incidence of non-relapse mortality and relapse were 11% versus 17% (p=0.12), and 17% versus 30% (p=0.007) for PTCy and CNI-based, respectively. Moreover, the 2-year overall survival, progression-free survival and GVHD-free, relapse-free survival were all significantly better in the PTCy group compared with the CNI-based group: 85% versus 72% (p=0.005), 72% versus 53% (p<0.001), and 59% versus 31% (p<0.001), respectively. In multivariable analysis, PTCy was associated with a lower risk of chronic and extensive chronic GVHD, reduced relapse, and better OS, PFS, and GRFS compared to the CNI-based platform. Our findings suggest that PTCy as GVHD prophylaxis offers more favorable outcomes compared to conventional CNI-based prophylaxis in adult patients with HL undergoing HSCT from HLA-matched donors.

Intercontinental study on pre-engraftment and post-engraftment Gram-negative rods bacteremia in hematopoietic stem cell transplantation patients: Risk factors and association with mortality.

OBJECTIVES: We present here data on Gram-negative rods bacteremia (GNRB) rates, risk factors and associated mortality. METHODS: Data on GNRB episodes were prospectively collected in 65 allo-/67 auto-HSCT centers in 24 countries (Europe, Asia, Australia). In patients with and without GNRB, we compared: demography, underlying disease, HSCT-related data, center` fluoroquinolone prophylaxis (FQP) policy and accreditation status, and involvement of infection control team (ICT). RESULTS: The GNRB cumulative incidence among 2818 allo-HSCT was: pre-engraftment (pre-eng-allo-HSCT), 8.4 (95% CI 7-9%), post-engraftment (post-eng-allo-HSCT), 5.8% (95%CI: 5-7%); among 3152 auto-HSCT, pre-eng-auto-HSCT, 6.6% (95%CI: 6-7%), post-eng-auto-HSCT, 0.7% (95%CI: 0.4-1.1%). GNRB, especially MDR, was associated with increased mortality. Multivariate analysis revealed the following GNRB risk factors: (a) pre-eng-allo-HSCT: south-eastern Europe center location, underlying diseases not at complete remission, and cord blood source; (b) post-eng-allo-HSCT: center location not in northwestern Europe; underlying non-malignant disease, not providing FQP and never accredited. (c) pre-eng-auto-HSCT: older age, autoimmune and malignant (vs. plasma cell) disease, and ICT absence. CONCLUSIONS: Benefit of FQP should be explored in prospective studies. Increased GNRB risk in auto-HSCT patients transplanted for autoimmune diseases is worrying. Infection control and being accredited are possibly protective against bacteremia. GNRB are associated with increased mortality.

Sudden blastic crisis and additional chromosomal abnormalities during chronic myeloid leukemia in the imatinib era.

Imatinib has shown significant clinical and cytogenetic success in the treatment of chronic myeloid leukemia. Although resistance has been observed in a proportion of patients, sudden blastic crisis is a rare event during imatinib therapy. We describe a 24-year-old male patient with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who developed sudden blastic crisis in the 24th month of imatinib therapy, with loss of complete cytogenetic response. At this time, the patient had splenomegaly, severe anemia, thrombocytopenia, and leukocytosis. Bone marrow aspirate revealed the presence of massive blastic infiltration with myeloid morphology. Flow cytometric analysis of the bone marrow cells showed positivity for CD45, CD34, CD13, CD33, CD19, CD41, CD61, and glycophorin-A. Trephine biopsy specimens showed 100% cellular marrow with diffuse infiltrate by blasts. A reticulin stain of the bone marrow biopsy section demonstrated severe diffuse fibrosis. Cytogenetic analysis by fluorescence in situ hybridization (FISH) revealed that 92% of the cells were positive for the BCR/ABL fusion signal and had increased copy numbers for chromosomes 8, 13, 19, and 21. The patient's prognosis was unfavorable. In conclusion, chronic myeloid leukemia remains complex and includes unanswered questions. The presented case with a rare event during imatinib therapy highlights the need for the continued monitoring of residual disease and the development of strategies to eliminate residual leukemia cells in patients showing a complete cytogenetic response.

[Successful treatment of neuroaspergillosis in a patient with acute lymphoblastic leukemia: role of surgery, systemic antifungal therapy and intracavitary therapy]. / Akut lenfoblastik lösemili bir olguda gelisen nöroaspergillozun basarili tedavisi: cerrahi, sistemik antifungal tedavi ve intrakaviter tedavinin rolleri.

Cerebral aspergillosis is a rare condition that generally exhibits a poor response to conventional antifungal drugs. We report here a case of cerebral aspergillosis in a 34-years-old man with acute lymphoblastic leukaemia who was successfully treated with a combination of aggressive neurosurgery, intracavitary instillation of amphotericin B and voriconazole. We aimed to emphazise the roles of surgery, intracavitary therapy and antifungal therapy in the management of neuroaspergillosis. Under amphotericin-B therapy, the patient developed dysarthria and paralysis of the right side of his body. Brain magnetic resonance imaging demonstrated a lesion in the left parieto-occipital region, measuring 7 cm in the greatest dimension. Diagnostic surgery was interrupted due to abundant bleeding. The culture of the aspirate from the lesion yielded Aspergillus flavus. The therapy was switched to voriconazole and caspofungin combination. Due to disease progression during combination therapy, the patient had a second surgical resection resulting in a 75% reduction in lesion size. Following surgical intervention, intracavitary instillation of amphotericin B (0.3 mg/day for 15 days) was performed alongside with combination therapy (voriconazole and caspofungin). Caspofungin was stopped after 42 days, whereas the patient was continued on voriconazole for a total of 100 days. At this point, his brain lesion resolved almost completely. However, leukemia relapsed. The patient died during his treatment course because of neutropenic typhilitis occurring in the aplastic phase. It is stated that in patients with neuroaspergillosis radical neurosurgery leads to better outcomes if performed at an earlier stage. Antifungal treatment of cerebral aspergillosis requires that the drug must cross the blood brain barrier. Voriconazole has the ability to cross the blood brain barrier. The therapy should be prolonged beyond the resolution of all lesions and until reversal of the underlying predisposition. We conclude that the use of neurosurgery and voriconazole together appears to be a reliable and effective treatment modality in patients with cerebral aspergillosis.

Therapeutic plasma exchange plus corticosteroid for the treatment of the thrombotic thrombocytopenic purpura: a single institutional experience in the southern Marmara region of Turkey.

Thrombotic thrombocytopenic purpura (TTP) is a classic, but not a common disorder of hematology. Plasma exchange (PE) was shown to nearly reverse its 90% mortality rate. However, there are still some fatal outcomes in this dramatic disease. We present our experience of plasma exchange plus corticosteroids for the treatment of TTP in our hospital. Patients with TTP diagnosed between January 1996 and January 2005 were identified by a retrospective review of records of the Uludag University Hospital, Bursa (the largest referral center for adults with this disorder in this region with an estimated 2.2 million residents), which performs all therapeutic PE in the southern Marmara region in Turkey. A total of 11 (6 male, 5 female) patients were treated for TTP during this period. The median age was 39 years (range 18-49). One plasma volume exchange daily plus steroid was the principle treatment in all patients. A total of 295 PE sessions were performed. We have obtained six complete responses (CR) and three partial responses (PR) with daily PE and steroid (response rate 9/11). One of our primary refractory patients was saved with pulse steroid+cyclosporine+vincristine. Now, he is disease free for over one year. The other refractory patient did not develop any response to salvage therapy and expired on day 15 with status epilepticus and ventilator related pneumonia (mortality rate 1/11). A CR was obtained with adjuvant treatments in all three PR patients. Only one CR patient developed an early relapse (early relapse rate in CR patients 1/6). She was treated successfully with daily PE plus vincristine. Our median follow up period was 25 months (range 9-108). Considering our local population, our annual incidence is only about 0.63 new cases per one million people. This figure is considerably less than the data from US, which indicated an incidence of 3.7 cases per 1,000,000. To our knowledge, there is no high variability in the incidence of TTP in the different geographical regions of the world. It suggests that considerable number of patients escaped notice. We hope that, demonstrating the successful outcome, this article serves to urge primary physicians to keep in mind the diagnosis of TTP and refer suspected cases quickly.

Invasive pulmonary aspergillosis: role of early diagnosis and surgical treatment in patients with acute leukemia.

BACKGROUND: Aspergillus is a ubiquitous soil-dwelling fungus known to cause significant pulmonary infection in immunocompromised patients. The incidence of aspergillosis has increased during the past two decades and is a frequently lethal complication of acute leukemia patients that occurs following both chemotherapy and bone marrow transplantation. The diagnosis of invasive pulmonary aspergillosis (IPA) according to the criteria that are established by European Organization for the Research and Treatment of Cancer and Mycoses Study Group raise difficulties in severely ill patients. Despite established improvements in field of diagnosis (galactomannan antigen, quantitative PCR, real-time PCR for Aspergillus spp., and findings of computed tomography) and treatment with new antifungals, it is still a major problem in patients with acute leukemia. However, prompt and effective treatment of IPA is crucial because most patients will need subsequent chemotherapy for underlying hematologic disease as soon as possible. CASE PRESENTATION: We report a 33-year-old male patient with acute promyelocytic leukemia diagnosed in 1993 that developed invasive pulmonary aspergillosis due to A. flavus at relapse in 2003. The patient was successfully treated with liposomal amphotericin B and underwent surgical pulmonary resection. The operative course was uneventful. CONCLUSION: This report emphasizes the clinical picture, applicability of recent advances in diagnostic and therapeutic approaches for IPA. For early identification of a patient infected with IPA, a high index of suspicion and careful clinical and radiological examinations with serial screening for galactomannan should be established. If aspergillosis is suspected, anti-aspergillosis drug should be administered immediately, and if a unique pulmonary lesion remains, surgical resection should be considered to prevent reactivation during consecutive chemotherapy courses and to improve the outcome.

Hydatid disease in acute leukemia: effect of anticancer treatment on echinococcosis.

Echinococcosis, also known as hydatid disease or hydatidosis, is a zoonotic illness caused by the larval form of Echinococcus spp. It is highly prevalent in areas where the parasite is endemic such as the Mediterranean region. However, occurrence of echinococcosis and cancer together is rare. We treated and followed approximately 1200 patients with different hematologic neoplastic diseases between 1985 and 2003, and only one of these individuals had concomitant acute leukemia and liver hydatidosis. This report describes the case of a 19-year-old man who had both primary refractoriness of acute leukemia (AML-M4) and liver hydatidosis. Management is discussed. The patient had cystic echinococcosis (CE) of the liver that was classified as CE1 according to the system established by the World Health Organization's Informal Working Group on Echinococcosis. The patient underwent 3 months of treatment with agents that targeted the leukemia (daunorubicin, idarubicin, cytarabine, fludarabine) and its complications (amphotericin B, amphotericin B lipid complex, liposomal amphotericin B). Throughout this period, the size and the contents of the cyst did not change, Echinococcus titers remained unchanged, and the cyst classification remained CE1.

Pregnancy under treatment of imatinib and successful labor in a patient with chronic myelogenous leukemia (CML). Outcome of discontinuation of imatinib therapy after achieving a molecular remission.

Because of the teratogenicity data in rats, it is recommended that women treated with imatinib should be aware of the potential teratogenicity of imatinib and effective contraception should be used during imatinib therapy to prevent pregnancy. We describe successful pregnancy and delivery, without any congenital anomaly, in a patient with CML under treatment of imatinib. The fetus had been exposed to imatinib for 8 weeks. The patient remained off treatment during gestation and cytogenetic relapse of CML (5 months after discontinuation of imatinib therapy) developed at seventh month of gestation.

The bone marrow aspirate and biopsy in the diagnosis of unsuspected nonhematologic malignancy: a clinical study of 19 cases.

BACKGROUND: Although bone marrow metastases can be found commonly in some malignant tumors, diagnosing a nonhematologic malignancy from marrow is not a usual event. METHODS: To underscore the value of bone marrow aspiration and biopsy as a short cut in establishing a diagnosis for disseminated tumors, we reviewed 19 patients with nonhematologic malignancies who initially had diagnosis from bone marrow. RESULTS: The main indications for bone marrow examination were microangiopathic hemolytic anemia (MAHA), leukoerythroblastosis (LEB) and unexplained cytopenias. Bone marrow aspiration was not diagnostic due to dry tap or inadequate material in 6 cases. Biopsy results were parallel to the cytological ones in all cases except one; however a meticulous second examination of the biopsy confirmed the cytologic diagnosis in this patient too. The most common histologic subtype was adenocarcinoma, and after all the clinical and laboratory evaluations, the primary focus was disclosed definitively in ten patients (5 stomach, 3 prostate, 1 lung, 1 muscle) and probably in four patients (3 gastrointestinal tract, 1 lung). All work up failed in five patients and these cases were classified as tumor of unknown origin (TUO). CONCLUSION: Our series showed that anemia, thrombocytopenia, elevated red cell distribution width (RDW) and hypoproteinemia formed a uniform tetrad in patients with disseminated tumors that were diagnosed via bone marrow examination. The prognosis of patients was very poor and survivals were only a few days or weeks (except for 4 patients whose survivals were longer). We concluded that MAHA, LEB and unexplained cytopenias are strong indicators of the necessity of bone marrow examination. Because of the very short survival of many patients, all investigational procedures should be judged in view of their rationality, and should be focused on treatable primary tumors.

Serum galactomannan levels in the diagnosis of invasive aspergillosis.

BACKGROUND/AIMS: In this study, the sensitivity-specificity of galactomannan-enzyme immunoassay (GM-EIA) with a cut-off value of 0.5 for a single, two, or three consecutive positivity in the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients with hematological malignancy was investigated. METHODS: IPA was classified as "proven," "probable," or "possible" as described in the guidelines prepared by the European Organization for Research and Treatment of Cancer and Mycoses Study Group." Serum samples were collected from the patients twice a week throughout their hospitalization. A total of 1,385 serum samples, with an average of 8.3 samples per episode, were examined. RESULTS: Based on the 165 febrile episodes in 106 patients, 80 (48.5%) were classified as IPA (4 proven, 11 probable, 65 possible) and 85 (51.5%) as non-IPA. The sensitivity/ specificity was 100%/27.1% for a single proven/probable IPA with the cut of value of GM-EIA ≥ 0.5, 86.7%/71.8% for two consecutive positive results, and 73.3%/85.9% for three consecutive positive results. CONCLUSIONS: With the galactomannan levels measured twice a week, consecutive sensitivity decreased and specificity increased. Therefore, an increase may be obtained in sensitivity-specificity by more frequent monitoring of GM-EIA starting from the first day of positivity is detected.

Comparison of genetic changes between interphase and metaphase nuclei in monitoring CML and APL treatment using DC-FISH technique.

In leukemias, the monitoring techniques on the response after the treatment have clinical importance for evaluating new therapeutic approaches and identifying the risk of relapse. In this study, genetic changes before and after chemotherapy in interphase and metaphase nuclei of bone morrow of adults with provisional diagnosis of leukemia were compared to understand the molecular characterization and pathogenesis of the leukemia for the classification of diagnosis and prognosis. We examined bone morrow cells of 47 chronic myeloid leukemia (CML) cases (29 of 47 at the time of diagnosis, 31 of 47 after chemotherapy) with the bcr/abl translocation probes and of 10 acute promyelocytic leukemia (APL) cases (7 of 10 at the time of diagnosis, 4 of 10 after chemotherapy) with the PML/RARalpha translocation probes by using dual color-flourescence in situ hybridization (DC-FISH). For each case, 400 interphase nuclei and 11 to 25 metaphases nuclei were analysed. The ratios of translocations before and after chemotherapy were compared between interphase and metaphase nuclei. After chemotherapy, though, translocations were detected in interphase nuclei of 29 of the 31 CML and 4 of the 4 APL cases, these translocations were determined in metaphase nuclei of only 14 of the 31 CML and 1 of the 4 APL cases with very low ratios (p < 0.01). The results showed that the rates of translocation positive interphase nuclei were higher than the rates of translocation positive metaphase nuclei (p < 0.01) after chemotherapy, so there may be some factors effecting proliferative activity of metaphase formation in leukemias.

Maternal and fetal outcomes in pregnancy complicated with acute leukemia: a single institutional experience with 10 pregnancies at 16 years.

The incidence of acute leukemia in pregnancy is low and the management of acute leukemia during pregnancy is difficult. We have observed a total of 10 pregnancies in 8 patients. Six of the patients had acute myeloblastic leukemia (AML) and two of them had acute lymphoblastic leukemia (ALL). Three of the pregnancies were diagnosed when the leukemia was in remission, six at the time of leukemia diagnosis and one at the time of leukemic relapse. Six of the pregnancies were found in first trimester, three in the second and one early in the third. Three pregnancies ended with spontaneous abortion, three with intrauterine death and three with medical termination. One of spontaneous abortions and one intrauterine death developed during combination chemotherapy (daunorubicin, cytarabine). Only 1 healthy baby survived from the 10 pregnancies and this child was the not exposed to chemotherapeutic agents. None of the cases had gynecologic and obstetric complications. Five of eight pregnant women with leukemia died because of the primary disease.

Tuberculosis presenting as immune thrombocytopenic purpura.

BACKGROUND: Although various hematologic abnormalities are seen in tuberculosis, immune thrombocytopenic purpura is a rare event. CASE PRESENTATION: We report a case of a 29 year-old male who was presented with immune thrombocytopenia-induced hemoptysis, macroscopic hematuria and generalized petechiae. The patient was found to have clinical, microbiological and radiological evidence of active pulmonary tuberculosis. The immune thrombocytopenic purpura was successfully treated with anti-tuberculous drugs combined with corticosteroids and high dose immune globulin therapy. CONCLUSION: Immune thrombocytopenic purpura can be one of the hematological manifestations of tuberculosis which has a global prevalence with increasing incidence secondary to HIV infection.

A case of granulocytic sarcoma during complete remission of acute myeloid leukemia with multiple masses involving the larynx and nasopharynx.

A thirty-seven-year-old male patient presented with dysphagia and hoarseness six months after complete remission of acute myeloid leukemia (AML-M0), which had been treated with chemotherapy. Physical examination revealed left vocal cord paralysis and involvement of the 9th, 10th, and 12th cranial nerves. Sagittal and axial magnetic resonance scans of the nasopharynx and neck showed a mass in the left retropharyngeal and perivertebral regions, 6x4 cm in size; another mass in the left vallecula, and infiltration of the right preepiglottic tissue by another mass of 2 cm. There was no bone marrow involvement. A diagnosis of granulocytic sarcoma without leukemia relapse was made and the FLAG-Ida regimen was administered, after which partial regression of the masses was observed. However, the patient died due to a pulmonary infection on the 17th day of chemotherapy.