Clinical Outcome of Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph + ALL): Experience From a Single Institution

To identify factors affecting transplant outcome, data from 65 Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients who had undergone allogeneic hematopoietic transplantation (allo-HSCT) in our institution were analyzed. The probability of OS (overall survival) and DFS (disease free-survival) at 3 years after allo-HSCT was 40.1 % and 38 %, respectively. Multivariate analysis showed that gender and disease status (p?=?0.0059, p?=?0.0039, respectively) were significant factors for OS. Among 51 patients with CR (complete remission), multivariate analysis showed that the factors associated with OS included gender (p?=?0.014), number of white blood cell at diagnosis (p?=?0.025), and the source of stem cells (bone marrow <BM >versus. cord blood; BM stem cell source was associated with favorable OS, p?=?0.042). Twenty-one patients relapsed after allo-HSCT with a median of 207 days (range, 19–1,324 days). The estimated cumulative incidence of relapse at 3 years was 39.4 %. Patients with CR showed a lower relapse rate at 3 years (34.2 %) when compared with patients with non-CR (62.7 %). Among 21 patients, eight patients received imatinib-based chemotherapy and 13 received chemotherapy without imatinib before HSCT. In terms of treatment after relapse, seven patients received chemotherapy with imatinib and 13 received chemotherapy without imatinib. Five patients underwent a second HSCT. One patient survived, and 20 patients died. In this study, disease status at time of allo-HSCT had a significant impact on OS, DFS, and relapse. Imatinib administration given before allo-HSCT was not associated with favorable outcome. Second-generation tyrosine kinase inhibitors may be more suitable candidates for Ph + ALL before and after allo-HSCT.     

Squamous cell carcinoma of the anal canal showing pathological complete response after S-1 plus radiotherapy -a case report

The patient was a 53-year-old woman who underwent colonoscopy for anal pain and melena. We diagnosed her with Stage I (T2N0M0) anal canal squamous cell carcinoma by biopsy specimen and CT scan. We recommended chemo-radiotherapy because she hoped to keep her anus. For this patient, we planned an S-1 administration at a dose of 120 mg/ body/day for consecutive 14 days followed by 7 days of rest period with whole pelvis and bilateral inguinal radiation (total 45 Gy/25 Fr). Then we added a booster radiation (14 Gy/7 Fr) to a local area for 5 days followed by 2 days of rest period. After 2 weeks of chemo-radiotherapy, we could not detect any tumors by colonoscopy. We diagnosed it as a pathological complete response for biopsy specimen.     

Long-term results of spinal accessory nerve transfer to the suprascapular nerve in upper-type paralysis of brachial plexus injury

In the management of upper type of brachial plexus injury, reconstruction to restore shoulder function is accomplished by multiple nerve transfers. We used the accessory nerve to neurotize the suprascapular nerve in 12 patients (11 men, 1 woman) from 1989 to 2003. The average age at the time of operation was 28.1 years (range 16 to 53). The mean preoperative time was 3.6 months. The type of paralysis was C5-C6 type in four cases, C5-C7 type in five cases, and C5-C8 type in three cases. The average time of follow-up was 28.5 months. All the patients showed reinnervation of the supraspinatus and infraspinatus muscles that was confirmed by electromyogram. At the time of final followup, the average shoulder flexion was 70.4 degrees and abduction was 77.1 degrees. However, average shoulder external rotation was only 16.7 degrees. We compared the shoulder flexion and abduction in patients with or without paralysis of the serratus anterior muscle and found significantly better functional outcome in the latter group of patients. We, therefore, conclude that repair of long thoracic nerve is mandatory for achieving optimum shoulder function.     

Impact of age on outcomes of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in elderly patients with acute myeloid leukemia

Previous studies have repeatedly reported that increasing age is a significant risk factor for worse outcomes after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) among patients with acute myeloid leukemia (AML). However, more recent studies reported conflicting results regarding the association between age and outcomes in elderly patients. Therefore, we conducted a large‐scale, nationwide retrospective study to examine the impact of age on outcomes of allo‐HSCT with reduced intensity conditioning (RIC) for AML patients who were older than 50 years. Of the 757 patients, 89 patients (11.8%) were 50–54, 249 patients (32.9%) were 55–59, 301 patients (39.8%) were 60–64 and 118 patients (15.6%) were ≥65 years old. The 3‐year overall survival (OS) (47.8, 45.2, 37.9, and 36.6% for patients aged 50–54, 55–59, 60–64, and ≥65 years, respectively, P = 0.24) and nonrelapse mortality (NRM) (24.0, 22.8, 29.2, and 27.6% for patients aged 50–54, 55–59, 60–64, and ≥65 years, respectively, P = 0.49) were not significantly different among the four age groups. Multivariate analysis revealed that increased age had no significant effect on OS or NRM after adjusting for covariates. These results suggested that advanced patient age is not a contraindication for RIC allo‐HSCT in elderly AML patients. Am. J. Hematol. 91:302–307, 2016. © 2015 Wiley Periodicals, Inc.     

Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5–25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.     

Improved prognosis with additional medium‐dose VP16 to CY/TBI in allogeneic transplantation for high risk ALL in adults

Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium‐dose etoposide (VP16, 30‐40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30‐40 mg/kg) (N = 376) and CY/TBI (N = 1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014. Our analyses indicated that VP16/CY/TBI significantly reduced relapse compared with CY/TBI (risk ratio, 0.75; 95% confidence interval [CI], 0.56‐1.00; P = .05) with a corresponding improvement in leukemia‐free survival (hazard ratio [HR], 0.76; 95%CI, 0.62‐0.93; P = .01), particularly in patients transplanted at CR1 with advanced‐risk (positive minimal residual disease, presence of poor‐risk cytogenetics, or an initial elevated leukocyte count) (HR, 0.75; 95%CI, 0.56‐1.00; P = .05) or those transplanted beyond CR2 (HR, 0.58; 95%CI, 0.39‐0.88; P = .01). The addition of VP16 did not increase post‐transplant complications or nonrelapse mortality (HR, 0.88; 95%CI, 0.65‐1.18; P = .38). This study is the first to reveal the efficacy of the addition of medium‐dose VP16 to CY/TBI in high‐risk ALL. To establish new myeloablative conditioning regimens including VP16, a large‐scale prospective study is necessary.