Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by chronic, complement-mediated hemolysis, frequently leading to debilitating clinical symptoms and life-threatening complications such as thromboembolism (TE). A retrospective analysis was performed on 301 patients from the South Korean National PNH Registry to describe disease burden and identify TE-associated risk factors. TE was identified in 18 % of patients and was associated with increased risk for mortality [odds ratio (OR), 6.85; P < 0.001]. A multivariate analysis showed that PNH patients with elevated hemolysis [lactate dehydrogenase (LDH) levels ≥1.5 times the upper limit of normal (ULN)] at diagnosis were at significantly higher risk for TE than patients with LDH <1.5 × ULN (OR 7.0; P = 0.013). The combination of LDH ≥1.5 × ULN with the clinical symptoms of abdominal pain, chest pain, dyspnea, or hemoglobinuria was associated with a greater increased risk for TE than elevated hemolysis or clinical symptoms alone. Continuous monitoring of these risk factors is critical for identifying PNH patients at risk for morbidities and mortality and allowing early intervention.

Key Points• Nilotinib plus multiagent chemotherapy was feasible and showed a comparable outcome to previous results with imatinib for Ph-pos ALL.• The achievement of deep MR with nilotinib at postremission correlated well with the clinical outcomes for Ph-pos ALL.We investigated the effects of nilotinib plus multiagent chemotherapy, followed by consolidation/maintenance or allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with newly diagnosed Philadelphia-positive (Ph-pos) acute lymphoblastic leukemia (ALL). Study subjects received induction treatment that comprised concurrent vincristine, daunorubicin, prednisolone, and nilotinib. After achieving complete hematologic remission (HCR), subjects received either 5 courses of consolidation, followed by 2-year maintenance with nilotinib, or allo-HCT. Minimal residual disease (MRD) was assessed at HCR, and every 3 months thereafter. The molecular responses (MRs) were defined as MR3 for BCR-ABL1/G6PDH ratios £10 23 and MR5 for ratios <10 25. Ninety evaluable subjects, ages 17 to 71 years, were enrolled in 17 centers. The HCR rate was 91%; 57 subjects received allo-HCT. The cumulative MR5 rate was 94%; the 2-year hematologic relapse-free survival (HRFS) rate was 72% for 82 subjects that achieved HCR, and the 2-year overall survival rate was 72%. Subjects that failed to achieve MR3 or MR5 were 9.1 times (P 5 .004) or 6.3 times (P 5 .001) more prone to hematologic relapse, respectively, than those that achieved MR3 or MR5. MRD statuses just before allo-HCT and at 3 months after allo-HCT were predictive of 2-year HRFS. Adverse events occurred mainly during induction, and most were reversible with dose reduction or transient interruption of nilotinib. The combination of nilotinib with high-dose cytotoxic drugs was feasible, and it effectively achieved high cumulative complete molecular remission and HRFS rates. The MRD status at early postremission time was predictive of the HRFS. This trial was registered at www.clinicaltrials.gov as #NCT00844298. (Blood. 2015;126(6):746-756)

The objective of this study was to investigate whether metabolic tumor volume (MTV) by positron emission tomography (PET) can be a potential prognostic tool when compared with Ann Arbor stage, in stages II and III nodal diffuse large B cell lymphoma (DLBCL). We evaluated 169 patients with nodal stages II and III DLBCL who underwent measurements with PET prior to rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). Cutoff point of MTV was measured using the receiver operating characteristic (ROC) curve. During a median period of 36 months, stage II was 59.2% and III was 40.8%. Using the ROC curve, the MTV of 220 cm3 was the cutoff value. The low MTV group (<220 cm3) had longer progression-free survival (PFS) and overall survival (OS), compared with the high MTV group (≥220 cm3) (p < 0.001, p < 0.001). Stage II patients had longer survival than those in stage III (PFS, p = 0.011; OS, p = 0.001). The high MTV group had lower PFS and OS patterns, regardless of stage, compared with the low MTV group (p < 0.001, p < 0.001). Multivariate analysis revealed an association of the high MTV group with lower PFS and OS (PFS, hazard ratio (HR) = 5.300, p < 0.001; OS, HR = 7.009, p < 0.001), but not stage III (PFS, p = 0.187; OS, p = 0.054). Assessment of MTV by PET had more potential predictive power than Ann Arbor stage in the patients that received R-CHOP.

The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML.

Primary gastrointestinal (PGI) diffuse large B cell lymphoma (DLBCL) is a relatively common disease. Recent studies indicate that measurement of maximum standardized uptake value (SUV max ) on pretreatment for 18 F-fluorodeoxyglucose PET is an important prognostic factor in PGI DLBCL. However, there is still an association between initial tumor burden and prognosis. Thus, in the present study, we investigated whether tumor volume by PET could have a potential prognostic value to predict the outcome. From 2006From to 2009 Stage I E ⁄ II E PGI DLBCL patients were enrolled in the study. One hundred and five patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP) only, whereas 60 patients underwent surgery plus R-CHOP. Metabolic tumor volume (MTV) was defined initial tumor burden as target GI lesion above SUV, 2.5 by PET as a contouring border. Over a median follow-up period of 36.6 months, receiver operating characteristic (ROC) analysis indicated that the best cutoff values for MTV and SUV max were 160.1 cm 3 and 12.0, respectively. The estimated area under the ROC curve was higher for MTV than SUV max . Thus, MTV was a better predictor for survival than SUV max . In patients with a low MTV (<160.1 cm 3 ), there were no significant differences in survival between patients undergoing R-CHOP alone and surgery plus R-CHOP (P = 0.347 for progressionfree survival [PFS]; P = 0.148 for overall survival [OS]). Conversely, in patients with a high MTV (>160.1 cm 3 ), survival was longer in those who underwent surgery plus R-CHOP than in those treated with R-CHOP alone (P < 0.001 for PFS; P < 0.001 for OS). Multivariate analysis revealed that high MTV is an independent factor for predicting survival. Even in the era of rituximab, treatment of PGI DLBCL is not easy in patients with a high MTV. (Cancer Sci 2012; 103: 477-482) T he gastrointestinal (GI) tract is the most commonly involved extranodal site in primary non-Hodgkin's lymphoma (NHL), representing 10-15% of all cases of NHL and 30-40% of all extranodal sites.(1) The most commonly involved site is the stomach (60-70%), followed by the small bowel, ileum, cecum, colon and rectum. Thus, diffuse large B cell lymphoma (DLBCL) is one of the most common primary GI (PGI) lymphomas. (2,3)