Chieh-Lin Jerry Teng

Maintenance therapy with dasatinib after allogeneic hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia

cytogenetic abnormalities in adult acute lymphoblastic leu-kemia (ALL) [1]. Ph + ALL outcomes are usually dismalbut have been improving since tyrosine kinase inhibitorsbecome part of the treatment protocol [2]. Nonetheless,allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the standard treatment for Ph + ALL [3].A study by Caocci and colleagues [4] suggested that dasa-tinib is highly effective in preventing Ph + ALL relapse afterboth auto- and allo-HSCT. However, our preliminary datacould not fully support this conclusion.A total of six consecutive Ph + ALL adult patients whoreceived allo-HSCTand dasatinib maintenance therapy (100mg per day for 1 year) between November 2009 andOctober 2012 were retrospectively reviewed. All sixpatients achieved complete hematological remission beforeallo-HSCT. Examination to identify any bone marrow min-imal residual diseases (MRD) was routinely conductedbefore and 30, 60, and 180 days after allo-HSCT by usingmultidimensional flow cytometry [5] and quantitative poly-merase chain reaction bcr-abl transcript detection [6].Patient outcomes and graft-versus-host diseases (GVHD)were also analyzed. This study was approved by theInstitutional Review Board of Taichung Veterans GeneralHospital.Patients’ clinical characteristics are summarized inTable 1. Briefly, our study cohort comprised three menand three women with a median age of 44 years (range,28–65). The average follow-up time was 387 days (range,91–734). All patients were diagnosed with precursor BALL, except patient 2 who was diagnosed with ALL withmyeloid aberrancy. MRD was detected by flow cytometry inpatients 2, 3, and 6 before allo-HSCT but eventually dis-appeared in patients 2 and 3 by day 90; molecular MRDyielded similar results (Table 1).In terms of patient outcomes, disease relapse occurredin three of the six patients (patients 2, 4, and 5); allrelapses were extramedullary. Bcr-abl in bone marrowspecimens from patients 4 and 5 (but not from patient2) were analyzed when the extramedullary relapse was diag-nosed; neither wild-type nor mutated bcr-abl could bedetected. Extramedullary relapse occurred over the spi-nal cord in patient 2; in patient 5, extramedullary re-lapse occurred over the spleen. In patient 4, relapseoccurred over the liver, and bcr-abl could not be detected inthe hepatic lesion, suggesting that clonal evolution might beoneofthemechanismsresponsibleforextramedullaryrelapsein Ph + ALL patients treated with allo-HSCT and dasatinibmaintenance therapy.None of our study cohort had acute GVHD more severethan grade 2. In addition, chronic GVHD did not occur inany of these six patients, supporting the theory that mainte-nance dasatinib is effective as chronic GVHD prophylaxis[7]. In terms of adverse effects from dasatinib, only two of

Early Colonoscopy Confers Survival Benefits on Colon Cancer Patients with Pre-Existing Iron Deficiency Anemia: A Nationwide Population-Based Study

This study aimed to examine the prognostic significance of pre-existing iron deficiency anemia (IDA) and the benefits of early colonoscopy in patients with colon cancer, since these have not been clearly established to date. Using the Taiwanese National Health Insurance Research Database, we retrieved and retrospectively reviewed the records of patients aged ≥55 years who were diagnosed with colon cancer between 2000 and 2005. The patient cohort was divided into two groups: patients with (n = 1,260) or without (n = 15,912) an IDA diagnosis during ≤18 months preceding the date of colon cancer diagnosis. We found that diabetes (27.9% vs. 20.3%, p<0.0001), cardiovascular disease (61.6% vs. 54.7%, p<0.001), and chronic kidney disease (4.6% vs. 2.2%, p<0.0001) were more common among patients with IDA than among those without IDA. The median overall survival times for patients with IDA and those without IDA were 4.6 and 5.7 years, respectively (p = 0.002). Patients who underwent colonoscopy ≤30 days, 31–90, and ≥91 days after IDA diagnosis showed median overall survival times of 5.79, 4.43, and 4.04 years, respectively (p = 0.003). Delayed colonoscopy was an independent factor associated with poor overall survival (adjusted hazard ratio, 1.28; 95% confidence interval, 1.07–1.53; p = 0.01). In conclusion, colon cancer patients with IDA were more likely to experience comorbidities than were those without IDA. Pre-existing IDA was a poor prognostic factor in adult men and postmenopausal women who had colon cancer. Early colonoscopy could improve overall survival possibly by facilitating early diagnosis and treatment.

Optimal Sequence of Irinotecan and Oxaliplatin-Based Regimens in Metastatic Colorectal Cancer: A Population-Based Observational Study

The optimal sequence of irinotecan and oxaliplatin-based regimens for metastatic colorectal cancer remains unclear. We conducted a population-based observational study by retrospectively reviewing records from Taiwan’s National Health Insurance Research Database to explore this issue. Patients aged ≥20 years with metastatic colorectal cancer newly diagnosed between 2004 and 2008 (n = 9490) were enrolled in current study. Among these 9490 patients, 3895 patients (41.04%) did not receive any chemotherapy within the first three months after catastrophic illness registration. Patients who received best supportive care were older and had higher Charlson comorbidity indexes and incidences of comorbidities than those who received irinotecan-based regimens, oxaliplatin-based regimens, and 5-fluorouracil/capecitabine alone. Patients who received irinotecan followed by oxaliplatin-based regimens and those who received the reverse sequence were further stratified into arm A (n = 542) and arm B (n = 1156), respectively. The median first time to next treatment was not significantly different between arm A and arm B (210 days vs. 196 days; p = 0.17). However, the median second time to next treatment was longer in arm A than in arm B (155 days vs. 123 days; p = 0.006), which translated into a better overall survival (487 days vs. 454 days; p = 0.02). The crossover rate was higher in arm A than in arm B (47.84% vs. 41.61%; p<0.001). Multivariate Cox regression analyses showed that overall survival was comparable between the two chemotherapy sequences (p = 0.27). Our study suggested that irinotecan followed by oxaliplatin-based regimens might be a better chemotherapy treatment option for metastatic colorectal cancer than the reverse sequence given the higher crossover rate and potential overall survival benefit.

Increased risk of incident nasopharyngeal carcinoma with exposure to air pollution

Background Nasopharyngeal carcinoma (NPC) is a race-specific malignancy. The nasal cavity is the main entry point for air pollutants or poisonous gases into the human body. However, the risk of NPC in populations exposed to air pollution remains unknown. Methods We combined data from the Taiwan Air Quality Monitoring Database (TAQMD) and the Longitudinal Health Insurance Database (LHID) to assess the risk of NPC in a population exposed to air pollution. Results Multivariate analysis revealed positive trends for the association between the risk of NPC and exposure to air pollution. After adjusting for potential covariates, the risk of developing NPC increased with the increase in nitrogen dioxide (NO2) and fine particulate matter (PM2.5) exposure concentrations from 1.39 to 2.28 and 2.01 to 1.97, respectively, compared to the risks at the lowest concentration levels. Conclusions We identified a significant risk of NPC in a population exposed to air pollution. However, this study had several limitations. Moreover, additional experimental and clinical studies on the associations between environmental factors and NPC risk are warranted.

Cytomegalovirus infection and treatment in allogeneic hematopoietic stem cell transplantation: a retrospective study from a single institution in an endemic area.

Objective: Although Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the risk factors for CMV reactivation and treatment failure in CMV endemic areas have remained unclear. This study investigated the risk factors for CMV reactivation among allo-HSCT recipients in an area where CMV is highly endemic. Materials and Methods: Medical records of 82 allo-HSCT recipients from a CMV endemic area were retrospectively reviewed. The patients were stratified into two groups: those with CMV reactivation (n=32) and those without CMV reactivation (n=50). We investigated possible variables associated with CMV reactivation and treatment failure. Results: Univariate analyses showed that non-remission disease status [hazard ratio (HR): 2.15; p=0.032] and ≥grade III acute graft-versus-host disease (GVHD) (HR: 3.07; p=0.002) were associated with CMV reactivation. Multivariate analysis further demonstrated that older age (HR: 1.03; p=0.029) and ≥grade III acute GVHD (HR: 2.98; p=0.012) were associated with CMV reactivation. Overall survival time seemed lower among patients with CMV reactivation than among patients without CMV reactivation, although the difference was not statistically significant (p=0.165). The absence of ≥grade III acute GVHD was associated with successful CMV treatment in the current study (odds ratio: 4.40; p=0.008). Conclusion: Prophylactic anti-CMV therapy might need to be considered for allo-HSCT recipients who have ≥grade III GVHD.

Application of peripherally inserted central catheter in acute myeloid leukaemia patients undergoing induction chemotherapy

&NA; Increasingly, peripherally inserted central catheters (PICC) are applied in patients with haematological malignancies. The feasibility and safety of PICC for induction chemotherapy in acute myeloid leukaemia (AML) remain unclear. Medical records of 89 newly diagnosed adult de novo AML patients, who achieved complete remission, were retrospectively reviewed (PICC group, n = 43; intravenous [IV] line group, n = 46). Patients’ clinical characteristics and the number of blind punctures for blood sampling were compared between these two groups, and risk factors associated with bacteraemia were identified by univariate analysis. Patients in the PICC group experienced significantly fewer blind punctures than those in the IV line group (3.3 ± 3.6 vs. 14.4 ± 6.0; p = .000); 20.9% of PICC patients had bacteraemia, compared with 23.9% in the IV line group (p = .803). Most patients (76.7%) removed their PICC because treatment was completed. PICC increased the quality of life in AML patients undergoing chemotherapy induction by reducing the number of blind blood punctures required. Bacteraemia in PICC patients was comparable to that in IV line patients. PICC is, therefore, a feasible and safe central venous device for use in AML patients.

Circulating hematopoietic progenitors and CD34+ cells predicted successful hematopoietic stem cell harvest in myeloma and lymphoma patients: experiences from a single institution

Background Previous studies have shown that the numbers of both circulating hematopoietic progenitor cell (HPC) and CD34+ cell are positively correlated with CD34+ cell harvest yield. However, the minimal numbers of both circulating HPCs and CD34+ cells required for performing an efficient hematopoietic stem cell (HSC) harvest in lymphoma and myeloma patients have not been defined in our institution. Patients and methods Medical records of 50 lymphoma and myeloma patients undergoing peripheral blood HSC harvest in our institution were retrospectively reviewed. The minimal and optimal HSC harvest yield required for the treatment was considered to be ≥2×106 CD34+ cells/kg and ≥5×106 CD34+ cells/kg, respectively. Results The minimally required or optimal HSC yield obtained was not influenced by age (≥60 years), sex, underlying malignancies, disease status, multiple rounds of chemotherapy, or history of radiotherapy. The numbers of both circulating HPC and CD34+ cell were higher in patients with minimally required HSC yields (P=0.000 for HPC and P=0.000 for CD34+ cell) and also in patients with optimal HSC yields (P=0.011 for HPC and P=0.006 for CD34+ cell). The cell count cutoff for obtaining minimally required HSC harvest was determined to be 20/mm3 for HPCs and 10/mm3 for CD34+ cells. Furthermore, the cell count cutoff for obtaining optimal HSC harvest was determined to be 60/mm3 for HPCs and 35/mm3 for CD34+ cells. Conclusion A total of 60/mm3 of HPCs and 35/mm3 of CD34+ cells in peripheral blood predicted optimal HSC harvest in lymphoma and myeloma patients.

Treatment of Adolescent and Young Adult Acute Lymphoblastic Leukemia with the Pediatric Protocol: Results from a Single Institution in Taiwan

Background: It remains unclear whether pediatric protocols provide a better outcome to adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) than adult protocols in Taiwan. Therefore, we conducted a case-control study to compare the outcome events, disease-free survival (DFS), and overall survival (OS) in Taiwanese AYA patients receiving either pediatric or adult ALL protocols. Methods: Twenty-three Taiwanese AYA patients with ALL were retrospectively reviewed: eight patients received the pediatric ALL protocol modified from the Taiwan Pediatric Oncology Group (mTPOG) regimen, and 15 were treated by using the Cancer and Leukemia Group B study 8811 (CALGB-8811) regimen. Results: The DFS rates for patients in the mTPOG and CALGB-8811 groups were 100% versus 33.3% (p = 0.016) at one year, and 100% versus 22.2% (p = 0.006) at two years, respectively. The OS rates for patients in mTPOG and CALGB-8811 groups were 100% versus 37.0% (p = 0.013) at one year, and 100% versus 22.2% (p = 0.003) at two years, respectively. Conclusions: Our results suggested that the pediatric mTPOG protocol provides AYA ALL patients a better DFS and OS than the adult CALGB-8811 protocol.

Positron Emission Tomography/Computed Tomography False Positivity for Xanthogranulomatous Inflammation in an Adolescent with Hodgkin's Lymphoma

Abstract Although positron emission tomography/computed tomography (PET/CT) is a sensitive tool for Hodgkins lymphoma (HL) staging and response evaluation, its role in early detection of disease relapse remains controversial. A high false positivity of routine PET/CT during follow-up may result in unnecessary treatment of HL patients who are in complete remission. Here we report a 15-year-old boy who had a false positive PET/CT result during his follow-up. Debulking surgery was performed for the suspicious lesion, which showed xanthogranulomatous inflammation, fibrosis, old hemorrhage and fibrous adhesion of thymic tissue and pleura, but no residual tumor cells. One year after the surgery, this patient remained well without any evidence of disease relapse. Our case shows that PET/CT could provide false positive imaging in HL patients who are in complete remission after treatment. Tissue biopsy remains the really necessary tool of confirming disease relapse in patients with HL.

Splenic irradiation-induced gastric variceal bleeding in a primary splenic diffuse large B-cell lymphoma patient: a rare complication successfully treated by splenectomy with short gastric vein ligation

Primary splenic diffuse large B-cell lymphoma (DLBCL) is a rare clinical condition, which is generally treated by six to eight cycles of chemotherapy involving a combination of rituximab and the cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) regimen. However, the treatment for chemorefractory primary splenic DLBCL remains controversial. Therapeutic splenic irradiation (SI) might be a reasonable and possibly the only treatment option with curative intention for patients with chemorefractory primary splenic DLBCL. However, the efficacy and safety of therapeutic SI are unclear. Herein, we present the case of a primary splenic DLBCL patient who was refractory to multiple chemotherapy regimens but achieved complete remission after administration of therapeutic SI. However, his condition was complicated with severe gastric variceal bleeding due to splenic venous thrombosis, which was successfully treated via splenectomy and short gastric vein ligation. On the basis of our findings, we concluded that the splenic venous thrombosis-induced gastric variceal bleeding was a rare but life-threatening adverse effect of the therapeutic SI administered for primary splenic DLBCL. Surgical intervention involving splenectomy and short gastric vein ligation is mandatory and should be performed as soon as possible for such patients.