Brentuximab vedotin plus AVD followed by involved-node radiotherapy in a patient with classic Hodgkin lymphoma following gray zone lymphoma after autologous stem-cell transplantation failure.

BACKGROUND: No consensus has been reached yet concerning treatment strategies for a sequential classic Hodgkin lymphoma (CHL) following gray zone lymphoma (GZL). Prognosis of GZL after a failed autologous hematopoietic stem-cell transplantation (auto-HCT) is poor and treatment strategy is very limited. As yet there are limited data showing clinical outcomes of brentuximab vedotin (BV) for GZL, especially for sequential CHL after GZL. CASE PRESENTATION: We report a case of CHL following primary refractory GZL after a failed auto-HCT and showed favorable response to first-line CHL-directed chemoradiotherapy consisting of BV plus doxorubicin, vinblastine, and dacarbazin (AVD) followed by irradiation. The sequential cases with an early evolution, whose diagnosis of second lymphoma was made within a year, have been recently reported very poor survival shorter than a year. Whether a sequential CHL following GZL should be treated as a primary or relapsed disease has not been clearly elucidated. Our patient showed favorable response to first-line CHL-directed chemoradiotherapy without allogenic hematopoietic stem-cell transplantation and has in continuous remission for 2 years. CONCLUSIONS: The management of our case could help for physicians to make better treatment decisions and provide insights for further exploration in future studies.

Efficacy and safety of modified BLd therapy for Japanese patients with transplant-ineligible multiple myeloma.

The BLd regimen, which is a triplet regimen of bortezomib (Bor), lenalidomide (Len), and dexamethasone (Dex), is effective against newly diagnosed multiple myeloma (NDMM). However, non-hematological toxicities, such as peripheral neuropathy (PN), often hamper long-term continuation of the regimen, particularly in older adult patients. In this study, we examined the efficacy and safety of the modified BLd regimen with reduced-intensity Bor and standard-dose Len. The chemotherapy regimen consisted of 1.3 mg/m2 Bor administered subcutaneously on days 1 and 8, 25 mg Len administered on days 1-14, and 20 mg Dex on days 1-2 and 8-9 of a 3 week cycle for 8 cycles, followed by a 4 week cycle of Dex (40 mg weekly). Among the 30 patients enrolled, 60.0% (95% CI 40.6-77.3) had a very good partial response or better, and the best overall response rate was 96.7% (95% CI 82.8-99.9). Eight patients (26.7%) achieved a complete response. Grade 3 or higher PN was not observed and hematological toxicity was the most common adverse event. The modified BLd regimen showed favorable efficacy with a manageable safety profile, which suggests it could be a treatment option for transplant-ineligible NDMM.

Retraction Note to: High-dose therapy and autologous stem cell transplantation for relapsed or high-risk diffuse large B-cell lymphoma: a nationwide survey.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s12185-020-03018-1.

Dasatinib-induced Reversible Demyelinating Peripheral Neuropathy and Successful Conversion to Nilotinib in Chronic Myelogenous Leukemia.

Dasatinib, a tyrosine kinase inhibitor, is commonly used in the treatment of chronic myelogenous leukemia. A rare side effect is peripheral neuropathy. A 54-year-old woman experienced gradually accelerated dysesthesia and hypoesthesia in her extremities, 2 months following treatment with dasatinib. Nerve conduction studies revealed a prolonged conduction velocity with temporal dispersion, indicating demyelinating peripheral neuropathy. After changing dasatinib to nilotinib, both her clinical symptoms and electrophysiological data gradually improved. We herein report the findings of this case with a review of the pertinent literature.

High-dose therapy and autologous stem cell transplantation for relapsed or high-risk diffuse large B-cell lymphoma: a nationwide survey.

To investigate the use of high-dose therapy and autologous stem cell transplantation (ASCT) for relapsed or high-risk diffuse large B-cell lymphoma (DLBCL) between 1990 and 2007, we conducted a nationwide survey using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Of the 1222 patients in the database, 576 (47%) received ASCT in first complete remission (CR1), 140 (12%) in first partial remission, 281 (23%) in sensitive relapse, 150 (12%) in resistant or sensitivity-unknown relapse, and 75 (6%) in primary refractory status. With a median follow-up of 22 months, the 2-year overall survival (OS) and progression-free survival rates were 71% and 68%, respectively. The cumulative incidences of 2-year non-relapse mortality and relapse/progression were 6% and 26%, respectively. Relapse/progression after ASCT in the rituximab era (2002-2007) was significantly lower than that in the pre-rituximab era (1990-2001; P < 0.001). Older age, male gender, poor performance status at ASCT, non-CR1 at ASCT, ASCT performed in 1990-2001, and LEED or MCEC regimen were adverse predictors of OS. Because ASCT for newly diagnosed high-risk DLBCL has not been performed recently, a registry database study to assess the impact of ASCT for relapsed or refractory DLBCL in the rituximab era is warranted.

Risk factors and timing of autologous stem cell transplantation for patients with peripheral T-cell lymphoma.

High-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) is an option for patients with peripheral T-cell lymphoma (PTCL); however, neither prospective nor retrospective studies support proceeding with ASCT upfront, and the timing of HDC-ASCT remains controversial. We retrospectively analyzed the risk factors for outcomes of 570 patients with PTCL, including PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL), who received ASCT for frontline consolidation (n = 98 and 75, respectively) or alternative therapies after either relapse (n = 112 and 75) or primary induction failure (PIF; n = 127 and 83) between 2000 and 2015. Significant risk factors for overall survival (OS) after upfront ASCT were a ≥ 2 prognostic index for T-cell lymphoma (P < 0.001) and partial response (PR) at ASCT (P = 0.041) in PTCL-NOS patients, and > 60 years of age (P = 0.0028) and PR at ASCT (P = 0.0013) in AITL patients. Performance status of ≥ 2 at ASCT (P < 0.001), receiving ≥ 3 regimens before ASCT (P = 0.018), and PR at ASCT (P = 0.018) in PTCL-NOS patients and > 60 years of age at ASCT (P = 0.0077) in AITL patients were risk factors for OS after ASCT with a chemosensitive PIF status. Strategies that carefully select PTCL patients may allow identification of individuals suitable for ASCT.

Immunophenotypic analysis of adult patients with T-cell lymphoblastic lymphoma treated with hyper-CVAD.

OBJECTIVES: Immunophenotype is an important prognostic factor for childhood and adult T-cell acute lymphoblastic leukemia. However, immunophenotypic data from adult patients with T-cell lymphoblastic lymphoma (T-LBL) are scarcely available. METHODS: Subjects were unselected adult patients with T-LBL who were treated with intensive chemotherapy. Immunophenotyping of tumor cells was performed according to standard techniques. RESULTS: A total of eight patients with a median age of 31 years were analyzed who received hyper-CVAD treatment for LBL. Immunophenotypic analysis showed that the most common tumor type was cortical T-cell type [early T (n = 2), cortical T (n = 4), and medullary T (n = 2)]. Two patients diagnosed with early T-cell type had early disease progression. CONCLUSIONS: Assessment of T-cell differentiation stages in malignant T lymphoblasts would be important in choosing treatment strategies for adult patients with T-LBL.

Anti-CCR4 Monoclonal Antibody Mogamulizumab Followed by the GDP (Gemcitabine, Dexamethasone and Cisplatin) Regimen in Primary Refractory Angioimmunoblastic T-Cell Lymphoma.

There are few effective options for salvage therapy in elderly patients with relapsed or refractory angioimmunoblastic T-cell lymphoma (AITL). The anti-CCR4 antibody mogamulizumab works via antibody-dependent cytotoxic activity, reduces regulatory T cells, and evokes antitumor immunity in cancer patients. We report a 78-year-old patient with refractory AITL receiving a new immunochemotherapy consisting of sequential mogamulizumab administration followed by the GDP (gemcitabine, dexamethasone and cisplatin) regimen. A favorable consolidative effect of the GDP regimen could be observed in the patient who had partial remission after administration of mogamulizumab monotherapy. The regimen showed an acceptable toxicity profile without serious autoimmunity and an expected treatment response for the elderly patient with primary refractory AITL. This clinical case is the first report of salvage chemotherapy including mogamulizumab for primary refractory AITL described in the literature.

Prediction of high risk for death in patients with follicular lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in first-line chemotherapy.

Risk stratification of patients with relapsed and refractory follicular lymphoma (FL) remains challenging. Recently, much attention has been paid to the impact of early progression of disease within 2 years of diagnosis (early POD) on subsequent survival. The aim of this study was to clarify the clinical features and prognostic factors of patients with FL who experienced early POD. Data were available for 94 patients diagnosed with FL (clinical stage II-IV) who had received immunochemotherapy. Early POD was seen in 20 % of these patients. The Cox proportional hazards model showed worse overall survival (OS) in the patients with early POD compared with those without early POD (5-year OS rates 48 % vs. 96 %, P < 0.0001). In multivariate analysis, early POD (P = 0.003) and poor performance status (P = 0.006) remained a significant factor for subsequent OS. In Follicular Lymphoma International Prognostic Index (FLIPI)- and Follicular Lymphoma International Prognostic Index-2 (FLIPI2)-adjusted Cox regression analysis, early POD was associated with markedly reduced OS with a hazard ratio of 11.2 [95 % confidence interval (CI) 3.13-40.3, P < 0.001] and 13.5 (95 % CI 3.22-56.3, P < 0.003), respectively. Among patients who had early POD, high levels of serum lactate dehydrogenase (LDH) both at the time of initial diagnosis and first progression could be associated with worse survival (2-year OS rates 33 vs. 92 %, P < 0.0001). Evaluation of LDH levels at the time of initial diagnosis and first progression may be important to define patients who were associated with worse prognosis. Risk stratification of patients with early POD could lead to improved clinical outcomes for FL patients. Further research is needed to investigate its value for decision making.

The role of hematopoietic stem cell transplantation for relapsed and refractory Hodgkin lymphoma.

The optimal treatment strategy with the use of hematopoietic stem cell transplantation (HSCT) for relapsed and refractory Hodgkin lymphoma (HL) remains unclear. We performed a retrospective analysis using registry data from the Japanese Society for Hematopoietic Cell Transplantation. Adult patients with HL who underwent a first autologous or a first allogeneic HSCT between 2002 and 2009 were included. Patients who underwent HSCT in first complete remission (CR) were excluded. Autologous and allogeneic HSCT were performed in 298 and 122 patients, respectively. For autologous HSCT, overall survival at 3 years (3yOS) was 70%, and sex, age, disease status, and performance status (PS) at HSCT were prognostic factors. OS was favorable even in patients who underwent autologous HSCT in disease status other than CR. For allogeneic HSCT, 3yOS was 43%, and sex and PS at HSCT were prognostic factors. Disease status at HSCT, previous autologous HSCT, and conditioning intensity did not affect OS. Moreover, graft-versus-host disease did not affect progression-free survival or relapse/progression rate. A first allogeneic HSCT without a previous autologous HSCT was performed in 40 patients. 3yOS was 45%, and was significantly inferior to that in patients who underwent their first autologous HSCT. This result was retained after the correction by the different patient characteristics according to the type of HSCT. In conclusion, autologous HSCT is effective in prolonging survival in patients with relapsed and refractory HL. Allogeneic HSCT might be beneficial even to relapsed HL after autologous HSCT, although establishing the role of allogeneic HSCT remains a challenge.

Interstitial pneumonia after autologous hematopoietic stem cell transplantation in B-cell non-hodgkin lymphoma.

INTRODUCTION: During the past decade, interstitial pneumonia (IP) is one of the newly recognized adverse events regarding rituximab therapy. However, disease characteristics of IP after autologous hematopoietic stem cell transplantation (ASCT) have not been well-described since the introduction of rituximab. PATIENTS AND METHODS: We retrospectively analyzed 103 patients with B-cell non-Hodgkin lymphoma undergoing ASCT. A propensity scoring system was applied in our analysis to eliminate potential confounding factors of covariates. RESULTS: The total number of patients who developed IP was nine. Five patients developed IP among 57 patients previously treated with rituximab, and four patients developed IP among 46 who were rituximab-naïve. Cumulative incidence of IP was 7.8% at 1 year. Among the patients using rituximab, one patient had IP during the peri-engraftment period (cytomegalovirus infection), three patients had IP between 3 and 12 months (Pneumocystis pneumonia [PCP, n = 1] and unknown cause [n = 2]), and the other one patient had IP 3.3 years after ASCT (unknown cause). Four patients in the rituximab-naïve group developed IP between 3 and 12 months (PCP [n = 1] and unknown cause [n = 3]). All nine patients had symptomatic episodes before IP, three of which died of IP or secondary infections. Patients receiving a total body irradiation conditioning regimen had a higher risk of IP (odds ratio = 3.6, P < .001), whereas the incidence was not affected by rituximab usage (P = .85, Log-rank test). CONCLUSION: This study shows that the rituximab usage was not identified as a risk factor of IP and that total body irradiation was the only independent risk factor for IP. Close monitoring is encouraged when symptomatic unexplained episodes are identified during follow-up examinations after ASCT.

Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: analyses with competing risk regression model.

Central nervous system (CNS) relapse is a challenging complication in patients with diffuse large B-cell lymphoma (DLBCL). Thus, identification of the high-risk population, in whom prophylactic treatment may play a significant role, is critical. We calculated the incidence of CNS relapse and evaluated the risk factors for CNS relapse using competing risk regression analysis. A total of 386 patients who received CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) with (n = 203) or without (n = 183) rituximab were analyzed. The 5-year cumulative incidence of CNS relapse was 6.7%. Multivariate analysis identified three independent risk factors: bulky disease (subhazard ratio [SHR] 3.34, 95% confidence interval [1.45-7.66], p = 0.004), absolute lymphocyte count <1.0 × 10(9)/L (SHR 2.38 [1.05-5.39], p = 0.037) and extranodal involvement (SHR 2.90 [1.01-8.33], p = 0.047). Patients with three risk factors represented 6% of patients, in whom the 5-year cumulative incidence was 26%. Larger scale studies are needed to validate our results. A better management strategy in patients with high-risk disease is critically needed.

High maximum standard uptake value (SUVmax) on PET scan is associated with shorter survival in patients with diffuse large B cell lymphoma.

FDG-PET scan plays an important role in response assessment in diffuse large B cell lymphoma (DLBCL). In this study, we evaluated the prognostic value of maximum standard uptake (SUVmax) on pretreatment PET scan in DLBCL. Among 169 patients with DLBCL newly diagnosed and treated with R-CHOP between 2003 and 2008, 110 patients who had undergone pretreatment PET scan in single institute using an identical protocol were reviewed and analyzed. SUVmax at the predominant lesion on PET scan and other patient characteristics were evaluated for their association with complete response (CR) rate, overall survival (OS) and progression-free survival (PFS). The median SUVmax was 18.1 (2.0-36.4). There was no significant association between high SUV and other characteristics with the exception of PS ≥ 2 and Ki-67. Multivariate analysis revealed the independent association between high SUVmax and lower CR rate. The 3-year PFS rates in patients with SUV < 30 and those with SUV ≥ 30 were 78 and 51%, respectively (p = 0.06). The 3-year OS rates were 86 and 71%, respectively (p = 0.03). Multivariate analysis revealed that high SUVmax is a significant poor prognostic factor for both PFS and OS, independent of IPI. We showed the important prognostic value of pretreatment SUVmax of PET scan in DLBCL.

Primary gastric diffuse large B-cell Lymphoma (DLBCL): analyses of prognostic factors and value of pretreatment FDG-PET scan.

OBJECTIVES: We report a single institution experience with gastric diffuse large B-cell lymphoma (DLBCL) in an attempt to evaluate the roles of different treatment modalities, to assess the value of pretreatment positron emission tomography (PET) scan, and to identify potential prognostic factors. METHODS: Among 384 patients diagnosed with DLBCL between 1995 and 2008, 75 patients had primary gastric DLBCL and were reviewed and analyzed. RESULTS: The median age was 66. International prognostic index (IPI) risk was low in 52%, low-intermediate in 23%, high-intermediate in 9%, and high in 16%. Pretreatment PET scan was highly sensitive in detecting gastric lesions except stage I gastric DLBCL without detectable mass by CT or gastroscopy. As a general rule, patients with limited-stage disease were treated with three times of CHOP (with or without rituximab) and radiotherapy, and those with advanced-stage disease were treated with eight cycles of CHOP (with or without rituximab), and radiotherapy was given to residual diseases after chemotherapy. Three-year overall survival (OS) rate was 78%. Multivariate analysis revealed that low albumin, hemoglobin <12.0 g/dL, and treatment without rituximab were independently associated with shorter OS. Low albumin, hemoglobin <12.0 g/dL,and advanced stage were independently associated with shorter progression-free survival. CONCLUSION: We showed the survival benefit of rituximab and potential prognostic value of pretreatment hemoglobin and serum albumin levels in gastric DLBCL.