[Safety and efficacy of 7-day administration of azacitidine and venetoclax combination therapy (7+7 therapy)].

Acute myelogenous leukemia (AML) has a poor prognosis in patients who are ineligible for intensive chemotherapy. The combination of azacitidine and venetoclax has been shown to have high overall efficiency and remission rates, even in patients ineligible for aggressive chemotherapy. However, myelosuppression is often prolonged after treatment, and infection can also occur. Severe myelosuppression is often addressed by dose titration, but specific dose titration methods have not been clarified. We used the standard induction therapy with azacitidine plus venetoclax, and if blasts decreased to 20% or less, switched to 7+7 therapy to shorten venetoclax to 7 days starting from the next cycle. In the 19 patients we treated (median age 80 years), response rate above MLFS was 100%, CR 57.9%, CRc (CR+CRi) 78.8%, median OS 693 days, median PFS 458 days, and median OS was not reached in previously untreated patients. This indicates that 7+7 is a highly effective and well-tolerated treatment.

Copper deficiency-induced pancytopenia after taking an excessive amount of zinc formulation during maintenance hemodialysis.

Erythropoiesis-stimulating agent (ESA) has been recognized as an effective way in the treatment of anemia due to chronic kidney disease, but we sometimes see intractable hemodialysis (HD) patients. The causes of ESA-resistant anemia in HD patients include deficiency of trace elements. We report the case of an 89-year-old male who developed pancytopenia after taking an excessive amount of zinc formulation for ESA-resistant anemia during maintenance dialysis. He was prescribed zinc acetate hydrate formulation about 6 months before his presentation. He was found to have pancytopenia 1 month before his presentation, at which point he was introduced to our hospital. We suspected a copper deficiency at the first visit and stopped zinc and added copper, and his condition subsequently improved without being handicapped. Zinc antagonizes copper, so we must take care to diagnose patients ingesting zinc supplements.

Atypical chronic myeloid leukemia achieving good response with azacitidine.

The prognosis of atypical chronic myeloid leukemia (aCML) patients is poor, but some patients with a suitable donor can be treated with allogeneic hematopoietic stem cell transplantation (HSCT). However, many of these patients cannot be treated with HSCT due to their age. The effectiveness of decitabine was recently indicated in case reports; however, the effectiveness of azacitidine (AZA) has not yet been reported. We report the case of a aCML patient successfully treated with AZA. A 66-year-old man with no remarkable medical history was admitted to our hospital because of leukocytosis. We diagnosed his disease as aCML and administered hydroxyurea (HU) and AZA. After four courses of AZA, his blood cell values improved, and he no longer needed transfusions and was able to stop HU. He continued receiving AZA without any severe complications. This is the first report that AZA is effective for the treatment of aCML.

Stem cell transplantation using non-myeloablative conditioning regimen with fludarabine for hematological malignancies.

Stem cell transplantation (SCT) is a useful treatment for hematological malignancies, but it is limited to younger patients because of its high treatment-related mortality. Fludarabine (Flu), a novel anticancer agent with potent immunosuppressive activity, used as a conditioning regimen (reduced intensity transplantation; RIST), can decrease treatment-related mortality, as recently reported. However, the best drug combination and the best timing for RIST remain unknown. We herein report the SCT outcomes of 36 patients undergoing Flu treatment at our institution since December 2002 and retrospectively analyze the results. RIST conditioning with Flu was well-tolerated. No severe toxicity related conditioning regimens was observed in our patients, even though there were 10 patients with a history of autologous (n = 5) or allogeneic stem cell transplantation (n = 5). Hematological engraftment was found in 33 patients. The median times for reconstitution of WBCs, RBCs, and platelets were 16 days, 27.5 days and 34 days, respectively. Stable complete donor chimerism after SCT was present in all patients with WBC engraftment, and no patients experienced late rejection. Thirty-two patients were evaluated for acute graft versus host disease (aGVHD). Nine patients had no aGVHD. The incidence of grade I/II and III/IV aGVHD was 78% and 22%, respectively. Skin lesions were the major sites of involvement. Gut involvement was present in 9 patients. All 4 patients with grade IV GVHD had stage four hepatic GVHD. Twenty-two patients were analyzed for chronic GVHD (cGVHD). Twelve patients had no cGVHD, 6 had limited type and 4 had extended type. The overall survival (OS), relapse rate (RR), and non-relapse mortality (NRM) in all patients over 7 years were found to be 41.7%, 20.1%, and 34.6%, respectively. Induction failures were present in 5 cases of AML and 1 case of NHL. Disease progression was the primary cause of death, which occurred in 12 of 21 patients. Six patients died of grade IV GVHD (n = 2) or complicated fungal infection contracted during the GVHD treatment (n = 4). One patient died of secondary MSD, which originated from donor hematopoietic cells. Two patients died of cerebral bleeding and cardiac rapture, respectively. We found that the patients' state on SCT was the most important factor in long-term survival. The OS of standard risk and high risk patients with hematological malignancies were 75% and 30.3%. We concluded that stem cell transplantation using a non-myeloablative conditioning regimen with Flu was a useful therapeutic approach for patients with hematological malignancies.

[Epstein-Barr virus-related B-cell lymphoma of the skin which developed early after cord blood transplantation for angioimmunoblastic T-cell lymphoma].

We report here a rare case of EBV-related post-transplantation lymphoproliferative disorder (PTLD) localized to the skin. The patient was a 64-year-old man diagnosed with angioimmunoblastic T cell lymphoma (AITL). He underwent cord blood transplantation with a reduced intensity conditioning regimen during partial remission after chemotherapy. On day 70 after transplantation, subcutaneous tumors developed near the left scapula and in the left upper arm. Pathological examination of the skin tumor revealed that this tumor was composed of diffuse large centroblast-like cells, the majority of which were CD20 positive, CD 79a positive, CD30 positive and Epstein-Barr virus (EBV) latency-associated RNA (EBER) positive, and EBV-DNA was also detected in tumor cells. At that time, real-time polymerase chain reaction documented no evidence of the EBV genome in his blood. Chimerism analysis revealed that the tumor cells were derived from donor cells, which led to the diagnosis of EBV-related PTLD. For treatment, in addition to decreasing the dose of tacrolimus, we administered rituximab and local irradiation to skin lesions, which led to disappearance of the tumors followed by continued complete remission.

Analysis of triglyceride value in the diagnosis and treatment response of secondary hemophagocytic syndrome.

BACKGROUND/AIMS: Secondary hemophagocytic syndrome (hemophagocytic lymphohistiocytosis, HLH) follows viral infection, malignant disorders, and autoimmune disease. Criteria for HLH diagnosis, which were proposed in 2004, include hypertriglyceridemia. However, some studies reported the absence of hypertriglyceridemia in patients with secondary HLH, differing from those with primary HLH. SUBJECTS AND METHODS: In this study, we investigated the presence or absence of hypertriglyceridemia in 28 patients who were diagnosed with secondary HLH between 1997 and 2007 retrospectively. There were no patients undergoing treatment for those with a history of hyperlipidemia. RESULTS: The subjects consisted of 14 patients with lymphoma-associated HLH, 11 with virus-associated HLH, 2 with autoimmune disease-associated HLH, and 1 with post transplantation HLH. In 19 patients (68%), hypertriglyceridemia was noted on diagnosis or during the disease period (mean: 242 mg/dL). Furthermore, the triglyceride (TG) level decreased with the treatment-related amelioration of HLH (mean level before and after treatment: 297 and 136 mg/dL, respectively, p=0.0001). CONCLUSION: These results suggest that the TG level is useful for diagnosing HLH and evaluating the treatment response. TG measurement is simple and inexpensive; therefore, this parameter can be determined several times to evaluate the treatment response.

Umbilical-cord blood cell transplantation conditioned with a reduced intensity-regimen is a practical salvage therapy for severe aplastic anemia refractory to immunosuppressive therapy with antithymocyte globulin/ciclosporin.

Immunosuppressive therapy and stem cell transplantation from an HLA-identical donor are the major effective treatments for severe aplastic anemia. However, treatments still need to be developed for patients who do not have a HLA-identical donor and have not shown a clinical response to immunosuppressive therapy. We herein report on 2 patients in whom this problem could be overcome by transplantation of HLA-mismatched umbilical cord blood from unrelated donors. Two Japanese patients with severe aplastic anemia underwent conditioning with fludarabine, cyclophosphamide, and low-dose total-body irradiation and then received transplants of umbilical cord blood. Engraftment of the three lineages occurred without problems. We conclude that umbilical cord blood transplantation with a reduced-intensity conditioning regimen of fludarabine, cyclophosphamide, and total-body irradiation for patients with aplastic anemia is a practical treatment and may be an attractive alternative for patients who does not have an HLA-identical donor and have shown no clinical response to immunosuppressive therapy.

[Double balloon endoscopy as a useful tool for the diagnosis and treatment of four cases of primary small intestinal lymphoma].

Primary small intestinal lymphoma (PSIL) is a relatively rare form of non-Hodgkin lymphoma, often complicated by bleeding, obstruction, or perforation of the intestine during the clinical course. The initial diagnosis and management of these complications are often difficult in PSIL, because the small intestine is usually inaccessible in routine endoscopy. Recently, total enteroscopy with a double-balloon method, called double balloon endoscopy (DBE), has been developed for the diagnosis and treatment of small intestinal disorders. We report herein on 4 cases of PSIL (2 diffuse large B-cell lymphomas and 2 follicular lymphomas [FLs]). In these cases, DBE was useful in the diagnosis, decision to perform surgery after assessment of bleeding lesion, and treatment of the intestinal stenosis using enteroscopic balloon dilatation. Combination chemotherapy consisting of anthracycline, cyclophosphamide, vincristine, and prednisolone with rituximab was administered in 3 cases, and all achieved complete remission. One patient with FL of the duodenum was treated with rituximab alone, but with little effect. We conclude that DBE is useful in the management of PSIL. More PSIL cases must be analyzed to establish the optimal management of patients with this form of lymphoma.