Kensuke Kojima

Life-threatening bleeding and acquired factor V deficiency associated with primary systemic amyloidosis

Acquired factor X deficiency has been described in patients with amyloidosis but acquired factor V deficiency is quite rare. We report here a case of life-threatening bleeding and acquired factor V deficiency associated with primary amyloidosis. A 50-year-old man who had no previous hemorrhagic diathesis was referred to our hospital because of recurrent epistaxis, gingival bleeding and hemospermia. The laboratory examination revealed that both the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) were significantly prolonged, and factor V activities were markedly decreased to 14-39% of the normal value. Other coagulation factors such as fibrinogen, prothrombin, factor VII, factor VIII, factor IX and factor X were subnormal and normal. Transaminases were slightly elevated but serological tests of hepatitis B and hepatitis C were negative. Mild hepatosplenomegaly was noted without sign of liver cirrhosis. The PT and aPTT obtained 8 years ago when he received a cholecystectomy due to cholecystitis were both normal. Specific assays for the detection of factor V inhibitor were repeatedly performed but no factor V inhibitor was found. Furthermore, a significant recovery of the infused factor V was noted shortly after an intravenous administration of 5-10 U fresh frozen plasma, but it did not last more than 6 h. Melena, bleedings into the left shoulder and buttock, and finally mortal retroperitoneal hemorrhage developed despite repeated infusions of large amounts of fresh frozen plasma. Acquired factor V deficiency associated with primary amyloidosis was suspected but histological diagnosis was not obtained because of the severe bleeding tendency. Autopsy revealed hepatosplenomegaly and massive deposits of AL amyloid in the liver, spleen, heart and other parenchymal organs. Perivascular amyloid deposition and factor V deficiency are both thought to be the cause of the severe hemorrhagic tendency seen in this patient.

Predictive value of circulating immature cell counts in peripheral blood for timing of peripheral blood progenitor cell collection after G–CSF plus chemotherapy-induced mobilization

BACKGROUND: Enumeration of CD34+ cells in peripheral blood (PB) before apheresis predicts the number of CD34+ cells collected, although flow cytometric techniques used are complex and expensive. In an attempt to determine the optimal timing for peripheral blood progenitor cell (PBPC) collection, the usefulness of circulating immature cell (CIC) counts in PB was evaluated.

T-cell receptor γδ T-cell leukemia with the morphology of T-cell prolymphocytic leukemia and a postthymic immunophenotype

Abstract. T-cell prolymphocytic leukemia (T-PLL) is a postthymic T-cell neoplasm with a characteristic morphology and heterogeneous immunophenotype. Most cases of T-PLL express membrane T-cell receptors (TCRs) of the αβ phenotype. We experienced a 30-year-old man suffering from TCRγδ T-cell leukemia with morphology compatible to T-PLL with a postthymic phenotype. He was admitted with skin eruption and pancytopenia. Peripheral blood and bone marrow were occupied with medium-sized lymphocytes, which had moderately condensed chromatin with a single nucleolus and sparse, nongranular basophilic cytoplasm. The immunophenotype was CD1a–, CD2–, CD3+, CD4–, CD5+, CD7+, CD8–, and terminal deoxynucleotidyl transferase negative. Hepatosplenomegaly was absent. He was diagnosed as having T-PLL and was treated with combination chemotherapy. Six months later the leukemic cell became chemoresistant. Although the patient showed transient improvement in response to pentostatin, he died 13xa0months after the diagnosis. To our knowledge, this is the first case of T-PLL with a TCRγδ phenotype.

Fournier's gangrene after unrelated cord blood stem cell transplantation.

Abstract. A 16-year-old boy with refractory acute myelogenous leukemia developed Fourniers gangrene as an early complication after two-antigen HLA-mismatched unrelated cord blood stem cell transplantation. On day 25 after the transplantation, he noted abrupt onset of penile swelling with miction pain. The penile inflammation rapidly extended posteriorly to involve the scrotum and perianal tissues, inferiorly to involve the thighs, and superiorly up the lower abdominal region within the next 36xa0h, and he died from sepsis on day 27. Fourniers gangrene presenting as a genitoperineal necrotizing fasciitis should be considered as a potential complication in umbilical-cord blood recipients in the cytopenic post-transplant phase.

Glanzmann thrombasthenia with acute myeloid leukemia successfully treated by bone marrow transplantation.

We report successful treatment by bone marrow transplantation (BMT) in an acute myeloid leukemia (AML) patient with Glanzmann thrombasthenia (GT). Genetic analysis revealed that a novel point mutation in exon 3 of the GPIIb gene led to abnormal splicing resulting in an amino acid substitution and an in-frame deletion of 3 amino acid residues. Expression studies suggested a rapid degradation of the uncomplexed protein within the cells. Induction therapy for AML was performed with frequent platelet transfusions because of the patient’s severe hemorrhagic manifestations. In the second remission, the patient was successfully treated by BMT from an HLA-matched unrelated donor. Platelet function returned to normal, and the GT phenotype completely disappeared. Our experience suggests that BMT is a curative therapeutic strategy for GT. Furthermore, we believe this study is the first to demonstrate that engraftment after BMT for AML can be determined by monitoring the congenital genetic defect of GT.

Risk of Neutropenic Fever and Early Infectious Complications after Autologous Peripheral Blood Stem Cell Transplantation for Malignant Diseases

Autologous peripheral blood stem cell transplantation (auto-PBSCT) has facilitated high-dose chemotherapy for the treatment of various types of malignancy, but the factors affecting the treatment outcome have not been well defined. We evaluated patients who underwent auto-PBSCT (46 patients with hematological malignancies and 39 with solid tumors) to elucidate the risks of background factors, including age, in association with infectious complications. In contrast to former reports, faster engraftment did not influence the incidence of documented infection or neutropenic fever, whereas high age (age ≥50 years old) and delayed platelet recovery (≥18 days) were demonstrated to be positively involved. The odds ratio (OR) for documented infection in elderly patients was 4.94 (95% confidence interval, 1.22-15.8). Another risk factor of infection was the HD-ICE regimen (ifosfamide, carboplatin, etoposide) given to patients with solid tumors (OR, 8.00; 95% confidence interval, 1.61-39.7). In conclusion, we found that elderly patients and patients on the HD-ICE regimen have a higher risk of infectious complications even after auto-PBSCT. Although the clinical indications for auto-PBSCT can be extended to elderly patients, thorough precautions should be taken against infectious complications during the pre-engraftment phase.

Bilateral adrenal hemorrhage in essential thrombocythemia

Abstract. A 67-year-old woman with previously untreated essential thrombocythemia developed bilateral adrenal hemorrhage. She had no known vascular risk factors including smoking, diabetes mellitus, hypertension, and hypercholesterolemia. Her platelet count was 921×109/l. She received preemptive steroid therapy to prevent the occurrence of adrenal crisis, but 5xa0weeks later the replacement therapy was discontinued because the patient fully recovered with a normal adrenocorticotropic hormone stimulation test. Thereafter, she remained well for more than 4xa0years with a platelet count ranging from 600 to 800×109/l. Although adrenal hemorrhage is very rare, it can occur as a hemorrhagic complication of essential thrombocythemia.

Megakaryoblastic leukemia cell line MOLM-16 derived from minimally differentiated acute leukemia with myeloid/NK precursor phenotype

The megakaryoblastic leukemia cell line MOLM-16 was established at relapse from the peripheral blood of a 77-year-old Japanese woman with minimally differentiated acute myeloid leukemia (AML-M0). Immunophenotyping of the fresh leukemic cells revealed a myeloid/NK precursor phenotype being positive for CD7, CD13, CD33, CD34, and CD56. In addition, megakaryocyte-associated antigens CD41 and CD61 were found to be positive. The established cell line designated MOLM-16 was proliferatively responsive to the treatment with various cytokines including EPO, GM-CSF, IL-3, PIXY-321, and TPO. MOLM-16 revealed characteristics of the megakaryocytic lineage in terms of immunophenotyping being positive for CD9, CD31, CD36, CD41, CD61, CD62P, CD63, CD110, CD151, thrombospondin, von Willebrand factor (vWf), and fibrinogen. Electron microscopic analysis showed positivity for ultrastructural platelet peroxidase in the nuclear envelope. The karyotype analysis of MOLM-16 revealed various numerical and structural abnormalities including t(6;8)(q21;q24.3), t(9;18)(q13;q21) and marker chromosomes. The extensive immunological, cytogenetic and functional characterization of MOLM-16 suggests that this cell line may represent a scientifically significant in vitro model which could facilitate the evaluation of megakaryocytic differentiation.

Multilineage involvement in hypereosinophilic syndrome terminating in granulocytic sarcoma and leukaemic transformation with trisomy 8

Summary. We report a patient with hypereosinophilic syndrome (HES), which, 8 years later, transformed into granulocytic sarcoma in the brain and, subsequently, into acute myelocytic leukaemia. Repeated chromosome analyses showed a normal karyotype, until the time of leukaemic transformation when trisomy 8 was confirmed in cells from the bone marrow and cerebrospinal fluid. The combined techniques of May–Grunwald–Giemsa staining and fluorescence in situ hybridization identified trisomy 8 not only in blasts and eosinophils but also in neutrophils and erythroblasts. Our observation suggests that HES is a multilineage myeloproliferative disorder involving precursors of at least the eosinophil, neutrophil and erythroid lineages.

Can t(8;21) oligoblastic leukemia be called a myelodysplastic syndrome?

Abstract:u2002 The new World Health Organization (WHO) classification of hematologic malignancies has incorporated t(8;21) myelodysplastic syndromes (MDS) according to the French–American–British classification into the category of acute myeloid leukemia (AML) with t(8;21)(q22;q22), while our knowledge about clinicopathological features of t(8;21) oligoblastic leukemia is still limited. We present our experience with 12 patients meeting the FAB diagnostic criteria of MDS and having t(8;21), who were compared to 43 t(8;21) AML patients. The MDS and AML patients shared most hematomorphologic, immunophenotypic, and clinical features, whereas the differences lay along myeloid maturation. The MDS patients had higher percentages of circulating neutrophils and marrow myeloid cells beyond promyelocytes than the AML patients. The incidence of Auer rods in mature neutrophils in MDS was significantly higher than that in AML, and furthermore, the neutrophils in MDS more commonly contain t(8;21) than in AML. Our findings support the rationale for the WHO classification, and future studies on large patient populations should help clarify whether the spontaneous differentiation potential could be actively associated with a hematological manifestation of t(8;21) leukemias.