A Unique Constitutional Robertsonian Translocation t(13;14) Associated with Severe Aplastic Anaemia

Aplastic anaemia is characterised by cytopenias and hypocellular bone marrow without any evidence of marrow fibrosis or marrow infiltration. There is no specific cytogenetic abnormality associated with aplastic anaemia. Most common abnormalities are trisomies of chromosome 6, 8 and loss of 7. A 17-year-old female, presented with generalised weakness, exertional breathlessness and menorrhagia for last six months. She also gave a history of 12 units Packed Red Blood Cells (PRBC) transfusion, at the rate of 2-3 units per month in the last five months. Routine haematology showed severe pancytopenia with reticulocytopenia. Bone marrow evaluation revealed hypoplastic marrow with 15% bone marrow cellularity suggesting aplastic anaemia. Karyotyping using Giemsa (GTG) banding of unstimulated culture showed a very unique constitutional Robertsonian Translocation (RT) karyotype 45+XX, der(13;14)(q10;q10). Patient responded partially to treatment with cyclosporine and anabolic steroids. The final diagnosis was severe aplastic anaemia associated with constitutional RT t(13;14) karyotype. Although cytogenetic abnormalities are neither common nor specific in aplastic anaemia, some of them can have diagnostic and therapeutic implications.

A fatal case of levamisole induced bone marrow failure

A 20-year-old college student presented with high grade, intermittent fever for 10 days associated with blood stained loose stools after taking tablet levamisole for 17 days for vitiligo vulgaris. He was febrile, had a toxic appearance and appeared pale. Investigations showed neutropaenia with thrombocytopaenia. Blood cultures were sterile and stool cultures did not grow any enteric pathogens. His bone marrow examination was suggestive of an aplastic anaemia. He was administered empirical antibiotics, granulocyte colony stimulating factor and platelet transfusions. However, his fever and blood stained stools persisted. A repeat bone marrow examination after 2 weeks still revealed a hypoplastic marrow. Hence, a diagnosis of a levamisole induced bone marrow failure was made. While being worked up for an allogeneic stem cell transplantation, he developed neutropaenic enterocolitis and refractory septic shock with carbapenem resistantKlebsiella pneumoniaeand succumbed to his illness.

PRIMARY MYELOFIBROSIS

A 55-year-old male was admitted to hospital with chief complaint of abdominal distention since one year before admission, and it became more prominent than before. The physical examination showed splenomegaly with schuffner line S5, and it was confirmed with ultrasonography. The routine blood test showed a hemoglobin level of 9.2 g/L, leukocyte count of 14.690/µL and thrombocyte count of 115 x 103/µL. From the peripheral blood smear results, the suspected diagnosis of chronic myeloid leukemia with differential diagnosis of a leukemoid reaction was made. However, bone marrow aspiration revealed hypoplastic marrow of primary myelofibrosis. The patients with primary myelofibrosis need early diagnosis and treatment to manage the symptoms of splenomegaly, stop fibrosis process and extramedullary hematopoiesis. Early treatment, in this case, can decrease poor prognosis and mortality rate.

Clinicohematological Study of Pancytopenia in a Tertiary Care Hospital of Western Region of Nepal

Introduction: Pancytopenia is a relatively common hematological entity and is a manifestation of many illnesses which can be life threatening at times. The severity of pancytopenia and the underlying pathology determine the management and prognosis. This study was conducted to evaluate hematological and bone marrow findings in patients presenting with pancytopenia. Methods: It was a prospective study carried out in Department of Pathology, Manipal College of Medical Sciences, Pokhara, Nepal, during the period of January 2011 to December 2016. Clinical and hematological parameters including bone marrow aspiration and biopsy were evaluated in all patients who presented with pancytopenia. Results: Among 138 cases studied, patient’s age ranged from 2 to 82 years with a mean age of 43.95 years, and there was male predominance. Most of the patients presented with generalized weakness, pallor, dypnoea and fever. Hypoplastic marrow was seen in 38(27.5%) cases, followed by megaloblastic anemia 26 (18.8%) cases and acute leukemia 19(13.76%) cases. Other findings included one each case of hemophagocyosis, leishmaniasis, plasmodium vivex malaria and metastatic carcinoma. Conclusions: This study highlights that pancytopenia is a common hematological problem and the study of detailed primary hematological investigations along with bone marrow study in patients with pancytopenia will help to identify the cause for further planning and management. Keywords: hypoplastic marrow; leukemia; megaloblastic anemia; pancytopenia.

Acquired aplastic anemia associated with trisomy eight converting into acute myeloid leukemia

Aplastic anemia (AA) is nowadays considered to be a clonal disorder arising from a defective hematopoietic stem cell developing after a generalized insult to bone marrow. Immunosuppressive treatment (IST) of AA causes suppression of the target dominant population of haematopoietic cells allowing the defective non targeted clones to expand. This may give rise to acute leukemia. Cytogenetic studies for chromosomal aberrations such as trisomy and monosomy may help in detecting such conversions. We present a case of acquired AA in a 60-year-old male presenting with pancytopenia and hypoplastic marrow treated with antithymocyte globulin, converting into myelodysplastic syndrome and later on acute promyelocytic leukemia after being in remission for 4 years. The patient was found to have trisomy 8 on fluorescence in situ hybridization and karyotyping.

Fanconi Anaemia – A Rare Case Report

Fanconi anaemia is a rare and most common form of inherited aplastic anaemia. It is mostly autosmal (except one x link) recessive disorder characterized by diverse congenital malformations, progressive pancytopenia, and predisposition to both haematological malignancy and solid tumours. Congenital malformation varies from patient to patient and may affect the skeletal system as well as organ systems. Highly variable phenotypic presentation with clinical menifestations makes difficult for diagnosis in some cases. Chromosomal breakage study induce by Mitomycin-C (MMC)/Diepoxybutane(DEB) provide a unique cellular marker for the diagnosis.The incidence of FA is approximately 1 to 5 per million. In Bangladesh, so far no study or even any case was reported. In this case report, a two years nine months old male child presented with generalized weakness , recurrent episodes of fever and physical deformities. It was found him short stature, microcephaly, trianguler face,generalized hyperpigmentation with café au lait spots,absent both thumbs with flexor deformity of both wrists. Peripheral smear found bicytopenia, bone marrow aspiration and biopsy showed hypoplastic marrow mildly elevated LDH, X-ray and USG showed bone and organ agenesis and chromosomal breakage study is also positive.

Decitabine Followed By Clofarabine, Idarubicin, and Cytarabine (DAC-CIA) in Relapsed/Refractory Acute Myeloid Leukemia (AML)

Background: Patients with relapsed/refractory AML have dismal outcomes with currently available chemotherapy regimens. Preclinical and clinical evidence suggests that the use of hypomethylating agents such as decitabine prior to standard chemotherapy may be synergistic (Benton et al. BJH 2014, Qin et al. CCR 2007; Scandura et al. Blood 2011). Methods: Patients aged ≥18 to 65 years with relapsed/refractory AML (up to salvage 2) were enrolled in this investigator-initiated trial (NCT01794702). Other eligibility criteria included ECOG PS 0-2 and adequate organ function. Chemotherapy regimen consisted of Induction cycle with decitabine (20 mg/m2 IV days 1-5), clofarabine (15 mg/m2 IV days 6-9), idarubicin (10 mg/m2 IV days 6-8), and cytarabine (1 gm/m2 IV days 6-10). Consolidation cycle consisted of decitabine (20 mg/m2 IV days 1-5), clofarabine (15 mg/m2 IV days 6-8), idarubicin (8 mg/m2 IV days 6-7), and cytarabine (1 gm/m2 IV days 6-8). Results: Fifty-Fourpatients (female, n=16) have been treated. Median age was 44 years (range 20-66). Majority of the patients (29/54, 54%) were in salvage 1. Cytogenetics were diploid (n=25), complex (n=15), CBF (n=5), 11q23 abnormality (n=2), trisomy 8 (n=2), inv 3 (n=2), misc (n=3). Six patients had a TP53 mutation and 6 patients had an NRAS mutation. Seven patients had NPM1 mutation. No patient had a FLT3 ITD or D835 mutation. Median number of cycles administered was 1 (range 1-3). Grade 3 mucositis was seen in 2 patients and grade 3 transaminitis in 8 patients. Thirty-three patients had one or more infections. Early deaths occurred in 4 (7%) patients within 4 weeks, and 8 (15%) patients within 8 weeks. Twenty six (48%) patients achieved CR/CRi (Table 1). Median time to CR was 42 days. An additional 3 patients had a >50% decrease in bone marrow blast count (bone marrow response) and an additional 3 patients had aplastic/hypoplastic marrow at the end of induction. Patients younger than 40 years had a significantly increased likelihood of achieving a CR/CRp/CRi (71% vs. 33%, p = 0.01) (Table 2). Eighty percent of patients with CBF AML and 64% of patients with diploid cytogenetics achieved a CR/CRp/CRi. CR rate in patients with complex cytogenetics was 20%. Twenty-five (46%) patients underwent allo-SCT (20 CR/CRp/CRi, 2 with 50% marrow blast reduction, 3 with aplastic/hypoplastic marrow). 13/21 (62%) patients younger than 40 years of age were able to undergo allo-SCT as compared to 12/33 (36%) of patients 40 years of older (p = 0.09). Ten patients have relapsed (including six after allo-SCT). Twenty patients are alive (13 after stem cell transplant, 1 is still on study, 4 are receiving further salvage regimens after DAC-CIA failure, 2 lost to follow-up). Median survival of the entire group is 6.0 months (figure 1). Conclusions: The sequential treatment of decitabine followed by chemotherapy is safe and effective with a CR/CRp/CRi rate of 48% and with 25/54 (46%) patients able to proceed to an allo-SCT. Disclosures Jain: Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Servier: Consultancy, Honoraria; Incyte: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Novimmune: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Infinity: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Abbvie: Research Funding; BMS: Research Funding. Jabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Daver:Kiromic: Research Funding; BMS: Research Funding; Pfizer: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Otsuka: Consultancy, Honoraria; Ariad: Research Funding; Karyopharm: Honoraria, Research Funding. DiNardo:Novartis: Other: advisory board, Research Funding; Daiichi Sankyo: Other: advisory board, Research Funding; Abbvie: Research Funding; Celgene: Research Funding; Agios: Other: advisory board, Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.

Three Adult Cases of HPV-B19 Infection with Concomitant Leukopenia and Low Platelet Counts

We encountered three adult patients with flu-like symptoms diagnosed with human parvovirus B19 (HPV-B19) infection. Blood serum analysis also revealed leukopenia, with white blood cell counts (WBCs) of 1,000–2,000/mL and low platelet counts of 89–150 × 109/L. Typical skin rash was absent in one patient. Bone marrow examination of another patient showed hypoplastic marrow with <5% blast cells. All patients recovered without administration of granulocyte colony-stimulating factor (G-CSF). Therefore, HPV-B19 infection with leukopenia should be considered in adult patients with leukopenia during erythema infectiosum epidemics, even if typical clinical findings (ie, skin rash) are absent. Further, the fact that three cases were observed over the stated time period at our hospital, which is located in Nagoya city, showed a transition to a slightly higher level of incidence than the annual average.

Refractory Thrombocytopenia Associated with Dengue Hemorrhagic Fever Responds to Romiplostim

Abstract 4668 Second-generation thrombopoiesis-stimulating molecules are now available, which have unique pharmacological properties and no sequence homology to endogenous TPO. Dengue is the most prevalent arthropod-borne virus affecting humans today. The virus group consists of 4 serotypes that manifest with similar symptoms and cause a spectrum of disease, ranging from a mild febrile illness to a life-threatening dengue hemorrhagic fever (DHF). Breeding sites for the mosquitoes that transmit dengue virus have proliferated, partly because of population growth and uncontrolled urbanization in tropical and subtropical countries. Dengue viruses have evolved rapidly as they have spread worldwide, and genotypes associated with increased virulence have spread across Asia and the Americas. DHF is endemic in México. We report the case of a female patient diagnosed 36 months before admission as multiple myeloma and autografted. She was admitted with a febrile syndrome diagnosed as Dengue hemorrhagic fever with severe and persistent thrombocytopenia, refractory to steroids and platelet transfusions. 56 year old lady, previosly diagnosed as multiple myeloma, treated with thalidomide, dexametasone and bortezomib until partial response. In march 2007 she was autografted using high dose melphalan (6). After autotransplant she continued using thalidomide 100 mg per day. In february 2010, 24 hours before admission to our Institution she developed nausea, vomiting, headache, fever and myalgia, no evidence of hemorrhage at physical exam. Laboratory reported positive Ag and IgM anti-Dengue virus (Platelia Dengue NS1 AG BioRad), anemia (8.3 g/dl), leukopenia (0.7 × 109/L), thrombocytopenia (17×109/L). Bone marrow aspirate and biopsy was hipocellular with mild diseritropoyesis, megaloblastic erythroid precursor cells and no evidence of myeloma. The patient was treated with intravenous hidrocortisone (300 mg/day), subcutaneous filgrastim (300 mcg/day) and antibiotics. Neutropenia resolved 4 days after starting G-CSF. Thrombocytopenia had a transient improvement and sudden fall even daily transfusions. Was treated with oprelvekin with mínimum response and serious side effects. She became refractory to allogeneic platelets ten days after first transfusion, with platelet counts between 3–10 × 109/L and severe cutaneous bleeding. Romiplostim was started (4 ug/kg/week) 55 days after severe thrombocytopenia, platelet count increased 100% in the next 48 hours with continuous elevation and no side effects. At third week of Romiplostim there was a 7 fold increase in the initial platelet count. The platelet count remains above 100 × 109/L after six dose administration with no decline in biweekly measurements. The figure shows the evolution of the platelet count before and after starting romiplostim. Steroids have been shown to be useful when DHF complicates with septic shock and even though thrombocytopenia resolves spontaneously frequently, it has been shown to be prolonged in certain circumstances. An immune mechanism of thrombocytopenia due to increased platelet destruction appears to be operative in patients with DHF; however, in the case that we are here reporting, the previous stem cell transplant and the use of thalidomide led into a hypoplastic marrow which most likely was unable to compensate the peripheral platelet destruction. The usefulness of romiplostim in this case may stem from the fact that the patients had a combined origin of the refractory thrombocytopenia, on one hand the platelet destruction induced by the dengue virus and on the other a hypoplastic marrow derived not only from the viral infection, but also from the previous stem cell allograft and the chronic use of thalidomide. Disclosures: No relevant conflicts of interest to declare.