SF3B1 and IGHV gene mutation status predict poor prognosis in Japanese CLL patients.

The incidence of chronic lymphocytic leukemia (CLL) is low in Japan. The clinical course ranges from very indolent to rapidly progressive. Recently, several reports have indicated that mutation of the splicing factor 3b, subunit 1 (SF3B1) gene in CLL is predictive of a poor prognosis. Here, we investigated the SF3B1 mutational status of Japanese CLL patients and clarified the association between SF3B1 mutational status and prognostic factors. One hundred and two patients that were referred to our institutions between 1999 and 2013 were enrolled. Mutation analysis of SF3B1 (n = 87) and of the immunoglobulin heavy chain gene (IGHV) (n = 102) was performed at diagnosis. FISH analysis of del(11)(q22) was performed for 17 patients. Seven patients have SF3B1 mutation (8.0 %: K700E, 5/7; G742D, 1/7 and Y623C, 1/7). The median survival times for patients with mutated and non-mutated SF3B1 were 53 and 130 months, respectively. Overall survival of the mutated SF3B1 group was significantly lower than that of the non-mutated group (p = 0.0187). No relationship was observed between IGHV mutational status and SF3B1 mutation. There was no patient with SF3B1 mutation in the IGHV1-69 population (0/2). In conclusion, mutation of SF3B1 at diagnosis in Japanese CLL patients is predictive of a poor prognosis.

Clinical experience of bendamustine for adult Langerhans cell sarcoma.

A 40-year-old man was diagnosed with Langerhans cell histiocytosis (LCH) in October 2010. His LCH was refractory to conventional chemotherapy, and thus worsened to Langerhans cell sarcoma (LCS) in May 2011. Although we repeated combination chemotherapies, new infiltration of the liver and bone marrow, as well as primary lesions of the bone, lymph nodes, and skin, appeared. These intensive chemotherapies caused candida liver abscesses, invasive aspergillosis, disseminated varicella zoster virus infection and bacterial sepsis. We administered bendamustine for chemotherapy, which resulted in a partial response (PR) with no severe adverse events. Because of pancytopenia caused by secondary myelodysplastic syndrome, we stopped the bendamustine chemotherapy after two courses. PR was maintained for 4 months. We plan to perform allogeneic hematopoietic stem cell transplantation from a sibling donor after a conditioning regimen. Optimal therapy for adult LCH, which is a rare and treatment-resistant disease, has yet to be established. Bendamustine is a potential chemotherapeutic agent for standard treatment of LCS.

Prognostic importance of the soluble form of IL-2 receptorα (sIL-2Rα) and its relationship with surface expression of IL-2Rα (CD25) of lymphoma cells in diffuse large B-cell lymphoma treated with CHOP-like regimen with or without rituximab: a retrospective analysis of 338 cases.

We evaluated the prognostic significance of the serum level of the soluble form of interleukin-2 receptorα (sIL-2Rα) and investigated its association with CD25 expression on tumor cells in diffuse large B-cell lymphoma (DLBCL). Three hundred and thirty-eight adult patients with newly diagnosed DLBCL were eligible for this retrospective study. 32.2% of patients were treated with CHOP-like regimen and 67.8% with R-CHOP-like regimen. CD25 expression on the surface of tumor cells was evaluated in 143 cases and its relationship with sIL-2Rα level was also investigated. Both overall survival (OS) and progression-free survival (PFS) were poorer in patients with higher sIL-2Rα, in both R-CHOP and CHOP groups. sIL-2Rα > 1,000 U/mL and performance status (PS) ≥ 2 were independently associated with poorer OS, and sIL-2Rα > 1,000 U/mL, age > 60 years, and ≥ 2 extranodal sites were independently associated with poorer PFS in the R-CHOP group. The sIL-2Rα level was higher in the CD25-positive group than in the CD25-negative group in stage 3 or 4 disease (p = 0.010). Multiple linear regression analysis showed CD25 expression to be independently correlated with sIL-2Rα levels. High sIL-2Rα is an important risk factor for survival in DLBCL treated with not only CHOP-like, but also R-CHOP-like regimens, regardless of the tumor's expression of CD25.

[Retrospective survey on the clinical features of non-Hodgkin lymphomas in Gunma Prefecture, Japan].

We retrospectively investigated pathological types, clinical backgrounds, treatments and prognoses in 726 adult patients with newly diagnosed malignant lymphoma in Gunma Prefecture. They consisted of 679 patients with non-Hodgkin lymphoma (B-cell type, 603; T- and NK-cell type, 76) of which 376 patients had diffuse large B-cell lymphoma (DLBCL) and 47 patients with Hodgkin lymphoma. When comparing the prognosis of DLBCL between patients receiving rituximab (R-CHOP group; n=212) and not using rituximab (CHOP group; n=126), both 3-year overall survival (73.5% vs 61.7%, p=0.010) and 3-year progression-free survival (65.1% vs 45.8%, p<0.001) were statistically better in the R-CHOP group compared to the CHOP group. Our results suggest that more than half of patients were DLBCL and the rituximab-containing regimen results in an improved prognosis for DLBCL patients.

Enteric duplication cyst of the pancreas with duplicated pancreatic duct.

Enteric duplication cyst is one of the rarest forms of cystic lesion of the pancreas. We report a unique case of an enteric duplication cyst of the pancreas that was communicating with a duplicated pancreatic duct. A 7-year-old girl with severe acute abdominal pain was found to have a large cyst that was smoothly communicating with the dilated pancreatic duct in the pancreatic tail. Analysis of cyst fluid showed elevated levels of amylase, carcinoembryonic antigen (CEA) and CA 19-9, and no epithelial cells. Intraoperative cyst pancreatography revealed that the pancreatic duct was duplicated in the tail: 1 duct was communicating with the cyst, and the other was dilated within the pancreatic tail. The patient underwent spleen-preserving distal pancreatectomy and complete cyst excision without complication. Because preoperative diagnosis of duplication cyst of the pancreas is difficult, this condition should be considered during differential diagnosis of atypical cystic lesions of the pancreas. Complete excision is desirable for the management of duplication cyst of the pancreas.

Type I biliary atresia without extrahepatic biliary cyst.

Currently, magnetic resonance cholangiography (MRC) is used for the differentiation of biliary atresia (BA) from other causes of infantile cholestasis. The authors present a case of type I BA without an extrahepatic biliary cyst in a 2-month-old girl. MRC clearly visualized the patency of the gallbladder, cystic duct, and hepatic ducts with disappearance of the common bile duct. Intraoperative cholangiography demonstrated a cloudy appearance of the intrahepatic bile ducts, confirming the diagnosis of type I BA. We believe that this is the first reported case of type I BA without an extrahepatic biliary cyst diagnosed by MRC.

Prolonged sevoflurane inhalation therapy for status asthmaticus in an infant.

A 3-month-old boy with retractive breathing from his birth was scheduled for a rigid bronchoscopic examination. Anesthesia was induced and maintained with sevoflurane. The examination revealed a slight laryngomalacia which was not compatible with his severe symptom. During the procedure, no respiratory deterioration occurred. He was once extubated in the operating room, however, developed severe desaturation immediately. He was reintubated at the scene and returned to the ward being mechanically ventilated and sedated. The next day, his respiratory condition worsened gradually. Conventional drugs including theophylline, corticosteroid and beta adrenergic agonist did not improve his deleterious condition. He became bradycardic and was on the verge of circulatory collapse as his lungs were unable to ventilate. Then, we commenced inhalation of sevoflurane using a standard anesthesia machine, which relieved him from ventilatory crisis. Although there were some difficulties in using anesthesia machine in the ICU, we could successfully manage mechanical ventilation. After the beginning of sevoflurane inhalation, his condition improved gradually. Discontinuation of sevoflurane was difficult and it took 94 h to wean from sevoflurane inhalation. Despite long duration of inhalation, no adverse effects of sevoflurane were observed except transient mild increase in liver transaminase. There have been very few reports on application of sevoflurane inhalation for such a long period in infants with bronchospasm. Moreover, measured serum fluoride concentration (24.2 micromol x l(-1)) during inhalation was well below harmful level. Sevoflurane inhalation is worth attempting and safe to treat life-threatening bronchospasm even in infants.

[Splenic marginal zone B-cell lymphoma with bilateral renal invasion after splenectomy].

A 61-year-old woman presented with hepatosplenomegaly, systemic lymphadenopathy, anemia, and thrombocytopenia. Peripheral blood and bone marrow examination showed atypical lymphoid cells with villi. Immunophenotyping of these cells was CD19+CD20+CD5-CD10-CD23-, and light chain restriction (kappa) was positive. To confirm the diagnosis histologically, we performed a splenectomy and diagnosed the patient's disease as splenic marginal zone lymphoma (SMZL). She rapidly recovered normal hematological parameters and gallium-67 citrate scan showed no increased uptake. Two months after the splenectomy, however, she was readmitted with findings of 15% blasts in the peripheral blood and massive infiltration of the bone marrow by large blastoid cells. Laboratory evaluations were positive for monoclonal IgM-kappa protein. Under acute renal dysfunction, we performed a CT scan that showed bilateral enlargement of the kidneys with features suggestive of an infiltrative process besides systemic lymph node enlargement. A kidney biopsy established the diagnosis of lymphoma with renal infiltration. SMZL is characterized by an indolent clinical course, and no previous report has described SMZL with bilateral renal invasion. Complete remission was obtained after 3 cycles of chemothreapy (R-CHOP). She is undergoing 3 more courses and remains in remission 6 months after the rapid progress of her illness.

[Chronic eosinophilic leukemia with symptoms resembling Budd-Chiari syndrome due to liver infiltration].

A 68-year-old woman was admitted to our hospital with severe ascites, hepatomegaly and hypereosinophilia. We initially suspected Budd-Chiari Syndrome (BCS), but that was ruled out after confirming the presence of no obstruction in the major veins. A molecular biologic examination proved the clonality of the eosinophils and she was therefore diagnosed as having chronic eosinophilic leukemia (CEL). The pathologic findings of a liver biopsy showed dilation of the sinusoids with infiltration of eosinophils, portal eosinophilic infiltrations with fibrosis, and biliary damage. These findings thus suggested infiltration of the liver by the CEL. A relationship between myeloproliferative disorders and BCS has been commonly reported, however there have so far been very few reports which describe the pathology of CEL liver infiltrates. As a result, the present case in which CEL occurred while demonstrating symptoms and findings similar to BCS is therefore considered to be extremely rare. Further accumulation of such cases should therefore be carried out in the future.

[Treatment outcome of myelodysplastic syndrome patients younger than 60 years old].

We evaluated the clinical outcome of 92 patients younger than 60 years who were treated between January 1987 and May 2003. Low, Int-1, Int-2 and High risk groups categorized by IPSS consisted of 7, 34, 24 and 27 patients, respectively. There was no significant difference in the overall survival between 30 patients who received allogeneic stem cell transplantation and 62 patients who did not. Allogeneic stem cell transplantation provided significantly better outcomes in the Int-2 and the High risk groups. Risk factors for overall survival were age and disease status at transplantation. Acute and chronic GVHD did not influence the relapse free survival rate. Allogeneic stem cell transplantation is a curative therapy for MDS. It is necessary to reduce transplantation related death and to perform stem cell transplantation as soon as possible for patients with Int-2 or High risk of IPSS.

Combination chemotherapy of ranimustine, doxorubicine, and dexamethasone for relapsing multiple myeloma--a pilot study.

Twenty patients with relapsing myeloma were treated with combination chemotherapy of ranimustine, doxorubicine, and dexamethasone (RAD) between July 1996 and March 2000. Of the 19 evaluable patients, 5 (26.3%) achieved partial response after the first round of RAD therapy and 10 (52.6%) achieved partial response after the second round of RAD therapy. Of 10 evaluable patients who had previously received high-dose dexamethasone therapy including VAD therapy, 2 (20%) achieved partial response after the first round of RAD therapy and 3 (30%) achieved partial response after the second round of RAD therapy. The median survival was 10.5 months and the progression-free survival was 9.3 months. Patients who responded to RAD therapy had a survival rate at 43 months of 59.3%. Toxicity and adverse events during RAD therapy were tolerable. This pilot study demonstrated that RAD therapy is useful for the treatment o frefractory myeloma.