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A three-drug combination of cyclophosphamide, bortezomib, and dexamethasone (CVD) shows significant efficacy and manageable toxicity as induction therapy in patients with multiple myeloma (MM).In this phase II study, we enrolled 45 patients who achieved a very good partial response (VGPR) or PR after autologous stem cell transplantation (ASCT) and evaluated the efficacy and toxicity of CVD consolidation. CVD consolidation comprised three cycles of cyclophosphamide 300 mg/m2 orally on days 1, 8, and 15, and bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, 15, and 22, along with dexamethasone 20 mg orally or intravenously on days 1 and 2, 8 and 9, 15 and 16, and 22 and 23.At enrollment, 39 (86.7%) patients showed VGPR, and nine (13.3%) presented with PR. Nineteen (45.2%) patients achieved a complete response (CR) or better as their best response after the end of consolidation. Overall, 22 (52.4%) of 42 patients experienced an improved response status with CVD consolidation. Three-year overall survival and progression-free survival rates were 89.0% and 42.7%, respectively. The most common non-hematologic toxicities were peripheral neuropathy and infection (20.5%), with no grade ≥ 3 neuropathy observed.These results showed that CVD consolidation therapy improved the response with reasonable toxicity in patients with residual disease after ASCT. This trial was registered with the Clinical Research Information Service, Republic of Korea (KCT0001327).

Peripheral T-cell lymphoma (PTCL) is an aggressive and heterogenous T-cell lymphoid malignancy. The prognostic value of C-reactive protein-to-albumin ratio (CAR) has never been assessed in PTCL.This study retrospectively reviewed the medical records of 76 patients diagnosed with various subtypes of PTCL. A CAR cutoff value of 0.794 was determined, and clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), were compared between the high ( 0.794) and low (≤ 0.794) CAR groups.After induction therapy, complete response was achieved in 8 (32.0%) and 39 patients (76.5%) in the high and low CAR groups, respectively. During the median follow-up of 57.5 months, the high CAR group had significantly worse 5-year PFS and 5-year OS rates. Even with adjustment for the International Prognostic Index (≥ 3), Prognostic Index for PTCL-unspecified (≥ 3), and T cell score (≥ 2), high CAR remained a significant prognostic factor for PFS (hazard ratio [HR]: 4.01, 95% confidence interval [CI] 2.04-7.86, p 0.001) and OS (HR: 2.97, 95% CI: 1.33-6.64, p = 0.008).CAR may play a complementary role in predicting prognosis in patients with PTCL, considering its simplicity, objectivity, and easy accessibility.

PurposeImmune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis. Materials and MethodsIn this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated. ResultsPneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031).ConclusionSequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients.

Background: Peripheral T cell lymphoma (PTCL) is a heterogeneous entity with poor survival. We evaluated the neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and platelet count as new prognostic factors for PTCL. Patients and Methods: We retrospectively analyzed 77 patients with PTCL initially treated with anthracycline-based chemotherapy. Survival curves were compared between groups with different initial NLR (iNLR), end-point NLR (eNLR), initial ALC, and platelet counts. Cox regression was used to analyze the risk factor for survival. Results: Patients with a higher eNLR (≥3), lymphopenia (< 1,000/μL), and thrombocytopenia (< 150 K/μL) had an inferior progression-free survival (PFS) and overall survival (OS) compared to their counterparts, while a higher iNLR (≥3) was predictive of a shorter OS but not PFS. Among these, thrombocytopenia was an independent poor prognostic factor for both PFS and OS, with a hazard ratio of 2.42 (p = 0.012) for PFS and 4.21 (p = 0.006) for OS. The presence of thrombocytopenia further stratified patients with a worse prognosis within overlapping risk-groups by the prognostic index for PTCL. Conclusions: Our study showed that thrombocytopenia at diagnosis was an independent prognostic factor for survival in patients with PTCL.

The C-reactive protein-to-albumin ratio (CAR) has not been assessed in diffuse large B cell lymphoma (DLBCL, the most common non-Hodgkin lymphoma). This retrospective study evaluated the prognostic value of CAR in 186 DLBCL patients. A CAR value of 0.158 was selected as the most discriminative cut-off for identifying patients with high CAR values (73/141 patients, 51.8%). During a median follow-up of 32.5 months, the high CAR group had significantly poorer complete response to induction therapy (64.4% vs. 92.6%; p 0.158 also showed worse 3-year OS (47.9% vs. 87.2%, p = 0.0035) and 3-year PFS (36.1% vs. 82.1%, p = 0.0011). A high CAR remained significantly associated with poor outcomes for > 60-year-old patients (OS: p = 0.0038, PFS: p = 0.0015) and younger patients (OS: p = 0.0041, PFS: p = 0.0044). Among older patients, a high CAR value also predicted non-relapse mortality (p = 0.035). Therefore, the CAR might complement the International Prognostic Index in DLBCL cases.

Total body irradiation (TBI) is included in the conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT), with unique advantages such as uniform distribution over the whole body and decreased exposure to cytotoxic chemotherapeutic agents. For individuals who lack matched sibling or matched unrelated donors, the use of haploidentical donors has been increasing despite challenges such as graft rejection and graft-versus-host disease (GVHD). Although a limited number of studies have been performed to assess the clinical role of TBI in haploidentical HSCT, TBI-based conditioning showed comparable results in terms of survival outcomes, rate of relapse, and GVHD in diverse hematologic malignancies such as leukemia, lymphoma, and multiple myeloma. Advances in supportive care, along with recent technical improvements such as restriction of maximum tolerated dose, appropriate fractionation, and organ shielding, help to overcome diverse adverse events related to TBI. Post-transplantation cyclophosphamide was used in most studies to reduce the risk of GVHD. Additionally, it was found that post-transplantation rituximab may improve outcomes in TBI-based haploidentical HSCT, especially in patients with B-cell lymphoma. Along with the advances of techniques and strategies, the expansion of age restriction would be another important issue for TBI-based haploidentical HSCT considering the current tendency toward increasing age limitation and lack of matched donors. This review article summarizes the current use and future perspectives of TBI in haploidentical HSCT., Graphical Abstract

// Jongheon Jung 1, 2 , Hyewon Lee 1, 3 , Tak Yun 1, 4 , Eunyoung Lee 1, 3 , Hae Moon 1 , Jungnam Joo 5 , Weon Seo Park 6 , Mihong Choi 7 , Jeong-Ok Lee 8 , Jong Seok Lee 8 and Hyeon-Seok Eom 1, 2, 3 1 Department of Internal Medicine, National Cancer Center, Goyang, Korea 2 Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea 3 Center for Hematologic Malignancy, National Cancer Center, Goyang, Korea 4 Rare Cancers Clinic, Center for Specific Organs Cancer, National Cancer Center, Goyang, Korea 5 Biometrics Research Branch, Research Institute, National Cancer Center, Goyang, Korea 6 Department of Pathology, National Cancer Center, Goyang, Korea 7 Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea 8 Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea Correspondence to: Hyeon-Seok Eom, email: hseom@ncc.re.kr Keywords: primary central nervous system lymphoma, neutrophil-to-lymphocyte ratio, prognosis Received: April 19, 2017 Accepted: July 16, 2017 Published: August 24, 2017 ABSTRACT Neutrophil-to-lymphocyte ratio (NLR) is one of the parameters of a complete blood cell count (CBC) test and has been reported to be an easily accessible prognostic marker in aggressive cancer, including non-Hodgkin lymphoma (NHL). Primary central nervous system lymphoma (PCNSL) is an extranodal NHL with highly aggressive features. However, the importance of the NLR has never been assessed in PCNSL. This retrospective study enrolled 62 biopsy-proven patients whose baseline NLR was available, and reviewed their medical records to compare both high (≥2.0) and low NLR (

Introduction Diffuse large B cell lymphoma (DLBCL) is the most common highly aggressive non-Hodgkin lymphoma (NHL) worldwide. The International Prognostic Index (IPI) has been established as a useful prognostic marker, and there have been some proposed markers which could reflect tumor microenvironment including neutrophil, lymphocyte, platelet, serum globulin, ferritin and serum free light chain. C-reactive protein (CRP) is one of the commonly used inflammatory markers, and its clinical relevance has been suggested recently in various malignancies. Serum albumin is a representative marker for nutritional status, and previous studies have presented that hypoalbuminemia might be an indicator of cancer-related inflammation as well. In this point of view, C-reactive-to-albumin ratio (CAR) has been suggested as one of easily-accessible parameters which could be a robust prognostic marker in diverse malignancies such as lung cancer, gastric cancer and colorectal cancer. However, its clinical value has not been assessed in hematologic malignancies. In this study, we evaluated the prognostic effect of CAR in DLBCL. Methods This retrospective study included 186 patients who were histologically diagnosed with DLBCL and treated with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) between 2006 and 2018 at National Cancer Center, Korea. One hundred forty one cases were identified whose baseline laboratory values including CRP and albumin were available, and then the medical records were reviewed. To define the appropriate cutoff value of CAR in patients with DLBCL, cutoff finder method was applied which had been suggested by Budczies et al., and the most discriminative point was designated by the value of 0.158. Clinical characteristics and outcomes including response rate, overall survival (OS) and progression-free survival (PFS) were investigated between high and low CAR group. Additionally, the clinical value of CAR was compared to the components of IPI for DLBCL as well. Results Of all patients, 73 (51.8%) were classified as high CAR group. Male was 42 (57.5%) in high CAR group and 37 (54.4%) in low CAR group. In terms of IPI, 21 (28.8%) were classified into high IPI (score of 4 or 5) in high CAR group - 6 (8.8%) in low CAR group in comparison. Hans criteria was applied to discriminate germinal center B-cell (GCB) subtype to non-GCB subtype by immunohistochemistry and after 12 patients removed due to missing GCB status, 56 (84.8%) in high CAR group was sorted to non-GCB type - 46 (73.0%) in low CAR group to be compared. The high CAR group showed significantly worse complete response (CR) rates to induction R-CHOP therapy (64.4% vs. 92.6%; p60), stage (III, IV), lactate dehydrogenase (LDH) (>upper normal limit), Eastern Cooperative Oncology Group (ECOG) performance status (>1) and the number of extranodal involvement (>1), high CAR showed statistically significant results for both 5-year OS (HR 4.71, 95% CI 1.175-18.892; p=0.029) and 5-year PFS (HR 2.66, 95% CI 1.122-6.289; p=0.026) (Table 1). Conclusions In conclusion, CAR might play an additional role to IPI in prognostication of patients with DLBCL considering the fact that it is simple, objective and easy to obtain. Disclosures No relevant conflicts of interest to declare.