Transient bone marrow hypoplasia preceding T-Cell acute lymphoblastic leukemia: a case report

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and is characterised by hy- perproliferation of malignant lymphocytes in the bone marrow. Rarely, ALL may be preceded by a period of pancytopenia and bone marrow hypoplasia which spontaneously recovers. This phenomenon, which has not before been described in T-cell ALL, is referred to as transient bone marrow hypoplasia. Case presentation: A 5-year-old boy who presented with high-grade fever and generalised lymphadenopathy, was found to have pancytopenia on peripheral blood count and bone marrow hypoplasia. He was observed over a one-month period during which his bone marrow and peripheral blood counts recovered spontaneously. Symptoms recurred after 4 months and he was found to have blast infiltration of the bone marrow and diagnosed with T-cell ALL. Conclusion: Cases of transient bone marrow hypoplasia or overt aplastic anemia with spontaneous recovery and then followed by B-cell ALL or Acute Myeloid Leukemia have been described previously in the medical literature. This is the first case of transient bone marrow hypoplasia resulting into ALL of T-cell immunophenotype. While marrow hypoplasia preceding ALL remains poorly understood, it suggests an antecedent environmental insult to lymphoid progenitors or a germline abnormality that predisposes to lymphoid dysplasia. This may provide clues to the hitherto unknown pathophysi- ological process and etiological factors that precede the majority of childhood ALL cases. This case enlightens pediatricians about the existence of such rare cases so as to periodically follow up children with pancytopenia and/or bone marrow hy- poplasia for prolonged periods even after apparent recovery. Keywords: Pancytopenia, hypoplasia; aplastic anemia; T-cell acute lymphoblastic leukemia; case report.

Persistent Neutropenia after ABOi Kidney Transplantation: A Case Report

Post-transplant neutropenia (PTN) is frequently reported in the first-year after transplantation. Although prevalence and clinical consequences are widely described, there are no guidelines to manage diagnosis and treatment. We report here a case of persistent PTN occurred in a patient undergoing a kidney transplant from an AB0-incompatible living donor. The desensitization protocol consisted of Rituximab administration and immunoadsorption while the pre-transplant protocol, which was initiated 14 days before the transplant, included Tacrolimus, Mofetil Mycophenolate (MMF), antimicrobial and antiviral prophylaxis. Induction therapy consisted of anti-thymocyte globulins and steroids, while maintenance after transplantation consisted of steroid, tacrolimus and MMF. When the first occurrence of leukopenia was observed six weeks after the transplant, firstly antimicrobial/antiviral prophylaxis was stopped and later also MMF treatment was interrupted but severe neutropenia relapsed after MMF resuming treatment. Immunological and virological causes were excluded. The patient was treated with Filgrastim. Bone marrow biopsy, which was performed to exclude a hematological cause of severe persistent neutropenia, revealed a bone marrow hypoplasia with neutrophils maturation interrupted at the early stages. This case highlights the need to establish diagnostic and therapeutic guidelines for PTN which take in consideration all the therapeutic steps including the pre-transplant phase in particular in the context of AB0i where immunosuppression is more consistent.

The impact of environmental lead exposure on Whooper swan (Cygnus cygnus): Pathological and immunohistochemical studies

This study was carried out to investigate the pathology of environmental lead (Pb) poisoning in Whooper swans (Cygnus cygnus). A number of 12 out 54 swans (22.2%) randomly collected from Honshu, Japan from June 2005 to July 2007 were affected with Pb poisoning. Affected swans showed stained vent with greenish watery diarrhoea and impacted crop. The presence of Pb shots in the gizzard (50%) was confirmed by X-ray, and all cases showed a dark greenish coloured liver. Microscopically, the pathology of Pb poisoning in swans was multisystemic. The severity of the lesions was the highest in the CNS followed by the liver, kidney, spleen, lungs, gizzard, heart, bone marrow respectively and was the least in the peripheral nervous system. CNS lesions were cerebral haemorrhage, malacia, and spongiosis with astrocytic activation and increased neurofilaments accumulations. In addition, there were hepatic and renal hemosiderosis and apoptosis, hepatic granuloma, interstitial pneumonia, gizzard and myocardial necrosis and bone marrow hypoplasia. Chemical analysis of the Pb content in liver and kidneys ranged from 8.18 to 60.6 µg/g, respectively. The extent and severity of lesions varied among individuals and were mostly dose-dependent. Finally, these findings improved the diagnostic procedure of Pb poisoning in free-living Whooper swans.

Paclitaxel-induced disorders in hematopoietic progenitor cells as a possible cause of the development of distant genoand myelotoxicity in CBA mice

Выявлено генотоксичное воздействие паклитаксела на хромосомный материал дифференцированных клеток костного мозга самцов и самок мышей в ранние и отдаленные сроки исследования. Установлено, что в эти же сроки наблюдения паклитаксел вызывает гипоплазию костного мозга и снижает в костном мозге экспериментальных животных количество ранних клеток-предшественников эритропоэза, а также способствует уменьшению их пролиферативного потенциала независимо от пола. The genotoxic effect of paclitaxel on the chromosomal material of differentiated bone marrow cells in male and female mice was revealed in the early and long-term periods of the study. It was found that during the same observation period paclitaxel causes bone marrow hypoplasia and reduces the number of early erythropoiesis progenitor cells in the bone marrow of experimental animals, and also contributes to a decrease in their proliferative potential regardless of gender.

Hepatitis-associated Aplastic Anaemia in Children

Background Children with idiopathic acute liver failure (IALF) are at a high risk of developing life-threatening bone marrow failure (BMF). The aim of the study was to describe the development, therapy and prognosis of this hepatitis-associated aplastic anaemia (HAAA) in comparison to isolated acquired aplastic anaemia. Results We retrospectively found 18 patients (9 female) of HAAA between 1984 and 2017 with an age of 1.4–16.4 years. Fifteen of them fulfilled the SAA criteria, 3 had a bone marrow hypoplasia. Eleven of these children received liver transplantation (LTx) (these were 11 of 42 (26%) children receiving LTx for IALF), 6 patients recovered without LTx. The first signs of BMF, thrombocytopaenia and leucocytopaenia, occurred before LTx in all cases. During the follow-up period 8 patients reached haematological remission, 6 received haematopoietic stem cell transplantation (HSCT). Seven children died in a median of 304 days after the first symptoms mostly because of bleedings and infections. To date, extensive investigations failed to detect a genetically, viral or immunological aetiology. No AA was diagnosed in the 41 patients receiving liver transplants during the same period for ALF of known aetiology. As a comparison group, we collected the data of patients with isolated SAA. 73% achieved a remission after Immunosuppressive therapy (IST) without HSCT, and none of them died during the follow-up period. Conclusion Blood counts should be examined early and regularly (0–22 days after onset) in patients with IALF. Aggressive treatment with LTx, IST and HSCT appears to improve the prognosis.

Aplasia in Chronic Phase CML Post-TKI Therapy: A Management Dilemma

Transient cytopenias and bone marrow hypoplasia commonly occur during treatment of CML with TKIs (tyrosine kinase inhibitors). This is usually related to the eradication of CML clones that initially compose the majority of hematopoietic cells in the bone marrow at the time of diagnosis. With continuation of effective therapy, normal blood counts return as normal hematopoiesis is restored and CML clones are reduced. Though rare and more unusual than myelodysplastic syndrome (MDS), isolated instances of persistent marrow aplasia have been documented with chronic use of TKIs. We describe two such instances of chronic phase CML where no significant reduction of CML clones was achieved following treatment with TKIs, but bone marrow aplasia occurred resulting in persistent dysfunctional hematopoiesis. Due to prolonged aplasia/hypoplasia, such patients are no longer amenable to TKI treatment. CML progression to accelerated or blast phase in that setting would likely be fatal.