Sakashita C

Adenovirus Is a Key Pathogen in Hemorrhagic Cystitis Associated with Bone Marrow Transplantation

Late-onset hemorrhagic cystitis (HC) is a well-known complication of bone marrow transplantation (BMT) that is mainly attributed to infection with BK virus (BKV) and adenovirus (AdV). From 1986 through 1998, 282 patients underwent BMT, and 45 of them developed HC. Urine samples tested positive for AdV in 26 patients, of which 22 showed virus type 11. Among patients who underwent allogeneic BMT, logistic regression analysis revealed acute graft-versus-host disease (grade, > or = 2) to be the most significant predictive factor for HC (P < .0001). In addition, a total of 193 urine samples regularly obtained from 26 consecutive patients who underwent allogeneic BMT were examined for BKV, JC virus (JCV), and AdV by means of polymerase chain reaction. Of patients without HC, approximately 30% of the specimens tested positive for BKV (58 samples) and JCV (55 samples), whereas 5 (3%) tested positive for AdV. Of the 3 samples obtained from patients with HC, the numbers of positive results for BKV, JCV, and AdV were 3, 1, and 1, respectively; the numbers of positive results increased to 14 of 17, 9 of 17, and 10 of 17, respectively, when we added another 14 samples obtained from 14 patients with HC (P < .0001, P = .026, and P < .0001, respectively). In conclusion, there was significant correlation between AdV and HC in the patients we studied.

Establishment of a double Philadelphia chromosome-positive acute lymphoblastic leukemia-derived cell line, TMD5: effects of cytokines and differentiation inducers on growth of the cells.

A double Philadelphia chromosome (Ph)-positive leukemia cell line with common-B cell phenotype, designated TMD5, was established from the blast cells of a patient with double Ph-positive acute lymphoblastic leukemia. TMD5 cells expressed 190 kDa BCR/ABL chimeric protein and 145 kDa ABL protein. The cells proliferated without added growth factors. Autocrine growth mechanism was not recognized. The addition of growth factors such as G-CSF, GM-CSF, IL-3, IL-6, or Stem Cell Factor did not affect the growth. Herbimycin A suppressed the growth of TMD5 cells at the low concentration that did not affect Ph-negative cells. It suppressed tyrosine phosphorylation of intracellular proteins in TMD5 cells. Dexamethasone and dibutyryl cyclic AMP also suppressed the growth. They, however, did not affect the phosphorylation significantly. Neither all-trans retinoic acid nor interferon-alpha affected the growth. TMD5 cells, characterized minutely here and rare in that they have double Ph chromosomes, will be a useful tool for the study of Ph-positive leukemia.

Two M‐components in a single cell lineage in a patient with a dual isotype secretory B‐cell tumour

We describe a case of Waldenströms macroglobulinaemia with two M‐components (IgM and IgG) with the same λ light chain. Southern blot analysis of bone marrow cells showed rearrangements of immunoglobulin heavy and λ light chain genes.

Therapy-related leukemia with Inv(16)(p13.1q22) and type D CBFB/MYH11 developing after exposure to irinotecan-containing chemoradiotherapy.

A 40-year-old woman developed therapy-related acute myeloid leukemia (t-AML) with inv(16)(p13.1q22) and a rare type D form of core-binding factor β-subunit gene-myosin heavy chain 11 gene (CBFB-MYH11) fusion transcript approximately 2.5 years after receiving chemoradiotherapy for uterine cervical cancer. t-AML with inv(16)(p13.1q22) and rare non-type A CBFB-MYH11 typically develops after exposure to a topoisomerase II inhibitor, with a short period of latency of one to five years. As the patient had no history of exposure to topoisomerase II inhibitors, among her previously used chemotherapeutics, the topoisomerase I inhibitor, irinotecan, was speculated to be the most plausible cause of t-AML in this case. The present case suggests that irinotecan may cause t-AML resembling that associated with topoisomerase II inhibitors.

Acquired Storage-Pool Disorders Occurring Late After Allogeneic Bone Marrow Transplantation: Partial Activation of Platelets in Asymptomatic Patients

Bone marrow transplantation (BMT) may be complicated by coagulation abnormalities. The present study evaluated whether platelets might be activated in patients who had undergone BMT without significant coagulopathy. The patients selected had received allogeneic BMTs a median of 39 months before the study (range, 11–124 months) and had not received cyclosporine, FK506 (tacrolimus), or other medication affecting cyclo-oxygenase for at least 3 months prior to the collection of blood samples. Furthermore, patients had platelet counts greater than 100 × 109 cells/L and normal serum creatinine levels. Twenty-five healthy volunteers acted as controls. Platelet aggregation studies and a mepacrine assay of platelets showed abnormal aggregation and decreased staining in some patients. The platelet storage-pool adenosine 5′-triphosphate (ATP) level in 15 patients after BMT was 0.45 ± 0.24 μmol per 1011 platelets, whereas the level in 18 controls was 1.03 ± 0.36 μmol per 1011 platelets (P = .00078). The total ATP levels of platelets in patients and controls were 4.33 ± 1.14 and 5.63 ± 1.51 μmol per 1011 platelets, respectively (P = .016). With the exception of 1 patient, plasma levels of thrombomodulin and von Willebrand factor were all within the normal range. The average plasma level of 11-dehydrothromboxane B2 was significantly increased in 15 patients after BMT compared with controls, 20.6 ± 8.2 and 10.3 ± 1.2 pg/mL, respectively (P = .0004). These findings suggest a long-term process of platelet activation in patients after BMT and, following the cessation of cyclosporine, development of acquired storage-pool disorder of platelets.

[Refractory primary myeloid sarcoma of the breast with MLL-AF9 rearrangement].

A 28-year-old woman presented with a right breast mass and axillary lymphadenopathy. Biopsy of the breast mass revealed myeloid sarcoma (MS) staining positive for CD4, CD13, CD33, and CD68/KP-1. Bone marrow aspiration revealed leukemic cell infiltration (9%). Leukemic cells possessed cytogenetic abnormalities of +8 and t(9;11)(p22;q23) with +22 (lymph node only), and molecular analyses confirmed the MLL-AF9 fusion gene. After induction chemotherapy and 2(nd) consolidation therapy, complete remission was maintained. However, during consolidation radiotherapy for the breast mass, the disease progressed in both the breast and bone marrow. She received re-induction therapy and proceeded to allogeneic stem cell transplantation. However, the disease relapsed in the breast soon after transplantation, and she died from disease progression. Trisomy 8 and the MLL-AF9 fusion gene have been reported in cases with MS in the breast. Trisomy 22 found additionally and exclusively in the extramedullary lesion implies extramedullary progression of MS from the medullary site of origin and may have been associated with the distinctive therapy resistance of these lesions in our case.