GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia.

To investigate better GVHD prophylaxis in reduced intensity conditioning umbilical cord blood transplantation (RIC-UCBT), we compared transplant outcomes after UCBT among GvHD prophylaxes using the registry data. We selected patients transplanted for AML or ALL with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 748 first RIC-UCBT between 2000 and 2012 (MTX+ group, 446, MMF+ group, 302) were included. The cumulative incidence of neutrophil and platelet counts higher than 50 000/µL was significantly better in the MMF+ group (relative risk (RR), 1.55; P<0.001: RR, 1.34; P=0.003, respectively). In multivariate analyses, the risk of grade II-IV and III-IV acute GvHD was significantly higher in the MMF+ group than in the MTX+ group (RR, 1.75; P<0.001: RR, 1.97; P=0.004, respectively). In disease-specific analyses of AML, the risk of relapse of high-risk disease was significantly lower in the MMF+ group (RR, 0.69; P=0.009), whereas no significant difference was observed in the risk of relapse-free and overall survival in high-risk disease. In patients with standard-risk disease, no significant differences were noted in the risk of relapse or survival between the MTX+ and MMF+ groups. Collectively, these results suggest that MMF-containing prophylaxis may be preferable in RIC-UCBT, particularly for high-risk disease.

Impact of graft-versus-host disease on outcomes after unrelated cord blood transplantation.

The effect of graft-versus-host disease (GVHD) on transplant outcomes after unrelated cord blood transplantation (UCBT) has not been fully elucidated. We analyzed the impact of acute and chronic GVHD on outcomes in adult patients with acute leukemia or myelodysplastic syndrome who underwent their first UCBT (n=2558). The effect of GVHD on outcomes was analyzed after adjusting for other significant variables. The occurrence of GVHD was treated as a time-dependent covariate. The occurrence of grade 1-2 or 3-4 acute GVHD was significantly associated with a lower relapse rate. Grade 3-4 acute GVHD was associated with a higher risk of non-relapse and overall mortality than no acute GVHD, whereas grade 1-2 acute GVHD was associated with a lower risk of non-relapse and overall mortality than no acute GVHD. Limited or extensive chronic GVHD was significantly associated with a lower relapse rate. Limited chronic GVHD was associated with a lower overall and non-relapse mortality than no chronic GVHD. In conclusion, mild acute or chronic GVHD was associated not only with a low risk of relapse but also with a low risk of non-relapse mortality, and provides a survival benefit in UCBT.

Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil.

In order to examine GvHD prophylaxis in umbilical cord blood transplantation (UCBT) in more detail, we compared transplant outcomes after UCBT for acute leukemia among GvHD prophylaxes using registry data. We selected patients transplanted with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 1516 first myeloablative UCBT between 2000 and 2012 (Cyclosporine A (CyA) plus MTX, 824, Tacrolimus (Tac) plus MTX, 554, Tac plus MMF, 138) were included. With adjusted analyses, Tac plus MMF showed a significantly higher risk for grade II-IV and III-IV acute GvHD than CyA or Tac plus MTX. Although NRM was similar, Tac plus MMF showed a significantly lower risk of relapse than CyA or Tac plus MTX. A significant difference was observed in the risk of overall mortality (OM) between the MTX-containing group and MMF-containing group. In patients with standard-risk disease, there was no significant difference in the risk of OM in any GvHD prophylaxis. However, in patients with advanced-risk disease, Tac plus MMF showed a significantly lower risk of OM. Therefore, MTX-containing prophylaxis is preferred in UCBT for standard-risk disease, whereas MMF-containing prophylaxis is preferred for advanced-risk disease. A prospective study to identify optimal GvHD prophylaxis for UCBT is warranted.

Early application of related SCT might improve clinical outcome in adult T-cell leukemia/lymphoma.

Allogeneic hematopoietic SCT (allo-HSCT) is a curative treatment for aggressive adult T-cell leukemia/lymphoma (ATLL). Considering the dismal prognosis associated with conventional chemotherapies, early application of allo-HSCT might be beneficial for patients with ATLL. However, no previous study has addressed the optimal timing of allo-HSCT from related donors. Hence, to evaluate the impact of timing of allo-HSCT for patients with ATLL, we retrospectively analyzed data from patients with ATLL who received an allo-HSCT from a related donor. The median age was 52 years. Patients were grouped according to the interval from diagnosis to allo-HSCT: early transplant group, <100 days, n=72; late transplant group, ⩾100 days, n=428. The corresponding constituents of disease status were not statistically different between the two groups (P=0.11). The probability of OS in the early transplant group was significantly higher than that in the late transplant group (4-year OS, 49.3% vs 31.2%). Multivariate analysis revealed that late allo-HSCT was an unfavorable prognostic factor for OS (hazard ratio, 1.46; 95% confidence interval (CI), 1.01-2.11; P=0.04). Despite the limitations of a retrospective study, it might be acceptable to consider early application of allo-HSCT for ATLL.

Relative incidences and outcomes of Clostridium difficile infection following transplantation of unrelated cord blood, unrelated bone marrow, and related peripheral blood in adult patients: a single institute study.

BACKGROUND: Clostridium difficile is a major cause of nosocomial diarrhea. The incidence and prognosis of C. difficile-associated diarrhea (CDAD) has not yet been assessed in adult patients after unrelated cord blood transplantation (uCBT). METHODS: The medical records of 135 adult unrelated cord blood transplant recipients were reviewed retrospectively to investigate the clinical features of CDAD after uCBT. These data were compared to medical records of 39 unrelated bone marrow transplant recipients and 27 related peripheral blood stem cell transplant recipients as controls. RESULTS: A total of 17 recipients developed CDAD, with onset occurring at a median of 22 days (range, 0-56 days) after transplantation. Among the unrelated cord blood transplant recipients, 11 (9%) developed CDAD. These results were comparable with those of CDAD after unrelated bone marrow transplantation (uBMT) (2/39, 6%) and related peripheral blood stem cell transplantation (rPBSCT) (4/27, 16%) (P=0.37). Fifteen of the infected recipients were successfully treated with oral metronidazole, vancomycin, or cessation of antibiotics. The remaining 2 recipients who developed CDAD after uCBT died of other causes. The development of CDAD did not negatively affect overall survival after uCBT. CONCLUSIONS: These data indicate that the incidence and prognosis of CDAD after uCBT are comparable with those after uBMT and rPBSCT.

Visceral varicella zoster virus infection after allogeneic stem cell transplantation.

INTRODUCTION: Varicella zoster virus (VZV) disease is one of the major infectious complications that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Many reports have shown visceral VZV infection, a special type of VZV disease, to be rare. However, few studies so far have included a large number of patients. FINDINGS: Visceral VZV infection was found in 20 (0.8%) of 2411 patients who underwent allo-HSCT at our hospitals. Seventeen (85%) patients were taking immunosuppressive agents at the time of presentation with zoster. The presenting symptom was abdominal pain in 16 patients (80%), unconsciousness in 3 patients (15%), and no symptoms in 1 patient. The mean time interval from allo-HSCT to symptomatic visceral VZV infection was 273 days (103-800 days). The eruptions appeared within 3 days (0-13) after the first symptoms. Treatment with intravenous acyclovir was initiated before the appearance of eruptions in 3 of 18 patients (all 3 survived) with vesicular eruptions, the same day in 12 patients (11 survived, 1 died), and after the appearance in 3 patients (1 survived, 2 died). The overall mortality was 20%. CONCLUSION: In conclusion, these data confirm that the incidence of visceral VZV infection is infrequent, but this disease is serious. When patients being treated with immunosuppressive agents demonstrate abdominal pain or unconsciousness, the possibility of visceral VZV infection should be considered as well as earlier therapeutic intervention.

Rapidly progressive fatal hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in hematologic malignancy.

BACKGROUND: Pneumonia caused by Stenotrophomonas maltophilia is rare, but can be lethal in severely immunocompromised patients. However, its clinical course remains unclear. PATIENTS AND METHODS: Patients with pneumonia caused by S. maltophilia in Toranomon Hospital (890 beds, Tokyo, Japan) were reviewed retrospectively between April 2006 and March 2010. RESULTS: During the study period, 10 cases of S. maltophilia pneumonia were identified. Seven patients had acute myeloid leukemia, 2 had myelodysplastic syndrome, and 1 had malignant lymphoma. All patients developed symptoms after allogeneic hematopoietic stem cell transplantation (HSCT). Five patients received first cord blood transplantation (CBT), 4 patients received second CBT, and 1 patient received first peripheral blood stem cell transplantation (PBSCT). The overall incidence of S. maltophilia pneumonia among 508 patients who received HSCT during the period was 2.0%. The incidence was 0% (0/95) in patients after bone marrow transplantation, 0.8% (1/133) after PBSCT, and 3.2% (9/279) after CBT. Pneumonia developed a median of 13.5 days (range, 6-40) after transplantation. At onset, the median white blood cell count was 10/µL (range, 10-1900), and the median neutrophil count was 0/µL (range, 0-1720). In all patients, S. maltophilia bacteremia developed with bloody sputum or hemoptysis. The 28-day mortality rate was 100%; the median survival after onset of pneumonia was 2 days (range, 1-10). CONCLUSIONS: Hemorrhagic S. maltophilia pneumonia rapidly progresses and is fatal in patients with hematologic malignancy. Attention should be particularly paid to the neutropenic phase early after HSCT or prolonged neutropenia due to engraftment failure. A prompt trimethoprim-sulfamethoxazole-based multidrug combination regimen should be considered to rescue suspected cases of S. maltophilia pneumonia in these severely immunosuppressed patients.

The effectiveness of walking as an intervention for low back pain: a systematic review.

As current low back pain (LBP) guidelines do not specifically advocate walking as an intervention, this review has explored for the effectiveness of walking in managing acute and chronic LBP. CINAHL, Medline, AMED, EMBASE, PubMed, Cochrane and Scopus databases, as well as a hand search of reference lists of retrieved articles, were searched. The search was restricted to studies in the English language. Studies were included when walking was identified as an intervention. Four studies met inclusion criteria, and were assessed with a quality checklist. Three lower ranked studies reported a reduction in LBP from a walking intervention, while the highest ranked study observed no effect. Heterogeneity of study design made it difficult to draw comparisons between studies. There is only low-moderate evidence for walking as an effective intervention strategy for LBP. Further investigation is required to investigate the strength of effect for walking as a primary intervention in the management of acute and chronic LBP.

Identification of molecular markers for pre-engraftment immune reactions after cord blood transplantation by SELDI-TOF MS.

Cord blood transplantation (CBT) is frequently associated with pre-engraftment immune reaction (PIR), which is characterized by high-grade fever that peaks around day 9 of transplantation. PIR mimics hyperacute GVHD or engraftment syndrome; however, it is considered to be of different etiology as it occurs before engraftment. Proteomic patterns have been studied in the fields of transplantation, but no specific marker has been identified. As there are no data to confirm the mechanism of PIR, we used a surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF MS) system to identify a specific marker for PIR. The protein expression profile of serum samples from CBT patients was analyzed with a SELDI-TOF MS system. A protein peak that commonly predominated in PIR was purified by an anion exchange column, isolated by SDS-PAGE, and identified by in-gel trypsin digestion, and mass fingerprinting. A 8.6-kDa protein and 11-kDa protein that increased by 10- to 100-fold in the serum of patients during PIR was identified as anaphylatoxin C4a and serum amyloid A. SELDI-TOF MS system in combination with other proteomic methods could serve as a potential diagnostic tool in discovering biomarkers for PIR after CBT.

A survey of adult victims of dog bites in New Zealand.

AIM: To describe the circumstances of dog bites to adults in New Zealand, in order to better understand factors associated with these bites. METHODS: A questionnaire was sent to 1,800 adults aged > or =16 years who had made claims to the Accident Compensation Corporation (ACC) in 2002 as a result of dog bites. RESULTS: Five hundred and thirty-five questionnaires were returned; 50% of respondents were male, and 30% of bites were reported to local authorities. Most injuries were to the legs or hand. More people were bitten by male dogs than female dogs. A disproportionate number of bites took place in rural areas, but the most common locations for attacks were streets/walkways, and the victim's home. Protection of territory, accidental bites, fear, and pain were considered to be the most common reasons for dogs to bite. CONCLUSION: Many victims were bitten in situations that could have been avoided.

The long-term survival rate of catecholamine-resistant septic shock in Japanese patients who received vasopressin therapy.

BACKGROUND: Septic shock is associated with vasopressin deficiency and hypersensitivity to its exogenous administration. The aim of this study is to review the 28-day survival rate, hemodynamic and renal effects of vasopressin therapy in refractory septic shock Japanese patients. METHODS: 55 Japanese patients experiencing catecholamine-resistant septic shock were treated with vasopressin. Hemodynamic alterations and the serum concentrations of aspartate aminotransferase, total bilirubin and creatinine clearance were evaluated following vasopressin treatment. RESULTS: In both, survivors and non-surviving patients, treatment with vasopressin resulted in a significantly increase in mean arterial pressure, hourly urine output, and a significant decrease in heart rate and total pressor dosage requirements. Creatinine clearance was significantly increased only in survivors. There were no significant changes in the serum concentrations of aspartate aminotransferase and total bilirubin. The 28-day survival rate was 45% (25 patients). CONCLUSIONS: In Japanese septic shock patients, vasopressin infusion improved hemodynamic status and reduced catecholamine requirement, and 28-day survival rate was 45%.

Reduced dose of foscarnet as preemptive therapy for cytomegalovirus infection following reduced-intensity cord blood transplantation.

Although foscarnet is a promising alternative for the treatment of cytomegalovirus (CMV) infection, its toxicity can be significant in patients with advanced age. We retrospectively reviewed medical records of 123 patients (median age of 55; range, 17-79) who received reduced-intensity cord blood transplantation (RI-CBT). Patients preemptively received reduced-dose foscarnet 30 mg/kg twice daily when CMV antigenemia exceeded 10/50,000. Sixty-three patients developed CMV antigenemia on a median of day 34, and 29 received foscarnet preemptively. The median level of CMV antigenemia at the initiation of foscarnet was 30. Median duration of foscarnet administration was 24 days. Adverse effects included electrolyte abnormalities (n=19), renal impairment (n=13), and skin eruption requiring discontinuation of foscarnet (n=1). Preemptive therapy of foscarnet was completed in 18 patients. Seven patients died during foscarnet use without developing CMV disease. The remaining 3 developed CMV enterocolitis 5, 14, and 17 days after initiation of foscarnet. All of them were successfully treated with ganciclovir or foscarnet. Reduced dose of foscarnet is beneficial to control CMV reactivation following RI-CBT; however, it has considerable toxicities in RI-CBT recipients with advanced age. Further studies are warranted to minimize toxicities and identify optimal dosages.