Tomoyasu Jo

Risk factors for and prognosis of hemorrhagic cystitis after allogeneic stem cell transplantation: Retrospective analysis in a single institution

Abstract Hemorrhagic cystitis (HC) is a major complication after allogeneic stem cell transplantation (allo-SCT) and can be life threatening. To analyze risk factors and prognosis, we retrospectively reviewed 249 cases receiving allo-SCT in our institution. Median age was 47 years (13–72 years). Disease status at SCT was progressive in 73 cases. Conditioning was myeloablative (MAC) in 146 cases. Acute graft-versus-host disease (aGVHD) grade II–IV treated with prednisolone occurred in 82 cases, and cytomegalovirus (CMV) was reactivated in 91 cases. HC was reported in 47 cases at a median of 35 days (7–469 days) after SCT, and 34 (72.3%) cases recovered after a median of 19.5 days (2–252 days). In univariate analysis, the identified risk factors for HC included age over 45 years, progressive disease status, MAC, aGVHD treated with prednisolone, and CMV reactivation. In multivariate analysis, older age, MAC, and CMV remained independent predictors (hazard ratios: 2.35, 3.50, and 2.87). In patients with severe HC, percentage recovery was lower (3 in 13 cases; 23.1%) and the median duration was longer (54 days) than in those with moderate HC (31 in 36 cases; 86.1%, 17 days, P < 0.01). Treatment-related mortality was also higher (59.1%, P = 0.03) and overall survival was poorer (16.7%, P < 0.01) at 1 year after SCT. Prospective studies should be started considering prophylactic antiviral administration in high-risk patients such as those identified in this study.

Efficacy of antithymocyte globulin for allogeneic hematopoietic cell transplantation: a systematic review and meta-analysis.

Abstract The efficacy of rabbit antithymocyte globulin (ATG) for the prevention of graft-versus-host disease (GVHD) has been evaluated in several randomized control trials, but the results show some discrepancies. Therefore, we performed a systematic review and meta-analysis covering the latest RCTs including six trials (total 845 patients). The incidence of acute and chronic GVHD was significantly lower in the ATG arms (risk ratio, 0.75 and 0.54, respectively). No significant differences were found regarding overall survival, the incidence of relapse, and non-relapse mortality; however, the incidence of cytomegalovirus and Epstein-Barr virus reactivation increased (risk ratio, 1.25 and 1.33), and neutrophil engraftment was significantly delayed (median, 2.66 days). In conclusion, rabbit ATG should be beneficial as a GVHD prophylaxis in addition to conventional regimens, with close monitoring of virus reactivation and enough attention to delayed engraftment. Studies comparing the timing and dosage of ATG are essential to determine the suitable prophylactic regimens.

Hairy Cell Leukemia with Systemic Lymphadenopathy: Detection of BRAF Mutations in Both Lymph Node and Peripheral Blood Specimens

A 47-year-old woman with pancytopenia, excessive systemic lymphadenopathy and splenomegaly was referred to our hospital. The peripheral blood (PB) smear findings indicated neutropenia with lymphoid cells exhibiting hairy projections, while the histological findings of the cervical lymph node (LN) suggested hairy cell leukemia (HCL). In addition, the BRAF V600E mutation was detected, and the immunoglobulin gene rearrangement patterns were identical in both the cervical LN and PB specimens. Based on these findings, we diagnosed the patient with systemic lymphadenopathy due to HCL. This is the first report of a BRAF mutation detected in both the PB and LN at the onset of HCL.

Comparison of up-front treatments for newly diagnosed immune thrombocytopenia -a systematic review and network meta-analysis

Corticosteroids such as prednisolone and dexamethasone have been established as up-front therapy for the treatment of newly diagnosed immune thrombocytopenia. Recent studies have indicated that other treatments such as rituximab or thrombopoietin receptor agonist can also be effective choices. We performed a systematic review and network meta-analysis to establish a clinically meaningful hierarchy of efficacy and safety of treatments for newly diagnosed primary immune thrombocytopenia in adults. Randomized controlled trials evaluating medical treatments for newly diagnosed immune thrombocytopenia were included. Reviewers independently extracted data and assessed the risk of bias. The main outcome was the sustained response (platelet count >30×109/L for 3–6 months after completion of treatments), while overall response (platelet count >30×109/L for 2–4 weeks after initiation of the up-front treatment) and therapy-related adverse events were the secondary endpoints. A total of 21 randomized controlled trials (1898 patients) were included in this study. Our main findings were a significantly better sustained response in the recombinant human thrombopoietin+dexamethasone and rituximab+dexamethasone arms compared to those of conventional therapies (prednisolone and dexamethasone monotherapy). Moreover, recombinant human thrombopoietin+dexamethasone and +prednisolone improved early overall response compared to prednisolone, dexamethasone, and rituximab-containing regimens. Therapy-related adverse events showed similar profiles and were tolerable in all treatment arms. Regimens containing recombinant human thrombopoietin agonist may be beneficial up-front therapies in addition to the conventional corticosteroid monotherapies. Future head-to-head trials including these regimens and rituximab-containing treatments are necessary in order to overcome the limitations of the small number in our study and determine the most suitable initial therapies for newly diagnosed immune thrombocytopenia.

Chronic Kidney Disease in Long-Term Survivors after Allogeneic Hematopoietic Stem Cell Transplantation: Retrospective Analysis at a Single Institute

The number of patients eligible for allogeneic stem cell transplantation (allo-HSCT) has increased because of improvements in transplantation procedures. Among long-term survivors of allo-HSCT, chronic kidney disease (CKD) is a major cause of morbidity. We retrospectively analyzed the clinical data of 106 consecutive patients with a median age of 43 years (range, 17 to 73) who had undergone allo-HSCT at our institution between January 2001 and September 2009. Patients who died within 5 years after transplantation or had CKD at the time of transplantation were excluded from study. CKD was defined as a persistent decrease in the estimated glomerular filtration rate to below 60 mL/min/1.73 m2. CKD occurred in 32 patients (30.2%) at a median time of 55 months after transplantation. Three patients required maintenance hemodialysis. In multivariate analysis older age at the time of transplantation (hazard ratio [HR], 1.07/year; 95% confidence interval [CI], 1.02 to 1.13) and a history of acute kidney injury (AKI) within 100 days after transplantation (HR, 6.30; 95% CI, 2.21 to 17.9) were significant risk factors for CKD. Conditioning regimen, stem cell source, or the presence of acute/chronic GVHD was not significantly associated with CKD in this study. Patients with CKD had a lower overall survival rate (HR, 4.11; 95% CI, 1.3 to 13.0) than patients without CKD. Careful monitoring of renal function is required for long-term survivors after allo-HSCT, especially in patients who have experienced AKI and in older patients.

Response to the Comment by Cirasino L and Semeraro S: “Need to direct immune thrombocytopenia therapy towards shared goals” Direct and indirect comparisons to determine the first choice for newly diagnosed primary immune thrombocytopenia in adults

In our previous study published in Haematologica,[1][1] we attempted to establish a clinically meaningful hierarchy of efficacy and safety of treatments for newly diagnosed primary immune thrombocytopenia (ITP) in adults, including all the randomized controlled studies (RCTs) available and

Efficacy of Dexamethasone for Acute Primary Immune Thrombocytopenia Compared to Prednisolone: A Systematic Review and Meta-analysis

Corticosteroids have been established as first-line therapy in acute primary immune thrombocytopenia (ITP), and the clinical guidelines recommend either dexamethasone (Dex) or prednisolone (PSL). The types and dosages of corticosteroids, however, have not yet been determined, because previous randomized control trials (RCTs) comparing Dex and PSL showed controversial results in terms of efficacy. To understand and interpret all available evidence, we conducted a systematic review and meta-analysis of RCTs. The main outcome measure was the incidence of sustained response (SR; platelet count >30 × 10 9 /L for 6 months without concomitant treatments after the completion of the final therapies). Eight RCTs (totaling 704 patients) were included in this study. The incidence of SR showed no significant difference, while it was significantly higher in the Dex arm when used with posttherapy (more than one course of Dex or tapering corticosteroids added; risk ratio [RR], 1.82; 95% confidence interval [CI], 1.38–2.41; p  < 0.01). A single course of Dex showed no significant difference. The overall response (platelet >30 × 10 9 /L) at day 28 was significantly improved in the Dex arm (RR, 1.11; 95% CI, 1.01–1.22; p  = 0.03) and Dex with posttherapy suppressed long-term relapse (RR of nonevent, 1.32; 95% CI, 1.10–1.59; p  < 0.01). There were significantly fewer adverse events in the Dex arm (RR, 0.45; 95% CI, 0.37–0.55; p  < 0.01). Use of Dex with posttherapy instead of PSL may be more beneficial as the initial therapy. Studies comparing Dex with other new strategies are essential to determine the most suitable therapeutic regimens for acute ITP.

Myeloid blast crisis in chronic myeloid leukemia with a unique deletion near the BCR/ABL breakpoint

We describe a case of a 44-year-old man with chronic myeloid leukemia in blastic crisis phase based on peripheral blood smear findings, and the detection of BCR/ABL transcript signals by fluorescence in situ hybridization analysis. Our attempts to quantify the amount of the major BCR/ABL fusion gene revealed that some primers were unable to detect the gene, whereas other primers could detect the gene. We detected a unique deletion on the BCR area by cloning the sequence, which has not been reported previously. Our case suggests that direct sequencing is important when quantitative PCR yields ambiguous results.