Fuminori Sano

Philadelphia chromosome-positive acute myeloid leukemia (Ph + AML) treated with imatinib mesylate (IM): A report with IM plasma concentration and bcr-abl transcripts

We studied the efficacy and pharmacokinetics of imatinib mesylate (IM) and bcr-abl expression in a Philadelphia chromosome-positive acute myeloid leukemia (Ph + AML) patient, a rare disease with a poor prognosis. Although sufficient IM trough concentrations were maintained, bcr-abl transcripts revealed only one-log reduction with IM monotherapy, suggesting a resistance against IM, and this patient required additional chemotherapy. Despite the resistance against IM at induction therapy, the patient has been in complete molecular response for more than 6 months with IM maintenance monotherapy. Our experience suggests that IM might have a positive role in consolidation and/or maintenance therapy in remission Ph + AML patients.

Successful treatment of meningoencephalitis caused by methicillin-resistant Staphylococcus aureus with intravenous linezolid in an allogeneic cord blood stem cell transplant recipient

Methicillin-resistant Staphylococcus aureus (MRSA) is an infectious pathogen that commonly occurs after stem cell transplantation. We report a case of meningoencephalitis with multiple abscess formation caused by MRSA, which occurred in a 62-y-old female soon after allogeneic cord blood transplantation, and which was successfully treated by the administration of intravenous linezolid.

Philadelphia chromosome-positive acute lymphoblastic leukemia with extramedullary and meningeal relapse after allogeneic hematopoietic stem cell transplantation that was successfully treated with dasatinib

Central nervous system (CNS) relapse is a critical issue while treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). A 58-year-old woman with Ph-positive ALL who relapsed after bone marrow transplantation for meningeal leukemia was treated with high-dose methotrexate, which resulted in remission. She underwent allogeneic cord blood transplantation followed by reduced intensity conditioning chemotherapy with imatinib; however, she experienced CNS relapse and developed an extramedullary mass on the right side of the temporal region. We treated 40 mg of dasatinib once daily, which had to be temporarily discontinued because she developed grade 2 pleural effusion and grade 2 hematemesis. After reinitiation of dasatinib, the extramedullary mass disappeared and meningeal leukemia ameliorated almost immediately. With 40 mg dasatinib administered once daily, its trough level and cerebrospinal fluid (CSF) concentration were 32 ng/mL and below the sensitivity threshold of 1 ng/mL, respectively. Treatment was continued, and the patient remained in complete remission until she died of pneumonia 7 years after the initial diagnosis of ALL. Dasatinib can be an effective treatment for Ph-positive ALL with CNS relapse. Although the concentration in the CSF seems low, it may be sufficient to exert anti-leukemic effects in the human CNS.

Small cell variant of anaplastic large cell lymphoma diagnosed by a novel chromosomal abnormality t(2;5;3)(p23;q35;p21) of bone marrow cells

Because of the rarity and the morphological variations, small cell variant of anaplastic large cell lymphoma (ALCL) represents a diagnostic challenge. Herein is reported a case of leukemic type of small cell variant of ALCL, in which the diagnosis was established by a cytogenetic analysis. The patient was a 23‐year‐old woman who presented with fever and leukocytosis with circulatory atypical lymphoid cells. The initial differential diagnosis on bone marrow trephine biopsy sections included viral infection and peripheral T‐cell lymphoma unspecified. But a cytogenetic study on bone marrow cells indicated a novel complex translocation, t(2;5;3)(p23;q35;p21), which led to confirmation of anaplastic lymphoma kinase (ALK)‐positive pleomorphic small to medium‐sized cells scattered in bone marrow cells, on immunohistochemistry. ALK was distributed in both nuclear and cytoplasmic regions of neoplastic cells. The patient achieved complete remission after four courses of combination chemotherapy, and received autologous peripheral stem cell transplantation (auto‐PBSCT) after two additional courses of combination chemotherapy, but relapsed 2 months after auto‐PBSCT in the bilateral lung. Allogeneic stem cell transplantation led to a second remission. This case demonstrates the diagnostic importance of cytogenetic study for malignant lymphoma involving bone marrow.

Transformation from follicular lymphoma to high-grade B-cell lymphoma/leukemia with additional t(2;8)(p12;q24), with inverse expressions of c-MYC and BCL-2, and light-chain switch

Transformation from follicular lymphoma (FL) to high‐grade B‐cell lymphoma/leukemia (BLL) has been reported in patients with additional translocations involving the c‐MYC gene. The previously reported cases were related to t(8;14) and t(8;22) but not to t(2;8). Herein is reported an FL that terminated in BLL following additional t(2;8). In accordance with previous reports, increased expression of c‐MYC was observed in the present case but, interestingly, BCL‐2 expression was inversely decreased after the transformation. In addition, the cell‐surface immunoglobulin light‐chain of lymphoma cells was initially κ type and was then gradually replaced with the λ type after transformation. Downregulation of BCL‐2 and light‐chain switch have rarely been reported in previous cases of FL transformation involving c‐MYC, suggesting that additional t(2;8) translocation may play a role in these events.

Amyloid-associated amyloidosis in a HCV carrier with non-Hodgkin's lymphoma who had been treated with autologous stem cell transplantation and rituximab

Amyloid-associated (AA) protein is a unique type of non-immunoglobulin protein. AA fibrils (8500 Da) are derived from a larger precursor (12,000 Da) in the serum called SAA (serum amyloid-associated) protein, which is synthesized in the liver and whose production is enhanced by interleukin-6 (IL-6) [1]. AA-type systemic amyloidosis has been referred to as secondary amyloidosis because it is secondary to an associated inflammatory condition [2]. AA-type systemic amyloidosis is extremely rare in patients with non-Hodgkin’s lymphoma (NHL). Until now, only two cases of systemic AA-type amyloidosis have been reported [3,4] among NHL patients, and other than these, it has been reported in one patient with NHL, who had a localized amyloid presenting as an epigastric abdominal mass [5]. Here, we report an autopsied case of diffuse large B-cell type lymphoma with systemic AA-type amyloidosis. A 45-year-old man was admitted to our hospital in May 2004 due to continuing high fever. Because of liver mass (76 8 cm) and abnormal levels of LDH (4500 IU/mL) and soluble IL-2 receptor (13,900 U/mL), a liver biopsy was performed. The findings obtained revealed an aggregate of large lymphoid cells with irregular nucleus and prominent nuclei as well as frequent mitotic figures. Immunoperoxidase staining using antigen-retrieval methods showed that the lymphoma cells were positive for CD20 and, CD79a but negative for CD3, CD10, CD 5, and CD 30. EBER-1 in situ hybridization was also performed using a DNA-probe, but no signal was observed. A bone marrow biopsy revealed that identical lymphoma cells were present in the bone marrow. Therefore, the patient was diagnosed to have diffuse large B-cell lymphoma (stage IV B, IPI: high-intermediate risk). A routine serological study on admission revealed that the patient was negative for the hepatitis C virus (HCV). Lymphoma was treated with a combination chemotherapy consisting of cyclophosphamide, doxorubicin, prednisolone, cytarabine, bleomycin, methotrexate, and etoposide (ProMACE-CytaBOM) with rituximab. Intrathecal prophylaxis for lymphoma was not performed until relapse. Complete remission was obtained following another cycle of this combination. After four additional cycles of this chemotherapy, the patient received a high dose chemotherapy consisting of carboplatin, ranimustine, etoposide, cyclophosphamide, and rituximab, followed by support care using autologous peripheral blood stem cells in April 2005, which was conducted because of his insufficient response to induction chemotherapy and high IPI scores. In July 2005, the patient presented with progressing aphasia, right-sided paralysis, and disorientation. Cranial computer-assisted tomography clearly showed a lesioned area in the left cerebral cortex. Biopsy was not performed because of the high risk estimated by the neurosurgeon. The tumor size