Jun Taguchi

Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy

We investigated hemostatic parameters in a prospective study of 16 patients who received bone marrow transplants (BMT). We found a significant rise in the levels of fibrinogen, plasmin-α2 antiplasmin inhibitor complex, tissue-plasminogen activator·plasminogen activator inhibitor complex (t-PA·PAI), von Willebrand factor antigen, and thrombomodulin on day 14 after transplant compared with values before transplant. Protein C and thrombin-antithrombin III levels did not change significantly. No significant changes in prothrombin time ratio, activated partial thromboplastin time, or protein S were detected. Patients who had grades II–IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher level of t-PA·PAI on day 14 compared with those with grades 0–I GVHD (n = 10) (P = 0.0062). Three patients with grades II–IV GVHD developed thrombotic microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted significantly lower levels of fibrinogen (P = 0.0383), and significantly higher levels of t-PA·PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14 compared with those patients who did not develop TMA. These results suggest that prothrombotic states and endothelial damage may be caused by the conditioning regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT may be useful in surveillance for TMA because of endothelial cell injury.

Thiotepa/cyclophosphamide/TBI as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome

Summary:In all, 18 patients (30–56 years; median 49) with MDS underwent allogeneic HSCT from related (n=12) or unrelated (n=6) donors after a conditioning regimen comprising thiotepa, cyclophosphamide, and TBI. GVHD prophylaxis consisted of cyclosporine (n=15) or tacrolimus (n=3) with short-course methotrexate. Four patients had low-risk disease (refractory anemia or complete remission after chemotherapy) and 14 patients had high-risk disease (RAEB, RAEB-t, or AML). Grade II–IV acute GVHD developed in six patients and chronic GVHD in 10. With a median follow-up of 31 months, the 2-year survival probability is 75% for low-risk patients and 57% for high-risk patients. One patient died of leukemia and six of treatment-related causes. This conditioning regimen requires further study in patients with MDS.

Resolution of atopic dermatitis following allogeneic bone marrow transplantation for chronic myelogenous leukemia

Resolution of atopic dermatitis following allogeneic bone marrow transplantation for chronic myelogenous leukemia

Subcutaneous Extramedullar Hematopoiesis in a Patient with Secondary Myelofibrosis Following Polycythemia Vera

We describe the case of a 73-year-old woman with secondary myelofibrosis who developed subcutaneous extramedullar hematopoiesis. Although extramedullary hematopoiesis has been generally observed in primary myelofibrosis, in this case it was seen in myelofibrosis secondary to polycythemia vera. Histological examination of the subcutaneous nodule revealed that the lesion included cells from the myeloid and megakaryocytc series. The skin lesion almost disappeared after treatment with hydroxyurea. We report here this rare manifestation in secondary myelofibrosis including a review of literature.

Relapse of Acute Promyelocytic Leukemia After 10 Years Long-Term Remission

A 46-year-old man was admitted because of back pain and pancytopenia in May 1990. Acute promyelocytic leukemia (APL) was diagnosed according to the French– American–British classification [1]. Cytogenetic analysis on the bone marrow demonstrated abnormal karyotypes of 47,XY,+8,t(15q+;17q–). He was treated with daunorubicin (DNR), behenoyl cytosine arabinoside (BHAC), 6-mercaptopurine (6-MP), and prednisolone for induction therapy. A complete remission was achieved, and then he received three courses of consolidation therapy consisting of BHAC, DNR, and 6-MP. The complete remission continued, and he had no further therapy after March 1991. In August 2000, he was admitted to Yokohama City University Hospital, because of bleeding in the oral cavity. The peripheral blood examination revealed hemoglobin: 11.8 g/dl, white blood cell count: 3.3 £ 10/l with 66.0% promyelocyte, and platelet count: 35 £ 10 l. Cytogenetic analysis of bone marrow cells cultured for 48 and 72 h without phytohemagglutinin was analyzed by the G-banding technique. All of 20 bone marrow cells at the time of relapse had 47,XY,+8, t(15;17)(q22;q11 , 21). PML– RARa was also detected in bone marrow cells by reverse transcription polymerase chain reaction (RT-PCR). He was treated with all-trans retinoic acid (ATRA) therapy (45 mg/m/day). A complete remission was achieved again in October 2000. He received one additional course of consolidation therapy consisting of BHAC, DNR, and 6-MP. However, the PML–RARa transcript was also detected after the consolidation therapy. He was given 45 mg/m of ATRA per day for 6 months as maintenance therapy. In May 2001, minimal residual disease (MRD) was not detected by RT-PCR for PML–RARa, and he continues to be in hematologic and cytogenetic remission. Relapse of APL after long-term remission is very rare [2,3]. Inokuchi et al. reported a case of APL, which relapsed after 9.5 years remission without MRD [4]. To the best of our knowledge, relapsed case of APL after 10 years remission has not been reported until now. In this patient, although possibility of therapy related leukemia associated with treatment for primary APL cannot be excluded completely, the relapse of APL was diagnosed on the basis of cytogenetic analysis of the bone marrow cells. Divero et al. reported that APL patients in long-term remission, who are consistently RT-PCR negative for PML–RARa, are cured of their disease with eradication of residual leukemia [3]. The RT-PCR for detecting MRD was not performed in our case during remission. However,

Primary Splenic Hodgkin's Disease with Remarkable Granulomatous Reaction

A 7 I -year-old man was admitted to our hospital with low-grade fever in February 1998. Physical examination revealed some pallor. There was no lymphadenopathy. Laboratory studies were normal except for serum IgA of 859 mg/dl and soluble IL-2R of 935 U/ml. A bone marrow aspirate demonstrated slight dysplasia without atypical cells. Imaging studies, such as ultrasonography (US), computed tomography (CT). and gallium scintigraphy were present However, these studies indicated no remarkable findings and he was discharged without medication in March 1998. He was hospitalized again because of high-grade fever (38-39°C) and malaise in December 1998. The peripheral blood findings were within normal limits. The serum level of lactate dehydrogenase was elevated to 469 U L and IL-2R to 1990 U/ml, but all other blood chemistries and serological studies including antibody for virus were normal. There was no detectable peripheral lymphadenopathy. The abdominal CT scan revealed splenomegaly with a mass and a low density area in the liver. US-guided biopsy of the splenic mass was performed, but the specimen was not enough for diagnosis. Then, he underwent splenectomy for diagnosis in February 1999 (Fig 1). The histologic study of the splenic lesion demonstrated large, atypical lymphoid cells with non-caseating granulomas (Fig 2). Immunohistochemical analysis showed strong positivity in the majority of the atypical cells with CD30 antibodies.

Improvement of Quality of Life after Splenectomy in an HTLV-I Carrier with T-Cell Prolymphocytic Leukemia

A 34-year-old woman of HTLV-I carrier with T-PLL, whose quality of life improved and survival was prolonged after splenectomy, is described. The patient had marked splenomegaly, generalized lymphadenopathy and marked proliferation of abnormal lymphocytes in the peripheral blood with an irregular nucleus, deeply basophilic cytoplasm and a single prominent nucleolus, which were positive for CD2, CD3, CD5, CD7, CD4 and CD8. Although the patient had serum antibody against HTLV-I, HTLV-I proviral DNA integration was not detected. She was diagnosed as an HTLV-I carrier with T-PLL and received combination chemotherapy and 15.1 Gy splenic irradiation. However, the generalized lymphadenopathy and splenomegaly did not improve. The patient underwent splenectomy to palliate abdominal distension and hypersplenism. After the operation, her symptoms improved dramatically and within a week her hemoglobin concentration and platelet count normalized. She was discharged from hospital two weeks after the splenectomy, however 11 months later, she relapsed and despite treatment with chemotherapy and alpha-interferon, she died two months after the second admission. Autopsy findings revealed that PLL cells had invaded the bone marrow, lymph nodes, liver, lungs, kidneys, uterus, ovaries and adrenal glands.