Lack of Grafted Liver Rejuvenation in Adult-to-Pediatric Liver Transplantation

Background  

A grafted donor liver should grow and survive under the different conditions presented by a liver transplantation recipient. It has remained unclear, however, whether the age of a grafted liver can be modulated by recipient factors.     

Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes

Among acquired stem cell disorders, pathological links between myelodysplastic syndromes (MDS) and aplastic anaemia (AA), and paroxysmal nocturnal haemoglobinuria (PNH) and AA, have been often described, whereas the relationship between MDS and PNH is still unclear. We analysed blood cells of patients with MDS to determine the incidence of the PNH clone, and analysed the PIG-A gene to find mutations characteristic of the PNH clone in MDS. In four (10%) of 40 patients with MDS, flow cytometry showed affected erythrocytes and granulocytes negative for decay-accelerating factor (DAF) and CD59. The population of affected erythrocytes was smaller in MDS patients with PNH clone (MDS/PNH) than in patients with de novo PNH, and haemolysis was milder in the MDS/PNH patients. PIG-A mutations were found in granulocytes of all patients with MDS/PNH. In type and site, the PIG-A mutations were heterogenous, similar to that observed in de novo PNH; i.e. no mutation specific to MDS/PNH was identified. Of note, three of four patients with MDS/PNH each had two PNH clones with different PIG-A mutations, suggesting that PIG-A is mutable in patients with MDS/PNH. In a MDS/PNH patient with trisomy 8, FISH detected a distinct karyotype in a portion of granulocytes with PNH phenotype, indicating that PNH and MDS partly shared affected cells. Thus, MDS predisposes to PNH by creating conditions favourable to the genesis of PNH clone. Considering the increasing prevalence and incidence of MDS, these disorders could be useful for investigating the mechanism by which PIG-A mutation is induced.     

Successful treatment of a chronic-phase T-315I-mutated chronic myelogenous leukemia patient with a combination of imatinib and interferon-alfa

The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (CCyR) was achieved 12 months later. However, after 18 months, a loss of CCyR was observed and a molecular study at 24 months revealed a T315I mutation of the BCR-ABL gene. At 30 months, imatinib/interferon-alfa (IFNα) combination therapy was initiated in an effort to overcome the resistance. Thirty months later, he re-achieved CCyR, and the T315I BCR-ABL mutation disappeared at 51 months. To our knowledge, this is the first case report showing the effectiveness of imatinib/IFNα combination therapy for CML patients bearing the T315I BCR-ABL mutation.     

Survey on examinations for diagnosis of bone marrow failure in Japan: a report from the Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes

Using a registration sheet of a prospective registration system for aplastic anemia (AA)/myelodysplastic syndromes (MDS), by the National Research Group on Idiopathic Bone Marrow Failure Syndromes, Japan, we carried out a survey on examinations for diagnosis of bone marrow failure. Bone marrow trephine biopsy was performed in 66 of 105 cases (63%) [Original diagnosis: AA 51 cases (80%), MDS 12 (32%), undiagnosable 3 (75%)]. Bone marrow aspiration was performed in all cases, and aspiration was performed at least twice in 36 cases (34%). The first-line anatomic site for bone marrow aspiration was the posterior iliac crest (62%). Cytogenetic examination was performed in 93%. The concordance rate between the original and the central review diagnosis was 93% among the studied cases: AA, Idiopathic cytopenia of undetermined significance (ICUS) and MDS in total. Flow cytometry analysis to detect paroxysmal nocturnal hemoglobinuria (PNH)-type blood cells was performed in 32%.     

Deoxycoformycin-containing combination chemotherapy for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study (JCOG9109)

Aggressive adult T-cell leukemia-lymphoma (ATL) generally has a very poor prognosis. Deoxycoformycin (DCF, pentostatin), an inhibitor of adenosine deaminase, has shown promising therapeutic efficacy for ATL. To develop a new effective therapy against aggressive ATL, we carried out a multicenter phase II study of DCF-containing combination chemotherapy. Sixty-two previously untreated patients with ATL (34, 21, and 7 patients with diseases of the acute, lymphoma, and unfavorable chronic types, respectively) were enrolled, but 2 were ineligible because they were judged to be favorable chronic types. A regimen of 1 mg/m2 vincristine intravenously on days 1 and 8, 40 mg/m2 doxorubicin intravenously on day 1, 100 mg/m2 etoposide intravenously on days 1 through 3, 40 mg/m2 prednisolone orally on days 1 and 2, and 5 mg/m2 DCF intravenously on days 8, 15, and 22 was administered every 28 days for 10 cycles unless disease progression or toxic complications occurred. Fifty-two percent of 60 eligible patients responded (95% confidence interval [CI], 38%-65%), with 17 patients (28%) achieving a complete response (CR) (95% CI, 17%-41%) and 14 achieving a partial response. The CR rate was inferior to those of both the previous Japan Clinical Oncology Group (JCOG) study (JCOG8701, 43%), a 9-drug combination chemotherapy of the second generation, and the subsequent JCOG9303 study (35%), a granulocyte colony-stimulating factor-supported, dose-intensified, 9-drug regimen. The median survival time of the 60 eligible patients in JCOG9109 was 7.4 months, and the estimated 2-year survival rate was 15.5%; these results were identical with those of JCOG8701 but inferior to those of JCOG9303. Grade 4 neutropenia and infection of grade 3 or greater were frequent (67% and 22%, respectively), and treatment-related death was observed in 4 patients (7%), septicemia in 2, and cytomegalovirus pneumonia in 2. We conclude that DCF-containing combination chemotherapy is not a promising regimen against aggressive ATL.     

Th1, Th2, and activated T-cell marker and clinical prognosis in peripheral T-cell lymphoma,unspecified: comparison with AILD,ALCL, lymphoblastic lymphoma,and ATLL

A new World Health Organization classification was recently proposed. However, classification of peripheral T-cell lymphomas remains to be clarified. Particularly, unspecified type was considered as a heterogeneous category. Here we studied the expressions of chemokine receptors, Th1-associated CXCR3 and CCR5 and Th2-associated marker ST2(L), and activated T-cell receptor OX40/CD134 in 185 patients with nodal T-cell lymphoma, and evaluated the relationship to prognosis. Their expression patterns correlated with the specific subtype of nodal T-cell lymphoma, such as angioimmunoblastic T-cell lymphoma (AILD), anaplastic large cell lymphoma (ALCL), and in peripheral T-cell lymphoma (PTCL), unspecified. In AILD, almost all cases were immunoreactive for OX40/CD134 (96%) and for CXCR3 (89%). In ALCL, all cases were immunonegative for OX40/CD134, and only a few cases (24%) were immunoreactive for CXCR3, whereas almost all cases (94%) were positive for ST2(L). Cases of PTCL, unspecified, were divided into 2 groups; group 1 (cases positive for either ST2(L), CCR5, or CXCR3) tended to show favorable prognosis compared with group 2 (cases negative for ST2(L), CCR5, and CXCR3). Our results indicate that further subtyping of PTCL, unspecified, into groups 1 and 2 could be significant for evaluating prognosis and understanding the functional role of these tumors.     

Sialylated Lewis x as a tumor-associated antigen in stomach cancer

Sialylated Lewis (S-Lex) has been studied histologically and serologically in stomach cancer by the CSLEX1 monoclonal antibody. S-Lex was expressed in 73.9% of 46 stomach cancer tissues, 29.4% of metaplastic parts adjacent to cancer, and none of six gastric ulcer tissues including metaplasia. Serologically positive percentages were as follows: 26.0% of 100 stomach cancers, 0.9% of 322 benign diseases, and 0.7% of 280 healthy donors in the sera, as well as 72.4% of 29 ascites of stomach cancers and 5.3% of 17 effusions of benign diseases. These findings demonstrate that S-Lex possesses a potential usefulness as a tumor marker in stomach cancer.