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A 66-year-old man with fever was diagnosed with B-cell acute lymphoblastic leukemia. He failed to achieve complete remission after initial hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) therapy and was referred to our hospital to undergo allogeneic stem cell transplantation. Bone marrow aspiration showed 97.5% lymphoblasts positive for CD19. Blood tests revealed the presence of broad antihuman leukocyte antigen (HLA) antibodies. After blinatumomab therapy, bone marrow aspiration showed 19.6% blasts. Furthermore, after additional mini-mitoxantrone, etoposide, and cytarabine (mini MEC) therapy, the patient achieved complete remission. Interestingly, after blinatumomab therapy, the blood tests revealed that the titers of anti-HLA antibodies had decreased, and cord blood transplantation was performed in complete remission. This case report revealed that chemotherapy including blinatumomab, which targets CD19-positive cells, has the potential to decrease antibody-producing cells, thus leading to a dramatic reduction of anti-HLA antibodies.

A 46-year-old female patient underwent a cord blood transplantation (conditioning regimen: fludarabine/busulfan4/melphalan80; graft-versus-host disease (GVHD) prophylaxis: tacrolimus + mycophenolate mofetil) for acute myeloid leukemia (AML) with her 1st hematological complete response to induction therapy (idarubicin 3 days+cytarabine 7 days). She lost her consciousness due to human herpesvirus 6 (HHV-6) encephalitis on day 31, and therefore, we increased the foscarnet dosage (from 120 mg/kg to 180 mg/kg). Her consciousness level improved after treatment. However, 8 hours of sudden hypothermia occurred with hyperhidrosis, hypertension, and subsequent hyperglycemia on day 34. Her condition did not improve even after administration of anticonvulsant, steroid pulse, or intravenous immunoglobulin. A total of 75 attacks were observed until she was discharged on day 471. She has not shown chronic GVHD or relapsed AML since then. However, HHV-6 caused prolonged damage to her hypothalamus as observed through magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) using 99m Tc ethyl cysteinate dimer even when the virus was not detected from her cerebrospinal fluid. This damage can be responsible for the hypothermia attacks. This is the first case report of prolonged series of hypothermia attacks for over a year as a sequela of HHV-6 encephalitis after a cord blood transplantation for AML.

Although all-trans retinoic acids (ATRA) are most commonly used as agents in acute promyelocytic leukemia (APL), there are few reports on the administration of ATRAs to patients with liver insufficiency. We report two cases of APL; a 57-year-old man with APL complicated by liver cirrhosis (Child-Pugh class B) and hepatocellular carcinoma who is receiving transcatheter arterial chemoembolization (TACE) and a 50-year-old man with APL complicated by liver cirrhosis (Child-Pugh class B) who is being prepared for receiving a living-donor liver transplantation. Both patients were successfully treated with a normal dosage of ATRA alone during remission-induction therapy. Because the total bilirubin and hepatic transaminases in the two cases were almost at normal levels; the patients received three courses of ATRAs plus a 42%-70% dose of anthracyclines as a consolidation therapy. At 1 year after receiving intermittent ATRA therapy, the patients are maintaining molecular remission. These cases suggest that the administration of ATRA and modifications of doses of chemotherapeutic agents are applicable to APL patients with liver dysfunction.

To investigate the effectiveness and safety of GVHD prophylaxis using FK506 alone as a continuous infusion, 104 patients who underwent reduced-intensity cord blood transplantation were retrospectively reviewed. The respective incidence of acute GVHD was 25 grade 1(24. 1%), 19 grade2(18. 3%), 15 grade3(14. 4%), and 4 grade4(3. 8%), which are comparable to that in the literature. The incidences of grade 2 and greater acute GVHD were 32 out of 69(46. 4%)for those whose wholeblood concentration of FK506 werele ss than 13 ng/mL, whereas 6 out of 35(17. 1%)for those FK5 06 were greater than 13 ng/mL. The differenceies between above and below 13 ng/mL were statistically significant(p=0. 008). There were 19 cases(18. 3%)of renal dysfunction, although none required hemodialysis. There were only 4 patients who discontinued FK506, which further confirmed the safety of FK506 alone. Together with our previous report on the upper limit of FK506(17 ng/mL)and these results, we recommend the optimal serum concentration of FK506 to range from 13 to 17 ng/ mL.

In this study, we investigated the level of gut absorption following oral beclomethasone dipropionate (BDP) administration by measuring the blood concentration of its metabolites measured by LC-MS/MS using the HPLC method. Five patients who were administered BDP orally for gut GVHD were included. The blood concentrations of beclomethasone-17-monopropionate (17BMP), which is one of the active metabolites of BDP, were 618 approximately 1, 749 pg/mL in 4 of the studied 5 patients, which was comparable to that after inhalation of BDP; however, it was relatively higher in one patient (2,439+/-161 pg/mL). As the blood concentration of 17BMP in this study patient was higher compared with healthy volunteers administered a single oral BDP 4 mg, GVHD patients might have a higher concentration than healthy volunteers. Given that a higher grade of gut GVHD was associated with a higher blood level of 17BMP, BDP absorption might be associated with gut mucosal injury. Thus, the systemic adverse effect following oral BDP administration might not be negligible especially in gut GVHD patients.

Multidrug-resistant Pseudomonas aeruginosa (MDRP), defined as Pseudomonas aeruginosa resistant to aminoglycosides, carbapenems, and fluoroquinolones, has emerged as an increasingly problematic cause of hospital-acquired infection. With parenteral colistin unavailable in Japan, effective antimicrobial options are severely limited. We report a case of MDRP bacteremia successfully treated with antibiotic combination therapy screened by a 'Break-point Checkerboard Plate'. A 54-year-old man with malignant lymphoma who became febrile 9 days after a recent course of chemotherapy had a neutrophil count of 176/microL. Treatment with meropenem and vancomycin was ineffective and high fever persisted. Methicillin-resistant Staphylococcus aureus (MRSA) and MDRP were isolated from blood culture and combination therapy with aztreonam and amikacin was selected for MDRP based on 'Break-point Checkerboard Plate' results. Linezolid was used for MRSA. The patient recovered successfully from MDRP and MRSA sepsis.

To disclose the information for the risk in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we propose a new concept of the risk in allo-HSCT. We analyzed all 94 allo-HSCT cases (86 patients) in our hospital since 1983. The overall survival rate was 56.4%. Among 27 patients considered to be at standard risk judged by conventional risk criteria who underwent initial transplantation from HLA-identical donors, 66.7% of them survived. Univariate statistical analyses among subgroups classified by conventional risk criteria and several reported prognostic factors show significant differences. However, all of them failed to show significant difference because of too much variation between cases in the same subgroup or a too small number of patients as compared with the U.S.A or European transplantation centers. We propose an alternative comprehensive classification of transplantation risk according to two newly-recognized distinct risks, disease state and transplantation risk. This comprehensive classification revealed significance in the multivariate statistical analyses in our hospital. We expect further discussion or the appearance of other beneficial nationwide proposals to evaluate and disclose the risk affecting survival following allo-HSCT.