Takuya Yamashita

Comparison of Allogeneic Hematopoietic Cell Transplantation and Chemotherapy in Elderly Patients with Non-M3 Acute Myelogenous Leukemia in First Complete Remission

The benefits of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with acute myelogenous leukemia (AML) in first complete remission (CR1) have mostly been evaluated in younger patients. Although favorable outcomes of allo-HCT over chemotherapy have been reported with the use of reduced-intensity conditioning (RIC) regimens in elderly patients with AML in CR1, information is still limited, especially on the effects of cytogenetic risks and donor sources. We collected data from AML patients aged 50 to 70 years who achieved CR1, and compared the outcome in 152 patients who underwent allo-HCT in CR1 (HCT group) to that in 884 patients who were treated with chemotherapy (CTx group). The cumulative incidence of relapse in the HCT group was significantly lower than that in the CTx group (22% versus 62%). Both overall survival (OS) and relapse-free survival (RFS) were significantly improved in the HCT group (OS: 62% versus 51%, P = .012), not only in the whole population, but also in the intermediate-risk group. Among patients who had a suitable related donor, the outcomes in the HCT group were significantly better than those in the CTx group. The introduction of appropriate treatment strategies that include allo-HCT may improve the outcome in elderly patients with AML in CR1.

A Markov decision analysis of allogeneic hematopoietic cell transplantation versus chemotherapy in patients with acute myeloid leukemia in first remission

Various prospective trials have been performed to assess the roles of allogeneic hematopoietic cell transplantation (allo-HCT) and chemotherapy in patients with acute myeloid leukemia (AML) in first complete remission (CR1). However, the results have not always been consistent, and there has been a limited evaluation of quality of life (QOL) in these postremission strategies. We performed a Markov decision analysis that enabled us to compare survival outcomes with a QOL evaluation using a database of 2029 adult AML patients who achieved CR1. The Markov decision model compared 2 strategies: allo-HCT or chemotherapy in CR1. Patients who had intermediate- or unfavorable-risk AML had a longer life expectancy when they received allo-HCT in CR1 than patients treated with chemotherapy alone. Likewise, patients who had a suitable related donor who received allo-HCT in CR1 had a longer life expectancy. The life expectancy was shortened to a greater degree by adjustment for QOL in the allo-HCT group. Nevertheless, QOL-adjusted life expectancies in most of the subgroups remained longer in the allo-HCT group than in the chemotherapy group. Our results showed that older patients with a related donor and younger patients with unfavorable cytogenetics benefited the most from allo-HCT in CR1.

Eight-year follow-up of patients with immune thrombocytopenic purpura related toH. pyloriinfection

Thrombocytopenia related to Helicobacter pylori infection is a definitive subset of chronic immune thrombocytopenic purpura (ITP) but its long-term prognosis has not been evaluated extensively. The possibility of recurrence of thrombocytopenia after re-infection of H. pylori is another concern. We evaluated 8-year follow-up data for 11 patients with ITP related to H. pylori infection in a single institution. In 2001, patients with chronic ITP were evaluated for H. pylori infection at the Tokyo Metropolitan Komagome Hospital using 13C urea breath test (UBIT). Nineteen patients turned out to be positive and were treated for H. pylori infection. Platelet count 6 months after treatment revealed complete response (CR) in 10 patients and response in one patient. Eight years later, 17 of these 19 patients were re-evaluated for H. pylori infection and platelet count. Platelet counts of the 11 previous responders remained to indicate CR. Two of 13 patients re-examined by UBIT showed positive results and one of these two patients continued to keep normal platelet count. Nonetheless, the prognosis of patients who responded to eradication was excellent.

Incapacitating Lower Limb Pain Syndrome in Cord Blood Stem Cell Transplant Recipients with Calcineurin Inhibitor

Calcineurin-inhibitor induced pain syndrome (CIPS) is a newly described entity with a characteristic feature of sudden onset of severe lower limb pain, and high levels of cyclosporine or tacrolimus may be involved in the pathogenesis. This syndrome is rarely seen in recipients of hematopoietic stem cell transplantation (HSCT) compared with other organ transplant recipients, however, heightened awareness of this complication after HSCT may be needed for hematologists, as misdiagnosis can result in catastrophic consequences. We report herein two cases of lower limb pain syndrome, with some clinical features resembling CIPS, occurring during the early phase of cord blood stem cell transplantation for hematological malignancy.

MmTRA1b/phospholipid scramblase 1 gene expression is a new prognostic factor for acute myelogenous leukemia

We previously found that expression of the Mm-1 cell-derived transplantability-associated gene 1b (MmTRA1b)/phospholipid scramblase 1 gene was markedly induced during the granulocytic differentiation of human myeloid leukemia cells. To evaluate the role of MmTRA1b expression in human myeloid leukemia, we investigated the relative levels of MmTRA1b transcripts in 81 patients with acute myelogenous leukemia (AML) by the reverse transcriptase polymerase chain reaction. The expression of MmTRA1b in AML-M1, -M5a and -M5b was significantly lower than that in normal bone marrow cells. The levels of MmTRA1b expression in AML-M2 and -M4 varied among patients. Higher MmTRA1b mRNA levels were associated with significantly longer overall survival in AML, especially in AML-M4 patients, independent of chromosomal aberrations such as t(8;21) and inv(16). The present results suggest that the MmTRA1b mRNA level is a new prognostic factor for AML, especially the AML-M4 subtype.

Intracranial hemorrhage following allogeneic hematopoietic stem cell transplantation

Charts and radiographs of 622 allogeneic hematopoietic stem cell transplant (HSCT) recipients, over a 20‐year period, were retrospectively reviewed for intracranial hemorrhage (ICH) following transplant. A total of 21 cases of ICH were identified (3.4%) including 15 cases of intraparenchymal hemorrhage (IPH), two cases of subarachnoid hemorrhage (SAH), and four cases of subdural hematoma (SDH). The median time from transplantation to the onset of ICH was 63 days (range, 6–3,488 days). The clinical features of post‐transplant ICH patients were similar and included hypertension, diabetes mellitus, chronic graft‐versus‐host disease (GVHD), systemic infection, and veno occlusive disease (VOD), recently referred to as sinusoidal obstruction syndrome, in addition to severe thrombocytopenia. Mortality rate was especially high (89%) after IPH with a median survival of 2 days (range, 0–148 days). In contrast, all patients with SAH or SDH following HSCT survived. The cause of post‐transplant ICH appears to be multifactorial, including thrombocytopenia, hypertension, acute GVHD, VOD, and radiation therapy. Most patients in our series displayed severe thrombocytopenia at the onset of ICH, even though adequate prophylactic platelet transfusions were given. By univariate analysis, cord blood transplantation, acute GVHD, systemic infection, and VOD were related to the incidence of ICH, whereas prior CNS episodes and radiation therapy did not reach statistical significance. A multivariate analysis with logistic regression identified acute GVHD as the only factor that significantly influenced ICH occurrence. Am. J. Hematol. 2009.

Stenotrophomonas maltophilia infection in hematopoietic SCT recipients: High mortality due to pulmonary hemorrhage

To clarify the clinical features and outcome of Stenotrophomonas maltophilia infection among hematopoietic SCT (HCT) recipients, we retrospectively reviewed the records of 1085 consecutive HCT recipients and identified 42 episodes in 31 HCT recipients with S. maltophilia infection. We compared these recipients with 30 non-HCT patients with S. maltophilia infection. The mortality rate in HCT recipients was significantly higher than that in non-HCT patients (relative risk 5.7, P=0.04), and we identified seven patients with pulmonary hemorrhage due to S. maltophilia, exclusively in the HCT cohort. Six of these latter seven patients died within 1 day from the onset of hemorrhage and the isolate was identified after death in most cases; one patient, who received empiric therapy for S. maltophilia and granulocyte transfusion, survived for more than 2 weeks. The patients with pulmonary hemorrhage had a more severe and longer duration of neutropenia, persistent fever despite of the use of broad-spectrum antibiotics, complication by pneumonia and higher C-reactive protein levels than those without pulmonary hemorrhage. In conclusion, S. maltophilia was associated with fulminant and fatal pulmonary hemorrhage in HCT recipients. Empiric therapy with antibiotics before the onset of pulmonary hemorrhage may be effective in HCT recipients who carry the conditions identified.

A randomized controlled trial of plasma real-time PCR and antigenemia assay for monitoring CMV infection after unrelated BMT

Preemptive therapy is the standard strategy for preventing CMV disease after allogeneic hematopoietic SCT. In this study, unrelated BMT recipients were randomly assigned to a plasma real-time PCR group or an antigenemia group to compare the value of these monitoring tools for CMV reactivation. Ganciclovir (GCV) was started at 5 mg/kg/day when PCR reached 300 copies per ml or when antigenemia reached three positive cells per two slides. A total of 88 patients were randomized into the antigenemia group (n=45) or the PCR group (n=43). A significantly higher number of patients reached the threshold in the antigenemia group than in the PCR group (73.3 vs 44.2%, P=0.0089). However, only three patients (one in the antigenemia group and two in the PCR group) developed early CMV disease. These patients exclusively had colitis and were successfully treated with GCV or foscarnet. The median number of antigenemia-positive cells at the start of GCV was 47 in the PCR group. These findings suggest that antigenemia assay with the current cutoff was too sensitive and led to unnecessary use of GCV. However, the appropriateness of the threshold may be different by the methodology used, and therefore, it is difficult to generalize.

Fatal intracranial hemorrhage following administration of recombinant thrombomodulin in a patient after cord blood transplantation

Fatal intracranial hemorrhage following administration of recombinant thrombomodulin in a patient after cord blood transplantation

Mortality and medical morbidity beyond 2 years after allogeneic hematopoietic stem cell transplantation: experience at a single institution

Long-term follow-up data on patients who underwent allogeneic hematopoietic stem cell transplantation in our institution between 1990 and 2007 were evaluated for mortality and morbidity beyond 2 years post-transplantation. Follow-up data were obtained annually from medical records or by mail to the relevant hospitals, or to the patients themselves. In total, 369 patients survived more than 2 years, but 72 patients died thereafter. Relapse was the most common cause of death, followed by pulmonary complications and infections. Second malignancy was the cause of death in seven patients. Chronic kidney disease was one of the most serious complications, and seven patients needed regular dialysis or kidney transplantation. Hypertension and diabetes were reported in 19 and 11.2% patients, respectively. Second malignancies were observed in 14 patients beyond 2 years after transplantation, and the oral mucosa, tongue, esophagus and colon were the main organs involved. We recommend that physicians caring for allogeneic hematopoietic stem cell transplant patients should at a minimum examine kidney function and gastrointestinal tract for secondary malignancy, in addition to hematological status. Such information will be useful for optimizing outcomes through the detection and prevention of complications.