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Objectives To estimate the risk of thrombocytopenia in various cancers and chemotherapy regimens. Methods Structured patient‐level data from the Flatiron Health Electronic Health Record database were used to identify adult patients who received chemotherapy for a solid tumor or hematologic malignancy from 2012 to 2017. Three‐month cumulative incidence of thrombocytopenia was assessed based on platelet counts, overall and by grade of thrombocytopenia. Co‐occurrence of anemia, neutropenia, and leukopenia was evaluated. Results Of 15,521 patients with solid tumors, 13% had thrombocytopenia within 3 months (platelet count

s Emerging data from the management of patients with Coronavirus Disease 2019 (COVID‐19) suggests multisystemic involvement, including the hemopoietic system. The hematological manifestations of COVID‐19 include blood count anomalies notably lymphopenia and neutrophilia which are of prognostic significance. Hyperferritinemia and elevated lactate dehydrogenase have also been associated with increased mortality. Furthermore, there is considerable evidence of a distinct coagulopathy associated with COVID‐19 characterised by elevated D‐dimers and an increased risk of thrombotic events. This comprehensive review summarises the latest evidence from published studies and discusses the implications of the various hematological manifestations of COVID‐19 with a view to guiding clinical management and risk stratification in this rapidly evolving pandemic.

Objective Autoimmune disorders, including immune cytopenia, are encountered in the setting of chronic myelomonocytic leukemia (CMML). The aim of our study was to analyze the association of immune thrombocytopenia (ITP) with chronic myelomonocytic leukemia (CMML). Methods We carried out a retrospective cohort study on 565 patients with immune thrombocytopenia (ITP) followed in the French referral center for adult's immune cytopenia. A literature review using MEDLINE (National Library of Medicine, Bethesda, MD) was also performed. Results Eight patients (5 male, 76.3 + 9.8 yr old) with ITP-associated CMML were identified in our national cohort. Thirteen cases were reported in literature from 1984 to 2013. Mean age was 65.3 ± 18.5 yr. Sex ratio (M/F) was 1/0.6. ITP unveiled CMML in all but four cases (17/21; 80.9%). ITP occurred in the setting of low-grade CMML in all cases, with neither reported progression nor acute myeloid leukemia transformation during follow-up. Overall, karyotype analysis revealed cytogenetic abnormalities in six cases (6/16; 37.5%). ITP had a chronic course in most cases and shares, according to the low level of bleeding complications and the high response rate to treatment such as corticosteroids and splenectomy, the usual characteristics of primary ITP. Conclusion Although the association of a well-defined ITP and CMML is rare, our study suggests that CMML-associated ITP should be treated according to current guidelines for primary ITP.

Introduction Myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal disorders of haematopoietic stem cells, characterised by dysplastic haematopoiesis and dysregulated apoptosis resulting in various degrees of cytopenia, whereas canonical cytologic, cytogenetic and histopathologic findings guiding the diagnosis MDS are widely accepted, the MDS-phenotype can be masked by coexisting/paraneoplastic immunologic disease. Autoimmune disorders have an estimated incidence of 10% among patients suffering from MDS and are causally related to increased morbidity and mortality, younger age at diagnosis and more complex genetics. Conversely, systemic inflammatory disorders may be an early manifestation of MDS, show good response to immunosuppressive therapy and frequently disappear during the course of specific haematologic therapy. Objective Monocentric report on clinical phenotypes found in MDS or bone marrow failure with paraneoplastic inflammatory disease. Methods Clinical case reports and systematic review about MDS pathophysiology and treatment. Results We report eight patients diagnosed with MDS or bone marrow failure, who presented with paraneoplastic autoimmune diseases. Six of eight patients were treated with the hypomethylating agent 5-azacytidine, three of which achieved meaningful response with regard to inflammation control and haematologic recovery. Conclusions As paraneoplastic syndromes are often mistakenly diagnosed as idiopathic autoimmune disorders, we propose that coexistence of an underlying myelodysplastic syndrome should be considered early in the diagnostic work up. 5-Azacytidine is effective in controlling paraneoplastic inflammation.

Objective Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition that clinically characterized by fever, hepatosplenomegaly, and cytopenia. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for patients diagnosed with primary HLH. Methods In this prospective study, we analyzed the outcome of 10 pediatric patients with primary HLH who had received HSCT, using reduced-intensity conditioning (RIC) regimen from 2007 to 2012. The median age at transplantation was 22.6 months (range: 6–60). All of the patients received the same RIC regimen based on the use of fludarabine in combination with melphalan and horse antithymocyte globulin (ATG). Cyclosporine and methylprednisolone were used as graft-vs.-host disease (GvHD) prophylaxis. Results Hematopoietic engraftment occurred in all patients. At the present time, 8 patients with a median follow-up of 39 months are still alive and all of them are disease free. Acute and chronic GvHD developed in 6 and 2 patients, retrospectively. Two patients died of sepsis and chronic GvHD during the study. Conclusion Because of pretransplant infections caused by underlying immunodeficiency in patients with primary HLH, the use of less toxic regimen with RIC seems to be highly effective in this regard. Recipients of RIC transplant, with either full or mixed chimerism, had a long-term survival rate with no manifestation of primary HLH symptoms.

Purpose Multicentric Castleman disease (MCD) is a distinct lymphoproliferative disorder characterized by inflammatory symptoms, lymphadenopathy, splenomegaly, and cytopenia. Kaposi's sarcoma-associated herpesvirus (KSHV), also called human herpesvirus-8 (HHV-8), is the cause of virtually all cases of MCD occurring in patients with HIV infection. MCD lesions characteristically contain HHV-8-infected polyclonal IgMλ plasmablasts. A high frequency of HHV-8-related non-Hodgkin lymphoma has been reported in these patients. Patients and methods We now report on three patients who presented with severe symptoms of MCD, extreme splenomegaly, and rapid expansion of B-cell lymphocytosis (44–81%) attributable to circulating HHV-8 positive plasmablasts. Results The circulating plasmablastic cells shared the phenotype (IgMλ, CD19+, CD20− CD138−) of HHV-8-infected cells from MCD lesions, mimicking the leukemic phase of large B-cell lymphoma occurring in HHV-8-related MCD. These patients displayed a very high HHV-8 viral load in blood (>7 logs HHV-8 DNA copies/ml) and high levels of serum vIL-6, the viral homolog of human interleukin 6. Serum IL-6 and IL-10 were also abnormally elevated. HHV-8-infected cells were demonstrated by immunoglobulin gene rearrangement analysis, to be polyclonal and likely represent an expansion of HHV-8-infected cells similar to those found in MCD lesions. Conclusion Thus, the spectrum of HHV-8-related plasmablastic lymphoproliferative disorders in patients with HIV infection is expanded to include HHV-8+ polyclonal IgMλ B-cell lymphocytosis. At onset, this lymphoproliferative disorder may mimic plasmablastic leukemia/lymphoma. Recognizing this unusual complication may have important implications in treatment decision avoiding unnecessary toxicity to the patients.

Copper is an essential trace element that is involved in a number of important enzymatic processes throughout the body. Recent single case reports and small studies have shown that deficiency of copper can cause reversible haematological changes and irreversible neurological injury. We chose to undertake a national study, looking at all cases of copper deficiency in Scotland over a 5-yr period using information from a national reference laboratory. From 16 identified patients, we determined that 86% had both haematological and neurological features of copper deficiency, while 18% had haematological features only at presentation. Twelve of the sixteen patients had high serum zinc concentrations (>18 μm/L) nine patients were using zinc-containing dental fixatives at time of diagnosis. 94% of patients had haematological features as an initial manifestation of copper deficiency, which included anaemia, thrombocytopenia and neutropenia. Patients who underwent later bone marrow testing had appearances in keeping with refractory cytopenia with multilineage dysplasia, refractory anaemia with excess of blasts, unclassified marrow dysplasia or probable myelodysplasia (MDS). 75% of patients had neurological symptoms or signs, including progressive walking difficulties and paraesthesia, or gait difficulties without sensory signs. Clinical examination was in keeping with spastic paraparesis (either with or without sensory neuropathy). Magnetic resonance imaging (MRI) showed multifocal T2 hyper intense foci in the subcortical white matter, and atrophy of the cerebrum and cerebellum was also seen on computerised tomography (CT). MRI of the spinal cord showed signal change in the dorsal columns in either the cervical or thoracic cord. 93% of cytopenias responded to copper replacement and addressing the original cause of the copper deficiency, but only 25% of patients had improvement in their neurological function, while 33% deteriorated and 42% remained unchanged. Our study demonstrates that copper deficiency is an under-recognised cause of several types of cytopenia, which are reversible but can progress to significant neurological injury if left untreated. We illustrate the importance of identifying these patients early to prevent irreversible neurological injury.

Introduction: Treatment with 3–6 cycles of PS-341/bortezomib, adriamycin, and dexamethasone (PAD) has been explored in terms of induction therapy prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). We evaluated the effects of two cycles of PAD given before ASCT. Patients and methods: Patients received two 21-d cycles of PAD (bortezomib 1.3 mg/m2 × 4 d, adriamycin 9 mg/m2 × 4 d, and dexamethasone 40 mg × 4 d × 2). Starting on day 12 of cycle 2, patients were given subcutaneous granulocyte-colony stimulating factor to mobilize peripheral blood stem cells (PBSCs). Following PBSC harvesting, ASCT was performed using high-dose melphalan, followed by thalidomide. Results: A total of 32 patients were enrolled. Of 31 who completed two cycles of PAD, 25 (81%) achieved a partial response (PR) or better. Major adverse events were cytopenia, with grade I/II neurotoxicity evident during 4.8% of PAD cycles. Two patients were withdrawn from the study prior to PBSC collection. Thirty patients showed successful mobilization of PBSCs and underwent ASCT, with all 30 showing adequate neutrophil and platelet recovery. Following ASCT, 14 patients (47%) achieved a complete response (CR), 8 (27%) a very good partial response (VGPR), and 6 (20%) PR. Thalidomide was given to 25 patients after ASCT, as maintenance therapy. Twelve patients showed better responses after administration of thalidomide, and a total of 21 patients (70%) achieved CR. The 5-yr probabilities of overall and progression-free survival were 71.1% and 23.5%, respectively. Conclusion: A short course of PAD was effective as an induction treatment before ASCT in patients newly diagnosed with MM. Prospective comparisons with longer courses of such treatment are needed.

Although many cytostatic drugs have been shown to be both mutagenic and carcinogenic in experimental systems, only the alkylating agents have been demonstrated with certainty to induce malignancy in man. Thus, therapy with almost all alkylating agents in clinical use today results in a highly increased risk of acute nonlymphocytic leukaemia (ANLL). Other types of leukaemia are not observed in excess following cancer chemotherapy, and only one type of solid tumour has been convincingly related to treatment with cytostatic drugs: carcinoma of the urinary bladder following cyclophosphamide and the now abandoned alkylating agent chlornaphazine. Low dose total-body irradiation, as in the atomic bomb explosions of World War II, is known to induce ANLL, acute lymphoblastic leukaemia and chronic myelogenous leukaemia, as well as various solid tumours and multiple myeloma in man. High voltage radiotherapy, by comparison, has been found to be followed by a moderately increased risk of ANLL in only a few studies. This phenomenon has been related to cell kill rather than to malignant transformation of haematopoietic stem cells within the fields of irradiation. A moderately increased risk of various solid tumours and of non-Hodgkin's lymphomas has been observed with a long follow up, particularly in series of patients treated for Hodgkin's disease. This excess possibly represents both radiotherapy-induced solid tumours and a general predisposition to development of solid tumours and non-Hodgkin's lymphomas as part of the natural history of the primary malignancy. The risk of therapy-related acute nonlymphocytic leukaemia (t-ANLL) is dose-dependent and possibly directly proportional to the total cumulative dose af alkylating agents. It increases with patient age, like the risk of de-novo ANLL, and it levels out 7–8 years after cessation of therapy with alkylating agents. Most cases of t-ANLL present in a preleukaemic phase with refractory cytopenia. Already at this early stage the characteristic chromosome abnormalities can be observed in the bone marrow, most often loss of the whole, or parts of the long arms, of chromosomes no 5 and/or no 7. The cytogenet-ic abnormalities are of diagnostic, prognostic and perhaps also of pathogenetic significance for t-ANLL.

T lymphocyte functions in acute leukaemia patients with severe chemotherapy-induced leucopenia were investigated using 3 different approaches: (i) analysis of serum concentrations of the T cell cytokine interleukin 4 (IL4) demonstrated that serum IL4 levels increased during complicating bacterial infections. However, this response was modulated by a concomitant increase in serum levels of the potential IL4 antagonist soluble IL4 receptor alpha chain (sIL4R alpha). (ii) Even during leucopenia a subset of T lymphocytes derived from leucopenic patients expressed the activation markers CD25 (IL2 receptor), CD71 (transferrin receptor) and HLA-DR. (iii) Subsets of circulating CD4+ and CD8+ T lymphocytes could undergo clonogenic proliferation in vitro, and a majority of these clones secreted IL4. CD4+ clones showed higher IL4 levels than CD8+ clones. Our results indicate that T lymphocytes can be activated and contribute to cytokine responses in acute leukaemia patients with severe chemotherapy-induced cytopenia.

We reviewed the indications for and the results of bone marrow examination (BME) from HIV-infected patients as an attempt to improve its diagnostic yield. One-hundred-and-eight bone marrow specimens from 90 patients during a 3-year period were examined. A cytological, histological and microbiological study was carried out on the specimens. Forty-three evaluable examinations (40% of total) performed for cytopenia showed normo- or hypercellularity in 33 (77%). Fifty bone marrow specimens were cultured for mycobacteria with a yield of 42% when the indication was persistent fever. Positive cultures yielded Mycobacterium avium complex in 8 out of 12 patients. Twenty-seven patients had both culture and biopsy; granulomas were associated with all the positive (10/10) and with 1 out of 17 negative cultures (chi-square test: p < 0.001). A bone marrow involvement with lymphoma was found in 2 out of 6 patients with previously diagnosed lymphoma, and biopsy revealed a lymphoma in 2 patients. Morphological bone marrow examination should be associated with other techniques in order to appreciate bone marrow production. Bone marrow biopsy is useful for the investigation of persistent fever since granulomas suggestive of disseminated mycobacteria are frequent and allow a treatment to be initiated before microbiological confirmation and antibiotic susceptibility test.

Background: Peripheral blood (PB) is sometimes used in place of bone marrow (BM) for cytogenetic studies during the evaluation of hematologic malignancies. We looked for clinical or laboratory features that predict success in obtaining analyzable metaphases during PB chromosome studies. Methods: The Mayo Clinic cytogenetics database was queried to identify adult cases (age > 18 years) with suspected or established hematologic neoplasm in whom PB cytogenetic studies were performed. Success defined as the acquisition of at least two metaphases, was correlated with clinical and laboratory information corresponding to the time of the PB cytogenetic study. Results: A total of 242 PB cytogenetic studies were performed: clinical diagnosis was a myeloid neoplasm in 169 patients (70%), lymphoid neoplasm in 50 (21%), and unexplained cytopenia or leukocytosis in 23 (9%). The 169 myeloid cases included 59 patients with either primary (n=39) or post-polycythemia vera/essential thrombocythemia (post-PV/ET MF) myelofibrosis (n=20), 42 with acute myeloid leukemia (AML), 15 with chronic myeloid leukemia, 9 with myelodysplastic syndrome (MDS), 8 with ET, 6 with PV, and 30 with other MPDs. The 50 lymphoid cases included 19 with chronic lymphocytic leukemia, 12 with lymphoma, 11 with acute lymphocytic leukemia (ALL), and 8 with plasma cell proliferative disorders. PB cytogenetic studies resulted in at least two analyzable metaphases (median 20, range 2–31) in 142 of the 242 study cases (59%); in univariate analysis, this was predicted by the specific clinical diagnosis (p Conclusion: PB cytogenetic studies are most appropriate in diseases characterized by presence of circulating myeloid progenitors or blasts (e.g. PMF, AML, ALL); the yield otherwise is too small to be cost-effective. The current study also suggests a higher likelihood of a successful PB cytogenetic study in the presence of an abnormal bone marrow karyotype.

A 36 yr-old man of Israeli descent with a history of childhood splenectomy for severe thrombocytopenia and a family history of autoimmune lymphoproliferative syndrome (ALPS), presented with severe immune thrombocytopenic purpura refractory to standard therapy. He was found to possess a heterozygous mutation in the Fas gene (also termed TNFRSF6, CD95, Apo-1) affecting the donor splice site of intron 7 (IVS7+2 T>C). This frameshift mutation truncates the cytoplasmic domain of the Fas death receptor, resulting in circulating CD4/8 double negative T lymphocytes, lymphadenopathy and autoimmune complications typical of ALPS. Administration of Rituximab in this patient was associated with a durable hematologic response (currently more than 12 months). This report highlights the need to consider rare inherited causes of thrombocytopenia in adults with a family history of immune cytopenia(s) and the effective use of anti-CD20 monoclonal antibody in patients unresponsive to immunosuppression and splenectomy.

UNLABELLED Treatment of auto-immune cytopenia refractory to front line therapy with intravenous immunoglobulins and steroids is a matter of concern. We assessed the efficacy and safety of mycophenolate mofetil in a prospective open preliminary study. STUDY DESIGN Adult patients with steroid refractory auto-immune cytopenias were included. Mycophenolate mofetil (MMF) was added to treatment given at the time of inclusion, and efficacy was evaluated in term of improvement of platelet/haemoglobin levels and in term of reduction of previously given drugs, if any. All auto-immune thrombocytopenic purpura (AITP) patients had serologic assessment for associated auto-antibodies at the time of inclusion. Cytopenias associated with other auto-immune diseases, lymphoproliferative diseases or HIV infection were excluded. RESULTS From November 1999 through November 2003, 13 patients were included (nine AITP, three auto-immune haemolytic anaemia (AIHA), one Evans' syndrome; four males, nine females; age: 35-72 yr). For AITP patients, an overall response of 78% was observed. Retrospective analysis showed no significant difference between patients having a short disease duration (

Arsenic trioxide (As2O3) therapy at a daily dose of 0.15 mg/kg was given to a 60-yr-old Japanese male with refractory acute promyelocytic leukemia. White blood cell (WBC) of 6.6 x 10(3)/microl increased to 134 x 10(3)/microl following the administration of As2O3. Daily hydroxyurea (HU), and 6-mercaptopurine (6-MP) were added on days 7 and 19, respectively. Both HU and 6-MP were discontinued on day 28, when WBC declined to 54.0 x 10(3)/microl. He developed unexplained fever and profound cytopenia requiring multiple blood products transfusions. Bone marrow examination on day 42 revealed massive necrosis. Pharmacokinetics confirmed a mean maximum plasma arsenic concentration (Cpmax) and a half-life time (t1/2) of 6.9 microm and 3.2 h, respectively, in the therapeutic range. This is the first case of bone marrow necrosis after standard-dose As2O3 therapy.

Background: Although allogeneic hematopoietic cell transplantation (HCT) has a potential to cure patients with paroxysmal nocturnal hemoglobinuria (PNH), appropriate indication and conditioning regimen for HCT have not been established. Patients and Methods: Between July 1999 and December 2001, five patients with PNH underwent allogeneic HCT: three for refractory hemolysis and two for aggravating cytopenia. Four patients with hypercellular marrow received Bu-Fludara-ATG (busulfan 4 mg/kg/d for 2 d, fludarabine 30 mg/m2/d for 6 d, and ATG 20 mg/kg/d for 4 d) for conditioning therapy and one patient with hypocellular marrow was conditioned with Cy-ATG (cyclophosphamide 50 mg/kg/d for 4 d and ATG 30 mg/kg/d for 3 d). Three patients received stem cell graft from matched sibling donor and two patients from 1-antigen mismatched unrelated donor. Results: One patient who was conditioned with Bu-Fludara-ATG failed to engraft and died at post-transplant day 62. The other four patients showed three lineage engraftment and normal expression of CD55 and CD59 antigens by flow cytometric analysis. They are alive with stable engraftment and full donor chimerism between post-transplant day 510 and 1116. Acute graft vs. host disease (GVHD) of grade II or more occurred in two patients and extensive chronic GVHD in four. Conclusion: HCT using related or unrelated donor could eradicate PNH clones and may cure patients with the disease. Further studies are needed to establish the role of allogeneic HCT, especially with reduced intensity conditioning therapy, in the treatment of PNH.

Nearly one third of patients with heparin-induced thrombo- cytopenia (HIT) will progress to overt thrombosis. Owing to the severity of HIT, a reliable prompt diagnosis is mandatory. In this study 248 consecutive samples from patients referred to our laboratory for HIT diagnosis and 97 specimens from normal controls were prospectively evaluated in parallel using the heparin-induced platelet aggregation (HIPA) test and a flow cytometric (FC) test. The HIPA test resulted in 214 negative, 17 indeterminate and 17 positive samples of patients. The FC method detects activated platelets induced by heparin-immune complexes using the highly sensitive recombinant probe annexin V and pooled platelets from multiple donors. The criteria for positive FC test results included an increase in platelet activiation of at least 11% at 0.3 IU/mL heparin concentration in the tube, and a ratio of more than 1.5 between platelet activation at 0.3 and 200 IU/mL heparin. According to the cut-off level 17 patients who showed indeteminate HIPA test results had 14 negative and 3 indeterminate corresponding FC test results. Only one of these patients (HIPA test indeterminate, FC test indeterminate) had no other obvious medical cause for thrombocytopenia than HIT. Infections or inflammations did not show any association with the FC test results, whereas thromboembolic events displayed a significant patelet activation at pharmacological heparin concentration. Therefore the FC test is associated to the complications of HIT. In conclusion, the FC test, which is fast and practical, showed a good agreement with the HIPA test and may be an accurate and useful test for HIT.

Objective: To describe the experience with liver irradiation in advanced cases of myelofibrosis with myeloid metaplasia (MMM). Methods: Over a 20-yr period, 14 patients with MMM were treated with a total of 25 courses of liver, abdominal, or abdominal and pelvic irradiation for symptomatic hepatomegaly with (5 patients) or without (9 patients) ascites. All 14 patients had advanced disease and 11 (79%) had previous splenectomy. The median radiation therapy (RT) dose per course was 150 cGy (range 50–1000) administered at a median of six fractions. Four patients received two to six courses. Results: Twelve of the 14 patients (86%) had a transient (median 3 months) subjective response from RT. However, in only 35% of these was there a transient (median 3 months) decrease in palpable liver size. Four of the five patients with ascites experienced a short-term response from RT. Eight of the 13 patients suitable for evaluation (62%) had treatment-associated cytopenia, often in the form of anemia and/or thrombocytopenia. At last follow-up, 10 patients (71%) had died after a median of 7 months (range 0.1–23) and 4 were alive at 3, 20, 33, and 57 months after RT. Conclusions: Low-dose abdominal RT for symptomatic hepatomegaly or ascites associated with advanced-stage MMM is myelosuppressive and provides only temporary and mainly subjective and short-lived relief.

A 64-yr-old patient with myelodysplastic syndrome (MDS), with refractory cytopenia with multilineage dysplasia subtype following chloramphenicol exposure received immunosuppressive treatment with antithymocyte globulin and cyclosporine (CsA). Complete remission was achieved and CsA was tapered after 2.5 yr. Shortly after CsA withdrawal, the patient relapsed with thrombocytopenia but responded to restoration of CsA. This case illustrates that immune-mediated mechanisms of cytopenia in MDS may be dependent on continued immunosuppressive treatment similar to aplastic anemia.

Background Paroxysmal nocturnal hemoglobinuria (PNH) may present as cytopenia, hemolysis, or thrombosis at unusual sites including splanchnic vessels. Thrombosis of the portal veins and hepatic veins are associated with thrombophilic risk factors: deficiencies of protein C, protein S, and antithrombin, positivity for antiphospholipid antibodies, and factor V Leiden mutation. There is limited information regarding PNH presenting primarily as a thrombotic event. We prospectively screened 142 consecutive patients with intrabdominal thrombosis and 106 controls with fluorescently labeled inactive toxin aerolysin (FLAER)-based flowcytometry to assess the frequency of PNH as a thrombophilic risk factor in patients with intra-abdominal thrombosis. Methods Granulocytes of patients and controls were screened with CD 24 and FLAER and monocytes with CD 14 and FLAER. Dual negativity of >1% events in both lineages was interpreted as a positive PNH clone. Screening for thrombophilia risk factors was carried out. Results Two (1.4%) cases had large PNH clones. RBC also demonstrated the PNH defect. Thrombophilia risk factors were as follows: deficiency of protein S, protein C, and antithrombin in 13.4%, 4.9%, and 2.1%, respectively, and positivity for anti-beta-2 glycoprotein 1, anticardiolipin antibodies, and lupus anticoagulant in 9.2%, 1.4%, and 0.7%, respectively. Factor V Leiden mutation was seen in 1.4% patients. Conclusion PNH was uncommon in patients with intra-abdominal thrombosis in the ethnic Indian population. Despite low positivity, screening by flowcytometry for PNH is of value in this group of patients because it provides an opportunity to rapidly establish the diagnosis of this treatable disorder, which might otherwise be missed if the initial presentation is only thrombotic.

Objectives Human Disabled-2 (Dab2), a putative tumor suppressor gene, is frequently down-regulated in human tumors. This study aims to explore the association between Dab2 methylation status and expression in newly diagnosed myelodysplastic syndrome (MDS) patients and patients who received 5-aza-2′-deoxycytidine (decitabine) treatment, so as to determine the effect of Dab2 in the pathogenesis of MDS. Methods Methylation-specific polymerase chain reaction and bisulfite sequencing were used to detect the methylation status of Dab2 gene. Dab2 expression was investigated by using fluorescence quantitation RT-PCR (FQRT-PCR) and western blot analysis. Results Hypermethylation of Dab2 gene was present in 50.6% of patients with MDS and was significantly correlated with the down-regulation of Dab2 mRNA and protein expression. There was a significant difference in methylation frequency between refractory anemia/refractory anemia with ringed sideroblasts/MDS associated with isolated del (5q) (RA/RARS/5q-) group (33.3%) and refractory anemia with excess blasts-1/-2 (RAEB-1/RAEB-2) group (73.3%). Significant difference was also observed between refractory cytopenia with multiline dysplasia group (37.8%) and RAEB-1/RAEB-2 group. In addition, higher frequency of hypermethylation was observed in intermediate-2-/high-risk group, compared to low-risk/intermediate-1-risk group (75.0% vs. 40.0%). Demethylating agent 5-aza-2′-deoxycytidine treatment could partly reverse hypermethylation and, hence, restore the expression of Dab2 gene. Conclusions The Dab2 gene is inactivated in MDS in part by DNA methylation, and the suppression of Dab2 expression by DNA methylation may play a role in the development of MDS.

Background Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal condition in children with Epstein–Barr virus (EBV)-associated infectious mononucleosis (IM). This study aimed to identify commonly available clinical and laboratory predictors that might help clinicians decide to perform the bone marrow and immunological tests for HLH in paediatric EBV-associated IM. Methods A retrospective case–control study of patients aged 70% of patients) were fever, lymphadenopathy and hepatomegaly. In addition to the diagnostic criteria of HLH including fever, splenomegaly, cytopenia, hyperferritinaemia, hypertriglyceridemia and/or hypofibrinogenaemia, children with HLH had a significantly higher rate of prolonged fever >10 d, hepatomegaly, jaundice, general malaise, elevated aspartate aminotransferase, lactate dehydrogenase, C-reactive protein and hypoalbuminaemia compared to those with IM (all P

Myelodysplastic syndrome (MDS) is characterized by refractory cytopenias due to ineffective hematopoiesis. Some patients with severe anemia require multiple blood transfusions and develop iron overload. Consequently, reactive oxygen species (ROS) are generated concomitant with a decrease in cellular antioxidants such as reduced gluthatione (GSH). The generated oxidative stress contributes to cell damage, apoptosis and ineffective hematopoiesis. Using flow cytometry, we measured the oxidative state of RBC, platelets and PMN in 14 low-risk MDS patients and 25 normal donors. The results indicate that the majority of the patients had higher ROS in RBC (2.79-fold) and platelets (2.91-fold) and lower GSH in their RBC (3.4-fold) and platelets (2.1-fold) than normal (p ROS generation and GSH content in MDS blood cells ROS generation and GSH content in MDS blood cells Effect of iron chelations and an antioxidant on the oxidative status of MDS cells Effect of iron chelations and an antioxidant on the oxidative status of MDS cells

Background: Splenic marginal zone lymphoma (SMZL) is an infrequent B-cell neoplasm that pursues an indolent course. Signs and symptoms, mostly related to hypersplenism, are successfully managed by splenectomy. However, the therapy of patients who are not fit for a surgical procedure or who relapse after splenectomy, is still an unsettled issue. Patients and methods: We report a phase-II study on 16 patients with SMZL, three therapy naive and 13 pretreated, all showing systemic symptoms or progressive worsening of peripheral cytopenia, who were treated with pentostatin at a dose of 4 mg/m2 every other week for 6–10 wk. In relapsed patients, the median interval between diagnosis and treatment was 26 month (range: 8–49). Results: Overall, 68% of the patients showed a clinical response. Two out three patients, who received pentostatin as first line therapy, attained a complete response (CR). One CR and seven minor or good haematological responses were recorded in relapsed patients. Treatment toxicity, mostly haematological, proved manageable. With a median follow-up of 35 month the median overall survival (OS) is 40 month and the median progression free survival (PFS) is 18 month. Conclusion: Our data show that pentostatin administered every other week has a good degree of activity in the treatment of SMZL and suggest that this schedule could be considered a possible therapeutic option for patients who are not fit for splenectomy or have relapsed.

Refractory anemia with excess of blasts (RAEB) is a myelodysplastic syndrome (MDS) characterized by cytopenia, hypercellular bone marrow, blastosis, abnormal maturation of all cell lines and a progression to acute leukemia. Immunological parameters have often been found in MDS patients, including positive direct antiglobulin test and various auto-antibodies. We describe an elderly patient with RAEB who developed clinical and biological features compatible with systemic lupus erythematosus (SLE)

The transfusional need in patients treated with myeloablative chemotherapy appears to be greater than that resulting from bone marrow suppression alone. The erythrocyte transfusional need may be expressed as delta hb = the daily loss of haemoglobin (mmol/l/day), and multivariate analyses of factors influencing delta hb have been carried out. We have studied 124 patients, mainly with acute myeloid leukaemia, treated with 537 courses of chemotherapy, inducing cytopenia (a white cell count < 1.0 x 10(9)/l) in 476 cases. The transfusional need was 2.5-3 times greater than expected, suggesting the presence of haemolysis and/or occult bleedings. Using multiple regression analysis and repeated measurement analysis the main factor influencing the transfusional need was type/dose of chemotherapy. The higher the dose of cytarabine the greater then transfusional need. Other factors significantly influencing the transfusional need were tumour burden, fever, treatment-related events such as positive blood cultures, systemic fungal infection, mucosal bleeding, melaena/haematemesis and diarrhoea. Finally, it was found that the transfusional need decreased gradually during the cytopenic period.

Hematologic abnormalities are commonly associated with infection by the human immunodeficiency virus (HIV) that is the etiologic agent of the acquired immunodeficiency syndrome (AIDS). Bone marrow examinations reveal frequent dysplasia, dyserythropoiesis, lymphocytic infiltration and plasmocytosis. These marrow morphologic characteristics are strongly associated with peripheral blood cytopenia of one or more lineage: anemia, granulocytopenia or thrombocytopenia are frequently described. The pathophysiology of these observed deficiencies is still unclear, although several mechanisms have been postulated as possible explanations for the hematological features of AIDS patients. The hematologic manifestations observed in patients with AIDS or AIDS-related complex (ARC) and the postulated pathogenetic mechanisms are discussed in this review.

10 of 20 patients with advanced myeloma treated with a simple regimen consisting of weekly low-dose cyclophosphamide (C; 150-300 mg/m2; maximum weekly dose = 500 mg) given intravenously or orally, and alternate-day oral prednisone (P; 50-100 mg) responded clinically and with a fall in serum M protein greater than 50% or urine M protein greater than 90%. 3 of these responders were previous primary treatment failures, all having received cyclophosphamide in combination with other drugs given at 3- to 4-wk intervals. 2 patients treated with this regimen as primary therapy also responded. Although the median survival for the 10 responders was reached at 24.5 months, 3 patients remain alive and well 50+ months from the start of CP therapy. An additional 5 patients had disease stabilization or major improvement in bone pain and/or pancytopenia for over 12 months despite failure to meet strict criteria for response. The data suggest that disease control may be achieved by the more frequent scheduling of known active drugs such as cyclophosphamide (although it alone or in combination with other drugs may be ineffective when given at standard 3- to 4-wk intervals) in combination with prednisone or a more continuous basis. This is an effective yet simple therapeutic approach to myeloma with the distinct advantage of less toxicity than the multiple drug regimens in current use. It may have particular applicability to patients who are elderly or debilitated or in patients in whom cytopenia is present initially or develops on standard melphalan/prednisone regimens.

Between 1980 and 1986, we diagnosed refractory anaemia (RA), according to the FAB classification, in 69 patients, who constituted 22% of the 312 cases of myelodysplastic syndromes (MDS) seen over that period. The haematological features were variable, with pancytopenia in 14 cases (20%), bicytopenia in 24 (36%) and mono-cytopenia in the remaining patients, including 21 (30%) cases of anemia alone, 8 (12%) cases of refractory neutropenia and 2 (3%) cases of refractory thrombocytopenia. Myelodysplastic features were also quite variable, involving one, two or all three lineages. In patients with a single cytopenia or only one dysplastic lineage, FAB criteria appeared insufficient for adequate inclusion among RA and we suggest more precise diagnostic criteria, resulting from the utilization of cytogenetics, ferrokinetics, progenitor cultures and perhaps molecular biology, in such cases. Median survival was 42 months. 12 patients (17%) progressed to RAEB (of whom 7 finally developed ANLL) and 4 patients (6%) to CMML. In spite of the heterogeneity of haematological features, only two factors were associated with poor prognosis, namely age greater than 70 yr at diagnosis and haemoglobin less than 10 g/dl, whereas, to a lesser extent, neutropenia was associated with progression to RAEB.