Cyclophosphamide, Vincristine, Prednisone Research Articles

Clinical analysis of cytomegalovirus infection-associated hemophagocytic lymphohistiocytosis in five patients without underlying diseases

The clinical data of five patients [one male and four female; median age: 31 (21-65) years] with cytomegalovirus (CMV)-induced hemophagocytic lymphohistiocytosis (HLH) diagnosed and treated in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed from January 2011 to December 2020. None of the patients had any underlying disease, and all were immunocompetent. The main clinical presentations were fever in all five patients, splenomegaly in four, enlarged lymph nodes in two, liver enlargement in one, and rash in three. Pulmonary infection was found in three patients, two of whom developed respiratory failure. Two patients had jaundice. Central nervous system symptoms and gastrointestinal bleeding were observed in one case. All patients received glucocorticoids and antiviral therapy. One patient was treated with the COP (cyclophosphamide+vincristine+prednisone) chemotherapy regimen after antiviral therapy failed and he developed central nervous system symptoms. After treatment, four patients achieved remission, but the fifth pregnant patient eventually died of disease progression after delivery. CMV-associated HLH in an immunocompetent individual without underlying diseases is extremely rare, and most patients have favorable prognosis. Antiviral therapy is the cornerstone of CMV-HLH treatment.

Minimal Residual Disease Status Predicts Outcome in Patients With Previously Untreated Follicular Lymphoma: A Prospective Analysis of the Phase III GALLIUM Study.

We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968) trial. Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders. MRD status was assessed at predefined time points (mid-induction [MI], end of induction [EOI], and at 4-6 monthly intervals during maintenance and follow-up). Patients with evaluable biomarker data at diagnosis were included in the survival analysis. MRD positivity was associated with inferior progression-free survival (PFS) at MI (hazard ratio [HR], 3.03 [95% CI, 2.07 to 4.45]; P < .0001) and EOI (HR, 2.25 [95% CI, 1.53 to 3.32]; P < .0001). MRD response was higher after G- versus R-chemotherapy at MI (94.2% v 88.9%; P = .013) and at EOI (93.1% v 86.7%; P = .0077). Late responders (MI-positive/EOI-negative) had a significantly poorer PFS than early responders (MI-negative/EOI-negative; HR, 3.11 [95% CI, 1.75 to 5.52]; P = .00011). The smallest proportion of MRD positivity was observed in patients receiving bendamustine at MI (4.8% v 16.0% in those receiving CHOP; P < .0001). G appeared to compensate for less effective chemotherapy regimens, with similar MRD response rates observed across the G-chemo groups. During the maintenance period, more patients treated with R than with G were MRD-positive (R-CHOP, 20.7% v G-CHOP, 7.0%; R-CVP, 21.7% v G-CVP, 9.4%). Throughout maintenance, MRD positivity was associated with clinical relapse. MRD status can determine outcome after induction and during maintenance, and MRD negativity is a prerequisite for long-term disease control in FL. The higher MRD responses after G- versus R-based treatment confirm more effective tumor cell clearance.

Indolent Lymphoma Care Delivery and Outcomes during the COVID-19 Pandemic in Ontario, Canada

Background At the outset of the coronavirus infectious disease 2019 (COVID-19) pandemic, hematological malignancy was recognized as a risk factor for severe COVID-19 disease, particularly patients with lymphoma, presenting a unique challenge for optimal management of indolent non-Hodgkin lymphoma (iNHL). To this end, professional societies including ASH favoured less immunosuppressive treatment regimens and omission of rituximab maintenance therapy. However, the implications of these recommendations on the care delivery and outcomes of patients with iNHL are unclear. Accordingly, we examined treatment selection, healthcare utilization, and COVID-19 outcomes of patients with iNHL receiving front line systemic treatment during pre-pandemic vs. pandemic period. Methods We performed a retrospective cohort study using administrative databases in Ontario, Canada, comparing outcomes in patients with iNHL who initiated first-line (1L) treatment with rituximab (R) monotherapy, or with bendamustine (B) or cyclophosphamide, vincristine, prednisone (CVP) from Jan 1, 2015 - Dec 31, 2018 (pre-pandemic cohort) and from Sept 1, 2019 - Aug 1, 2020 (pandemic cohort), with end of follow-up Mar, 31 2022. The primary outcome was comparison of treatment pattern before and during the COVID-19 pandemic which includes the following: 1L regimen received (R-CVP vs. B-R vs. R monotherapy), number of cycles received, dose delays, use of rituximab maintenance, and time-to-completion of full rituximab maintenance course (funded in Ontario every 3 months for 8 doses). Secondary outcomes were death, toxicities, healthcare utilization (emergency department [ED] visit, hospitalization, and ICU admission), and COVID-19 outcomes (SARS-CoV-2 PCR-confirmed infection, ED visit, hospitalization, and death). Adjusted odds ratios (aOR) and hazard ratios (aHR) with 95% confidence intervals (CI) from logistic regression and cause-specific proportional hazards models, respectively, were used to estimate associations between covariates (age, sex, comorbidity burden as measured by Aggregated Disease groups) and outcomes. Results We identified 4,143 patients (1,079 pandemic, 3,064 pre-pandemic), median age 69 (interquartile range 60-76) years, 44% female. In both pre- and pandemic periods, B-R was the most frequent prescribed regimen, with no difference in number of cycles given or in treatment delays (Table). During the pandemic, fewer patients received rituximab maintenance (69.6% vs 75.9%; aOR 0.72, 95% CI 0.60-0.88, p=0.0012). Older age was associated with lower odds of rituximab maintenance initiation (age 75+ vs. age &amp;lt; 60 aOR 0.44, 95% CI 0.35-0.56, p&amp;lt;0.0001). Moreover, patients who initiated maintenance during the pandemic period were less likely to complete the full maintenance course (48.7% vs 56.3%) (aHR 0.81, 95% confidence interval [CI] 0.71-0.92, p=0.0010) (Table) (Figure). Patients treated during the pandemic had less healthcare utilization (ED visit aHR 0.77, 95% CI 0.68, 0.88, p&amp;lt;0.0001; hospitalization aHR 0.81, 95% CI 0.70-0.94, p=0.0067) and treatment-related complications (infection aHR 0.69, 95% CI 0.57-0.82, p&amp;lt;0.0001; febrile neutropenia aHR 0.66, 95% CI 0.47-0.94, p=0.020), with no difference in death (aHR 0.79, 95% CI 0.58-1.08, p=0.14, Table). For COVID-19 outcomes, there were 131 SARS-CoV-2 infections from the beginning of the pandemic until December 31, 2021; with follow-up until March 31, 2022, there were 30 ED visits, 56 hospital admissions, and 23 ICU admissions, and 45 deaths related to COVID-19. Rituximab use (first dose to 1-year post-last dose) was associated with higher risk of COVID-19 infection (aHR 1.56, 95% CI 1.09-2.24, p=0.015) and COVID-19 complications (ED visit aHR 4.28, 95% CI 1.79-10.26, p=0.001; hospitalization/death 1.81, 95% CI 1.11-2.93, p=0.016). Primary vaccination series was associated with lower risk of infection and severe outcomes (infection aHR 0.52, 95% CI 0.28-0.97, p=0.04; hospitalization/death aHR 0.36, 95% CI 0.14-0.94, p=0.036; death aHR 0.26, 95% CI 0.07-0.89, p=0.033). Conclusion During the pandemic, B-R remained the preferred regimen for iNHL treatment, while rituximab maintenance use was less. Despite similar 1L regimen use, healthcare utilization and infectious complications were less in the pandemic cohort. Rituximab use was associated with nearly 2-fold risk of COVID-19 hospitalization/death.

Outcomes of patients with indolent lymphoma treated with bendamustine plus rituximab compared to rituximab plus CVP or CHOP chemoimmunotherapy in Ontario.

Bendamustine (B) with rituximab (R) has become the preferred regimen for patients with indolent lymphoma in Ontario, Canada, compared to R with cyclophosphamide, vincristine, prednisone (CVP) or cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). We conducted a propensity-matched retrospective cohort population-based study of patients treated with R-CVP/CHOP from 2005 to 2012 and patients treated with BR from 2013 to 2018. The primary outcome was 5-year overall survival (OS), and secondary outcomes included toxicities and healthcare utilization. The 5-year OS for patients treated with BR (n = 2023) and R-CVP/CHOP (n = 2023) was 80% and 75% respectively. Treatment with BR was associated with improved OS (HR 0.79, 95% CI 0.69-0.91). During the first 9 months, patients treated with BR versus R-CVP/CHOP had a higher number of admissions for infection (22% compared to 17%, p < 0.01) and a higher number of mean ED visits (mean 1.01 ± 1.68 visits vs. 0.85 ± 1.51 visits, p < 0.01). This trend persisted for 3 years. The adjusted 5-year OS for patients 75 years and older did not differ based on treatment regimen (55.5% for BR vs. 55.4% for R-CVP/CHOP). Our study supports the use of BR for patients with indolent lymphoma requiring treatment but suggests increased risk of certain toxicities warranting careful patient selection.

PB2141: CLINICOPATHOLOGICAL FEATURES AND OUTCOME OF CD5 POSITIVE DIFFUSE LARGE B CELL LYMPHOMA AND THE SIGNIFICANCE OF CD5 EXPRESSION STRENGTH: 10-YEAR SINGLE CENTER EXPERIENCE

Background: CD5 positive (CD5+) diffuse large B cell lymphoma (DLBCL) is a rare subtype of DLBCL encompassing 5-10% of patients (pts) with DLBCL, and it is characterized by poor outcome. Aims: To identify clinicopathological features of CD5+ DLBCL in a cohort of pts managed at Clinic for Hematology, Clinical Center of Serbia during a 10-year period (2012-2021). Methods: We retrospectively analyzed immunohistochemistry (IHC) results of biopted tumor tissue of 537 pts with DLBCL NOS. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results: Out of a total of 537 pts, in 211 (39.3%) CD5 was not analyzed by IHC, while in the remaining 326 (60.7%) was. Among them, 27 (8.3%) were found to be positive for CD5, out of which 10 pts were designated at the pathology report as CD5 +/- (5 pts) or CD5 -/+ (5 pts), while the rest 17 pts were clearly CD5+. In CD5 positive cohort, 52% of pts were men and median age at diagnosis was 63 years. ECOG performance status (PS) was poor (≥2) in 8 (29.6%) pts. One third of pts had advanced stage disease (Ann Arbor III/IV), while the rest two thirds were limited stage (I and II). Eleven out of 26 pts (42.3%) presented with B symptoms, 3/26 (11.5%) expressed bulky disease, while two thirds presented with extranodal disease. More pts (13/23 or 56.5%) were of nonGCB subtype according to IHC, while 4 out of 11 pts (36.4%) analyzed for c-myc protein expression were double expressors. Median Ki-67 proliferative index was 80%. Almost half of pts (47.6%) had increased initial lactate dehydrogenase (LDH) activity, while median beta-2 microglobulin (b2m) level was 3.38 mg/L. Nine out of 26 pts (34.6%) were IPI>2, while the rest 17 pts were IPI 0-1. Vast majority (25/27, 92.6%) were treated with chemoimmunotherapy in the first line, most of them with anthracycline-based protocols, 1 patient received cyclophosphamide, vincristine, prednisone (COP), and 1 patient succumbed before treatment commencement. Among treated pts with known outcome after first line, 18 (72%) pts achieved complete remission, 4 (16%) achieved partial response, while 3 (12%) pts did not respond to treatment. Median progression-free survival (PFS) after first treatment line for all pts in CD5 positive cohort was 25 months (95%CI 13.76-36.24), while median overall survival (OS) was not reached. Age at diagnosis, presence of B symptoms, and extranodal disease did not significantly influenced PFS and OS. Patients with bulky disease, nonGCB subtype, and double expressors experienced significantly shorter PFS (p=0.03, P=0.043, and p=0.025, respectively), but these features did not impact OS. On the other hand, b2m levels >3.38 mg/L, LDH >1x upper limit normal, and IPI >2 were significantly associated with shorter OS (p=0.014, p=0.01, and p=0.015, respectively), while they were not significant regarding PFS. ECOG PS >1 was significantly associated with both poor PFS and OS (p=0.005 and p=0.002, respectively). Intrestingly, pts designated as CD5+ at pathology reports experienced median PFS of 20 months in contrast to 52 months in pts descripted as CD5+/- and CD5-/+ (p=0.021). However, the difference between these two subgroups regarding OS was not observed. Summary/Conclusion: In our CD5+ DLBCL cohort, bulky disease, nonGCB, and double expressors were associated with shorter PFS, higher b2m, LDH, and IPI correlated with shorter OS, while higher ECOG PS was associated with shorter both PFS and OS. Median PFS after 1st treatment line was around 2 years, while median OS was not reached. Strenght of CD5 expression was significantly associated with PFS. CD5 should be mandatory within IHC for DLBCL.

Outcomes of Patients with Indolent Lymphoma Treated with Bendamustine Plus Rituximab Compared to Rituximab Plus CVP or CHOP Chemoimmunotherapy in Ontario

BackgroundFor patients with symptomatic advanced stage indolent lymphoma, rituximab (R) was traditionally used alongside cyclophosphamide, vincristine, prednisone (CVP), or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Bendamustine plus rituximab (BR) has been found to increase progression-free survival compared to R-CVP/CHOP, albeit with possible increased toxicity. Since 2013, bendamustine has been approved for public reimbursement for treatment of indolent lymphomas in Ontario, Canada, and has become the preferred regimen. We aimed to assess survival and toxicity of patients with indolent lymphoma treated with BR compared with R-CVP/CHOP in Ontario.MethodsWe conducted a retrospective cohort population-based study using administrative healthcare databases from Ontario, Canada. Patients were included if they had a diagnosis of indolent lymphoma and were treated with R-CVP/CHOP from 2005-2012, or with BR from 2013-2018. Patients with mantle cell lymphoma were excluded. Treatment groups were propensity score matched based on lymphoma subtype, age, sex, prior cancer diagnosis, time since diagnosis and rural or urban residence. The primary outcome of the study was overall survival (OS) from time of first treatment to death or end of study period. Secondary outcomes included toxicities during the first nine months of treatment, such as infections and secondary malignancies, associated resource utilization, and outcomes of patients treated with rituximab maintenance therapy. Cox regression models were used to assess factors associated with mortality.ResultsA propensity-matched cohort of 2032 patients treated with BR and 2032 treated with R-CVP/CHOP (1473 patients treated with R-CVP, 559 patients treated with R-CHOP) were included. The median age of patients was 65 years and 48% were female. A majority of patients had a diagnosis of follicular lymphoma (58.9% of patients treated with BR, 59.7% of patients treated with R-CVP/CHOP, p=0.59). Median follow-up time was 41 and 87 months for patients treated with BR and R-CVP/CHOP, respectively.BR was associated with significantly lower mortality compared to R-CVP/CHOP (HR 0.77, 95% CI 0.67-0.89, p<0.01). Five-year OS was 80% and 75% for patients treated with BR and R-CVP/CHOP, respectively (Figure 1). A total of 969 patients died during a follow-up period of seven years - 331 (16.3%) treated with BR and 638 (31.4%) treated with R-CVP/CHOP. Causes of death were available in 861 patients (88.9%), shown in Table 1. Most patients in both groups died from lymphoma (66.9% treated with BR, 66.4% treated with R-CVP/CHOP, p=0.88). A Charlson comorbidity index greater than or equal to 2 was associated with increased mortality (HR 3.04, 95% CI 2.45-3.77).Treatment toxicities are listed in Table 2. Over a nine-month period after treatment initiation (induction), patients treated with BR had a mean of 0.85 emergency department visits compared to a mean of 1.01 for patients treated with R-CVP/CHOP (p<0.01). Admissions for febrile neutropenia were more common in patients treated with R-CVP/CHOP compared to BR (4.9% vs. 2.2%, p<0.01), whereas infections resulting in hospitalization were more common in patients treated with BR. (21.9% vs. 17.3%, p<0.01).A majority of patients in both cohorts received maintenance therapy (81% of patients treated with BR, 64.1% of patients treated with R-CVP/CHOP). The use of maintenance therapy with either regimen was associated with less mortality (HR 0.16, 95% CI 0.14-0.19). Among patients who received maintenance therapy, patients previously treated with BR had more hospital admissions for fever (21.5% vs. 18.3%, p=0.03) and infections (37.9% vs. 31.5%, p<0.01) over a three-year period.ConclusionIn these well-matched cohorts of patients with indolent lymphoma, improved OS was seen with BR compared to R-CVP/CHOP. Patients treated with BR had more infectious complications, although more episodes of febrile neutropenia were seen in patients treated with R-CVP/CHOP. The use of maintenance therapy was associated with less mortality, although patients who received maintenance therapy may have been a more fit and selected population. Higher infectious toxicities were seen for patients who received maintenance rituximab after BR. This study supports BR as the standard of care, and future prospective studies should evaluate the survival and toxicity impact of rituximab maintenance. [Display omitted] DisclosuresPrica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria.

TCL-361: Bendamustine as Front-Line Therapy in T-Cell Prolymphocytic Leukemia: A Monocentric Experience

Introduction T-cell prolymphocytic leukemia (T-PLL) is a rare T-cell-neoplasm that is characterized by uncontrolled proliferation of mature T-cell lymphocytes with a very poor prognosis. Nowadays, alemtuzumab as a single agent is the best available option for both treatment-naive and relapsed/refractory patients; however, its efficacy is hampered by various adverse events (AEs) such as infusion-associated reactions, autoimmune AEs, and opportunistic infections. Objective We conducted a monocentric, retrospective study to evaluate the safety and efficacy of bendamustine, which is a bifunctional mechlorethamine derivative with alkylating and antimetabolite activities, as first-line therapy in patients unfit for alemtuzumab. Patients and Methods We collected clinical and biological data of 7 T-PLL patients treated with bendamustine between 2014 and 2020 in our institution. Four out of seven (57%) were males, the median age at diagnosis was 73 years (65–83 years). The median time from diagnosis to treatment was 15 months. Bendamustine was administered intravenously (90 mg/m2 on days one and two, every four weeks) for up to six cycles. Results Overall response rate was 57%, 3 patients achieved complete response (43%), and one partial response (14%). One patient experienced stable disease, and two patients progressed during treatment. Five patients (71%) experienced a relapse. Median overall survival (OS) was 63.7 months (19–108); median OS for responding patients was 187 months versus 24 months for non-responding patients (p=0.093). Median progression-free survival (PFS) was 12 months (11–13). Three patients received second-line therapy: one patient was treated with gemcitabine; the others received a second bendamustine course. Two patients received a third-line therapy with combination chemotherapy: COMP (prednisone, cyclophosphamide, vincristine, myocettm) and CVP (cyclophosphamide, vincristine, prednisone). Two patients experienced infusion-associated reactions. Four patients experienced hematological toxicities: one thrombocytopenia G3, 3 neutropenia G3 requiring G-CSF administration. Four patients received co-trimoxazole prophylaxis, one received acyclovir prophylaxis. One patient experienced herpetic retinitis. Premature termination ( Conclusions Our data are consistent with scientific literature. This treatment is feasible and safe, with an acceptable toxicity profile. Although alemtuzumab remains the standard of care of this rare disease, bendamustine might be a valid option either for unfit patients or for undeferrable disease.

SWOG 1312 Final Results: A Phase 1 Trial of Inotuzumab in Combination with CVP (Cyclophosphamide, Vincristine, Prednisone) for Relapsed/ Refractory CD22+ Acute Leukemia

SWOG 1312 Final Results: A Phase 1 Trial of Inotuzumab in Combination with CVP (Cyclophosphamide, Vincristine, Prednisone) for Relapsed/ Refractory CD22+ Acute Leukemia

Prophylactic Antiemetics for Haematological Malignancies: Prospective Nationwide Survey Subset Analysis in Japan.

Although neurokinin-1 receptor antagonists are approved chemotherapy drugs in Japan, no nationwide surveys have been performed to validate chemotherapy-induced nausea and vomiting (CINV) guidelines in clinical practice. This study evaluated CINV in patients with haematological malignancies starting first-time chemotherapy. A nationwide CINV survey on patients with haematological malignancies was conducted at 118 institutions. Patients undergoing moderately emetic chemotherapy (n=17) and highly emetic chemotherapy (HEC; n=180) were compared. Forty-one patients undergoing HEC received triple antiemetics. Female gender and young age were risk factors for early-phase nausea, while female gender remained a risk factor for late-phase nausea and vomiting. Among 125 patients receiving CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)-like regimens, complete response and complete control were increased in patients receiving triple antiemetics, compared to those with double antiemetics. Guideline compliance was very low. Although not statistically significant, there was a trend for reduced CINV and improved disease control for triple versus double antiemetics, suggesting that triple antiemetics should be considered for HEC, especially in young female patients with non-Hodgkin lymphoma receiving CHOP-like regimens.

Clinical features and treatment outcomes of blastic plasmacytoid dendritic cell neoplasm: a single-center experience in Korea

Background/AimsBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that typically presents in the form of skin manifestations with or without lymph node and bone marrow involvement. Given its rarity and recent recognition as a distinct pathological entity, no standard of treatment exists for this aggressive disease and its prognosis is particularly dismal.MethodsWe retrospectively analyzed clinical features and treatment outcomes of patients who were diagnosed with BPDCN between 2000 and 2014.ResultsTen patients had a median age at diagnosis of 41 years (range, 18 to 79), and seven patients were male. Sites of disease involvement were the skin (n = 7), lymph node (n = 5), bone marrow (n = 2), liver (n = 2), spleen (n = 2), and soft tissue (n = 1). Intensified chemotherapy regimens such as hyperCVAD regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine), and VPDL (vincristine, methylprednisolone, daunorubicin, L-asparaginase) were used as a first-line treatment. Although all patients treated with intensified chemotherapy showed an objective response (five patients with complete response) with median progression-free survival of 11.2 months (range 6.2 to 19.4), complete remission was not sustained for more than 2 years in any case. The response was relatively long-lived compared with previously reported CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)-like regimens, but the above regimens do not result in long-term remission.ConclusionsAll patients treated with hyperCVAD or VPDL showed an objective response, but the duration of response was relatively short. Thus, the development of more effective induction as well as consolidation treatment strategy should be warranted to improve this rare disease entity.

ASCO 2017 Meeting Summary: Updates to Practice-Changing Studies in Untreated Non-Hodgkin Lymphoma

The 2017 annual meeting of the American Society of Clinical Oncology took place in Chicago, Illinois, 2–6 June. At the meeting, results from key studies in the first-line treatment of indolent non-Hodgkin lymphoma (iNHL) were presented. Of those studies, two were selected for oral presentations: 9-year follow-up data from the STiL NHL1 trial, which compared the efficacy and safety of bendamustine plus rituximab (BR) with those of rituximab plus cyclophosphamide–vincristine–prednisone–doxorubicin (R-CHOP); and 5-year follow-up data from the bright study, which compared BR with R-CHOP and R-CVP (rituximab plus cyclophosphamide–vincristine–prednisone) combined. Our meeting report describes the foregoing studies and includes interviews with key investigators, plus commentaries from three Quebec hematologists on the potential effects for Canadian practice.

CLINICAL FEATURES AND SURVIVAL OUTCOMES ON LYMPHOPLASMACYTIC LYMPHOMA PATIENTS WITH NON‐IGM PARAPROTEINEMIA COMPARED WITH IGM PARAPROTEINEMIA IN KOREA

Introduction: The incidence of lymphoplasmacytic lymphoma (LPL), a relatively rare subset of non-Hodgkin lymphoma, has been suggested lower in Asian population than in Western countries. Non-IgM LPL is rare and accounts for less than 5% of the total LPL cases. There have been few studies comparing the clinical features and survival outcomes between patients with non-IgM LPL and LPL/Waldenström macroglobulinemia (WM) in East Asia. In this study, we evaluated clinical features and survival outcomes of LPL with non-IgM compared with LPL/WM in Korea. Method: A retrospective analysis was performed for patients diagnosed with non-IgM LPL and LPL/WM at Asan Medical Center between January 2001 and March 2016. Clinical features and survival outcomes were compared between the two groups. Result: A total of 19 patients were categorized into non-IgM (n = 8, 42.1%) and LPL/WM (n = 11, 57.8%) groups. The median age at diagnosis was 65.5 (62 to 69) and 57 (range 47 to 66) years, respectively; 7 (87.5%) patients in non-IgM LPL and all patients in LPL/WM were men. There were no statistically significant differences in baseline characteristics between non-IgM LPL and LPL/WM groups, except the proportion of high/high-intermediate subset according to International prognostic index (IPI) (75% vs 18.2%, p = 0.024). The patients in LPL with non-IgM group more frequently showed extranodal involvement of ≥2 (62.5% vs. 27.3%) and demonstrated higher level of beta-2-microglobuin level than those in LPL/WM group [median, 12.8, (range, 2.3–41.0) vs. 3.7, (2.2–30.0)] without statistical significance. Patients were treated with heterogeneous regimens including CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), CVP (cyclophosphamide, vincristine, prednisone), and fludarabine. The median overall survival of the LPL with non-IgM group was shorter than that of LPL/WM (10 months [95% CI, 0–36.3] vs median 81 months [95% CI, 0–168]; p = 0.124). Conclusion: Despite a small number of patients and heterogeneous treatment, more unfavorable prognostic factors with regard to IPI in non-IgM LPL group might be consistent with worse survival outcomes compared to LPL/WM group. These findings suggest IPI might be useful for predicting prognosis in non-IgM LPL and LPL/WM. Further studies are needed to clarify the clinical features and survival outcomes between two groups. Keywords: lymphoplasmacytic lymphoma (LPL); lymphoplasmacytic lymphoma/Waldenstroem (LPL/WM).

Preference for subcutaneous or intravenous administration of rituximab among patients with untreated CD20+ diffuse large B-cell lymphoma or follicular lymphoma: results from a prospective, randomized, open-label, crossover study (PrefMab)

The aim of this study was to evaluate patient preference and satisfaction for the subcutaneous (s.c.) versus intravenous (i.v.) formulation of rituximab given with chemotherapy in previously untreated patients with CD20+ diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients received eight cycles of rituximab according to 2 schedules: Arm A received 1 cycle rituximab i.v. (375 mg/m2) and 3 cycles rituximab s.c. (1400 mg) then 4 cycles rituximab i.v.; Arm B received 4 cycles rituximab i.v. (375 mg/m2) then 4 cycles rituximab s.c. (1400 mg). Alongside rituximab, both arms received 6-8 cycles of chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), cyclophosphamide, vincristine, prednisone (CVP), or bendamustine as per standard local practice). Preference for s.c. or i.v. administration was evaluated using the Patient Preference Questionnaire (PPQ) at cycles 6 and 8. Patient satisfaction and convenience were assessed using the Cancer Therapy Satisfaction Questionnaire (CTSQ), and Rituximab Administration Satisfaction Questionnaire (RASQ) at cycles 4 and 8. At the primary data cut-off (19 January 2015), the intent-to-treat population comprised 743 patients. The majority had DLBCL (63%) and baseline characteristics were balanced between arms. At cycle 8, 81% of patients completing the PPQ preferred rituximab s.c. Preference was not impacted by treatment sequence or disease type. Patient satisfaction as measured by RASQ was higher for s.c. versus i.v. CTSQ scores were similar between arms. Adverse events were generally balanced between administration routes and no new safety signals were detected. Most previously untreated patients with CD20+ DLBCL or FL preferred s.c. to i.v. rituximab administration. Patient satisfaction with rituximab treatment was generally greater with s.c. administration. NCT01724021 (ClinicalTrials.gov).

A Phase 1 Trial of Inotuzumab in Combination with CVP (Cyclophosphamide, Vincristine, Prednisone) for Relapsed/ Refractory CD22+ Acute Leukemia (SWOG 1312)

The prognosis of patients (pts) with relapsed/ refractory acute lymphoblastic leukemia (ALL) remains poor and novel therapies are needed. The anti-CD22 immunoconjugate inotuzumab ozogamicin (INO) has demonstrated promising results in both phase 2 and 3 trials (Kantarjian et al. Lancet Oncology 2012; 13(4): 403-11). Pre-clinical studies have demonstrated superior anti-tumor activity when INO is co-administered with cyclophosphamide (C), vincristine (V), and prednisone (P). In this study, SWOG 1312, we assess the safety of INO in combination with CVP and determine the maximum tolerated dose (MTD) of INO in this regimen for patients with relapsed or refractory (R/R) CD22+ acute leukemia (B-ALL, mixed phenotype, and Burkitts). Here, we present our toxicity results.Methods: Pts were treated at limited SWOG institutions from Apr 2014 to present. INO was supplied by Pfizer and an IND was approved by the FDA. The protocol was reviewed and approved by each institutional review board. Eligibility criteria included: age > 18 years (yrs), > 20% blasts expressing CD22, R/R CD22+ acute leukemia (B-ALL, mixed phenotype, or Burkitts), and adequate organ function. All pts received treatment with C (750 mg/m2) intravenous (IV) Day 1, V (1.4 mg/m2) (max 2 mg) IV Day 1, P (100 mg) orally Days 1-5 and IO (dose escalated as in Table 1) IV Days 1, 8, and 15. Each cycle was 28 days, and a maximum of 6 cycles could be administered. Dose escalation was performed using a standard 3x3 design; with the plan to treat 12 pts once the MTD was defined. Dose limiting toxicities (DLTs) were considered: (1) > Grade 4 non-hematologic toxicities with the exception of nausea, vomiting and toxicities secondary to neutropenia and sepsis; (2) prolonged myelosuppression [absolute neutrophil count (ANC) < 500/ uL or platelet count < 25,000/uL] in a bone marrow with < 5% blasts and no evidence of leukemia that lasts > 35 days beyond the most recent dose of IO; (3) any grade 3 non-hematologic toxicity (excluding peripheral neuropathy, hyperglycemia, and toxicities secondary to neutropenia, thrombocytopenia, and sepsis) that does not resolve to Grade 2 or better by 7 days beyond the most recent dose of IO; (4) any > Grade 3 elevation in SGOT/ SGPT or bilirubin lasting ≥ 7 days; (5) any IO-related toxicity resulting in permanent discontinuation of IO.Results: As of 7/14/2016, 24 pts have been enrolled: 2 pts were ineligible and 3 pts are currently receiving treatment and are not evaluable for toxicity. Of the 19 evaluable pts, the median age was 49 yrs (range 21-75), 10 (53%) were male, and the median WBC at registration was 9.4 K/uL (range 0.9-59.6). All pts had B-ALL. The median time from initial diagnosis to registration was 774 days. Five pts were in 1st relapse, 8 in 2nd relapse, 3 in 3rd relapse, 1 in 4th relapse, and 2 pts were primary refractory. Five pts had received prior allogeneic hematopoietic stem cell transplant (AHSCT); 7 pts had poor risk cytogenetics (Ph+, -7, +8, complex, or hypodiploid). One death occurred during treatment and was attributed to pneumonia. Grade 3-4 hematologic toxicity related to treatment was common: neutropenia (11 pts), thrombocytopenia (7 pts), and anemia (6 pts). Grade 3-4 non-hematologic toxicities were almost exclusively febrile neutropenia. One DLT occurred at Dose Level 3: prolonged myelosuppression. No cases of hepatic veno-occlusive disease (VOD) occurred during treatment, and 1 pt experienced Grade 3 alkaline phosphatase at Dose Level 1. Three pts proceeded to AHSCT after study treatment; 1 pt developed VOD post AHSCT however, this fully resolved. Currently, 3 pts have been enrolled to Dose Level 4.Conclusion: The combination of CVP/IO is well tolerated and only 1 significant hepatic event (which subsequently resolved) was observed despite a heavily pre-treated group of patients. Further toxicity results and dose escalation will be presented at the meeting. Response data will also be presented if enrollment is complete. [Display omitted] DisclosuresAdvani:Pfizer: Consultancy, Research Funding. Othus:Glycomimetics: Consultancy; Celgene: Consultancy. Erba:Pfizer: Consultancy; Juno: Research Funding; Gylcomimetics: Other: DSMB; Agios: Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Astellas: Research Funding; Agios: Research Funding; Juno: Research Funding; Daiichi Sankyo: Consultancy; Celator: Research Funding; Gylcomimetics: Other: DSMB; Pfizer: Consultancy; Millennium Pharmaceuticals, Inc.: Research Funding; Sunesis: Consultancy; Seattle Genetics: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Jannsen: Consultancy, Research Funding; Ariad: Consultancy; Novartis: Consultancy, Speakers Bureau; Celator: Research Funding; Incyte: Consultancy, DSMB, Speakers Bureau; Pfizer: Consultancy; Celgene: Consultancy, Speakers Bureau; Jannsen: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Sunesis: Consultancy; Gylcomimetics: Other: DSMB; Pfizer: Consultancy; Sunesis: Consultancy; Ariad: Consultancy; Celator: Research Funding; Jannsen: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Ariad: Consultancy; Astellas: Research Funding; Astellas: Research Funding; Celator: Research Funding; Agios: Research Funding; Agios: Research Funding; Juno: Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Juno: Research Funding; Gylcomimetics: Other: DSMB; Astellas: Research Funding; Jannsen: Consultancy, Research Funding; Ariad: Consultancy.

Results from Hemato-Oncology Latin America Observational Registry (HOLA) Providing Real World Outcomes for the Treatment of Patients with CLL

Introduction: There are few reports of standard of care and outcomes in Latin America. The HOLA study is a retrospective chart review of patients with B-cell malignancies in Latin America (LATAM).Methods: The objective of this registry is to describe patient characteristics, diagnostic and treatment patterns, and clinical outcomes in patients with Chronic Lymphocytic Leukemia (CLL) from a mix of public and private sites in Brazil, Mexico, Chile, Argentina, Colombia, Guatemala, and Panama. We report 472 patients with CLL diagnosed in the period from January 2006 to March 2016.Results: Median age at diagnosis was 66 years (range 23 - 95). Male gender predominance (53.6 vs 46.4%). Twenty-three percent of the patients (n=103) were dead, median time from diagnosis to death of 2.4 years (range 0-6.6 years). Seventeen percent (n=19) died before frontline treatment, 35%(39) after first-line treatment, 19%(21) in second-line, 27%(30) at or after third-line treatment.Anemia reported on 34%. Of the 34% (n=162) patients with COOMBS test, it was positive on 13%.Frequent comorbidities were high blood pressure (46%), heart disease (17%) and diabetes (15%).Binet status reported on 63% of patients, Rai status on 55%. (Table 1)Flow cytometry missing on 27% of patients (not performed/missing report). Diagnostic markers were positive as follows: CD23, 94% and CD5, 92%. Prognostic markers: 52% tested for CD38 and 10% ZAP 70, positivity on 24% and 26% of tested patients, respectively. Cytogenetic/FISH test performed on 21% (102), del(17p) was present on 7.4% of tested patients at diagnosis.Seventy two per cent of patients were considered for watch- and-wait approach. Median time from diagnosis to treatment initiation was 113 days (range 1 -2808).Sixty one per cent (288/472) receive front line treatment at any time. Frequent reasons to start treatment were B symptoms (25%), anemia (21%) and lymphocyte doubling time <6 months (17%). (Table 2)Response was assessed by clinical exam and blood count in 95% of patients, CT scan 24 %, abdominal ultrasonography 12%.Twenty-eight per cent of patients (135) relapsed and received second-line treatment. The most frequent second-line treatments were Chlorambucil (Chl) 37%; Fludarabine + Cyclophosphamide (FC) 16%, Cyclophosphamide + Vincristine + Prednisone (CVP) 9%. Clinical complete responses were as follows: FC = 4.5%, FCR= 25%.Sixty-five out of 472 patients (14%) received third-line treatment. Most frequently used treatments at this line were: Chlorambucil 23%, FC 20%, CVP 13%, FCR 9.2%, BR 4.6 %, and other chemotherapies 4.6%.Only 7% of patients in the registry relapsed and received fourth-line treatment.Conclusions:HOLA registry describes patterns of demographics, diagnosis and treatments in the real world in Latin America. CLL diagnosis in Latin America is made based on flow cytometry for the majority of the patients. Cytogenetic and FISH test are scarcely performed.For the deceased patients, median time from diagnosis to death was 2.4 years. This could be related to the high risk, but since prognostic tests were not always present this merits further investigation.Watch-and-wait was the most frequent approach. Time elapsed from diagnosis to treatment initiation was less than a year. Lymphocyte doubling time as reason to start treatment was frequent.Chlorambucil remains the most frequently used treatment for elderly in newly diagnosed and relapsed /refractory patients, use is also frequent in the young/fit patient population. Access barriers to innovative drugs and monoclonal antibodies could explain this situation. [Display omitted] [Display omitted] DisclosuresChiattone:Janssen: Membership on an entity's Board of Directors or advisory committees; roche: Membership on an entity's Board of Directors or advisory committees; abbvie: Membership on an entity's Board of Directors or advisory committees. Gomez-Almaguer:Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Pavlovsky:Janssen: Speakers Bureau; Novartis: Speakers Bureau; Bristol Myers Squib: Speakers Bureau. Tuna-Aguilar:Janssen: Speakers Bureau. Farias:Janssen: Consultancy. Galvez:Novartis: Consultancy. Santos:Janssen: Employment. De La Mora Estrada:Janssen: Employment, Membership on an entity's Board of Directors or advisory committees.

Impact of Hodgkin or non-Hodgkin lymphoma and their treatments on sperm aneuploidy: a prospective study by the French CECOS network

To assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments. Multicenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24months. University hospitals. Forty-five HL and 13 NHL patients were investigated before and after treatment. Treatment regimens were classified in two groups: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without (±) radiotherapy, and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)/MOPP-ABV (mechlorethamine, oncovin, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine). A control group of 29 healthy men was also studied. Semen analyses and aneuploidy study by FISH were performed at each time point. Comparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment. Before treatment, HL and NHL men had altered semen characteristics and higher sperm aneuploidy rates (median 0.76 [interquartile range 0.56-0.64]) than the control group (0.54 [0.46-0.74]). After treatment, sperm production was significantly lowered 3 and 6months after ABVD ± radiotherapy or CHOP/MOPP-ABV. After ABVD ± radiotherapy, the aneuploidy rate increased significantly only at 3months, and values obtained 1 or 2years later were lower than pretreatment values. In contrast, in the CHOP/MOPP-ABV treatment group, semen characteristics and aneuploidy rate did not return to normal levels until 2years after treatment. Lymphoma itself has consequences on sperm aneuploidy frequency before treatment. Moreover, lymphoma treatments have deleterious effects on sperm chromosomes related to treatment type and time since treatment. Patient counseling is essential concerning the transient but significant sperm aneuploidy induced by lymphoma and its treatments.

Bendamustine for Patients with Indolent Lymphoma an Updated Meta-Analysis of Randomized Controlled Trials (RCT)

BackgroundIn 2011 we performed a systematic review and meta-analysis evaluating the efficacy of bendamustine for patients with indolent lymphoproliferative malignancies. We included 5 trials. Since then several new trials of bendamustine for indolent lymphoproliferative malignancies were conducted, and some are still ongoing. Individual trials supported a progression free survival (PFS) benefit but none was powered to demonstrate an effect on overall survival (OS).In order to evaluate the effect of bendamustine on the OS of patients with indolent lymphoproliferative malignancies we performed a systematic review and meta-nalysis of RCTs.MethodsWe included RCTs that compared bendamustine to other chemotherapy regimens for patients with indolent lymphoproliferative malignancies including chronic lymphocytic leukemia (CLL). We included patients in both first line and the relapsed setting. In July 2015 we searched The CochraneLibrary, MEDLINE, conference proceedings, and databases of ongoing trials. Two reviewers appraised the quality of trials and extracted data.The primary outcome wasall cause mortality. Secondary outcomes included: PFS, complete response (CR), and adverse events. Relative risk (RR) with 95% confidence intervals (CIs) were estimated and pooled for dichotomous data and hazard ratio (HR) for time to event data.ResultsWe identified 8 trials, conducted between the years 1994 and 2012 (one trial is ongoing) randomizing 2484 adult patients with a mean/median age of 58 - 74 years. The rate of patients with follicular lymphoma ranged between 40% to 70%, and mantle cell lymphoma 16% to 22% in the 3 trials that included patients with those types of lymphoma. Four trials included only patients with CLL. The comparisons were between bendamustine, vincristine, prednisone to cyclophosphamide, vincristine, prednisone (CVP); bendamustine-rituximab (BR) to cyclophosphamide, adriamycin, vincristine, prednisone, rituximab (RCHOP), RCVP; BR to fludarabine-rituximab and to fludarabine, cyclophosphamide, rituximab (FCR); and bendamustine to chlorambucil (+-rituximab).Bendamustine significantly reduced mortality risk of patients with indolent lymphoproliferative malignancies compared to control, RR for death 0.84; 95% CI 0.73 - 0.96, I2 = 0 (Figure). Including only CLL patients the RR is 0.84; 95% CI 0.69 - 1.03.PFS was improved with bendamustine in each of the trials and when trials were pooled, HR 0.55, 95% CI 0.41 - 0.74, I2 of heterogeneity 78%. The rate of CR improved with bendamustine compared to control for patients with indolent lymphoma, RR 1.40; 95% CI 1.09 - 1.81, random effects model, I2 = 46%. We did not pool results of CR of patients with CLL due to a high statistical heterogeneity. The rates of grade 3/4 infection or any grade 3/4 adverse events were not different between the arms.DiscussionThis meta-analysis shows that bendamustine decreases the risk of mortality of patients with indolent lymphoma and CLL compared to other chemotherapy. In addition, PFS is improved. Further analysis of results with longer follow up is expected. DisclosuresShpilberg:Gilead: Consultancy; Millennium Takeda: Consultancy. Raanani:Novartis: Other: Advisory Board, Research Funding; Ariad: Other: Advisory Board; BMS: Other: Advisory Board; Pfizer: Other: Advisory Board.

Impact of lymphoma treatments on spermatogenesis and sperm deoxyribonucleic acid: a multicenter prospective study from the CECOS network

To determine consequences of lymphoma treatments on sperm characteristics and sperm DNA, and to evaluate predictors of sperm recovery. Multicenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months. University hospitals. Seventy-five Hodgkin lymphoma and non-Hodgkin lymphoma patients and a control group of 257 fertile men. Semen analyses, and sperm DNA and chromatin assessments. Comparisons of sperm characteristics before and after treatment. Patients already had altered sperm characteristics before lymphoma treatment, with no identified risk factor. Sperm count, total sperm count, motility, and vitality decreased after treatment, with lowest values at 3 and 6 months. Twelve months after treatment, mean sperm count recovered to pretreatment values after doxorubicin, bleomycin, vinblastine, darcarbacine (ABVD) or ABVD+radiotherapy, but not after doxorubicin, cyclophosphamide, vincristine, prednisone (CHOP) or mechlorethamine, oncovin, procarbazine, prednisone (MOPP) chemotherapies. It was noteworthy that 7% of patients remained azoospermic at 24 months. After 24 months, Kaplan-Meier estimates showed that more than 90% of patients will recover normal sperm count after ABVD or ABVD+radiotherapy vs. 61% for CHOP chemotherapies. In multivariate analyses including diagnosis and treatment protocol, only pretreatment total sperm count was related to recovery. Compared with a control group, lymphoma patients had higher sperm chromatin alterations and DNA fragmentation before any treatment. After treatment, DNA fragmentation assessed by TUNEL assay and sperm chromatin structure assay decreased from 3 and 6 months, respectively, while remaining higher than in the control group during follow-up. Lymphoma patients had altered sperm DNA and chromatin before treatment. Lymphoma treatment had damaging effects on spermatogenesis. These data on both the recovery period according to treatment modalities and the pre- and post-treatment chromatin status of sperm are useful tools for counseling patients wishing to conceive.

Feline mediastinal lymphoma: a retrospective study of signalment, retroviral status, response to chemotherapy and prognostic indicators

Historically, feline mediastinal lymphoma has been associated with young age, positive feline leukaemia virus (FeLV) status, Siamese breed and short survival times. Recent studies following widespread FeLV vaccination in the UK are lacking. The aim of this retrospective multi-institutional study was to re-evaluate the signalment, retroviral status, response to chemotherapy, survival and prognostic indicators in feline mediastinal lymphoma cases in the post-vaccination era. Records of cats with clinical signs associated with a mediastinal mass and cytologically/histologically confirmed lymphoma were reviewed from five UK referral centres (1998-2010). Treatment response, survival and prognostic indicators were assessed in treated cats with follow-up data. Fifty-five cases were reviewed. The median age was 3 years (range, 0.5-12 years); 12 cats (21.8%) were Siamese; and the male to female ratio was 3.2:1.0. Five cats were FeLV-positive and two were feline immunodeficiency-positive. Chemotherapy response and survival was evaluated in 38 cats. Overall response was 94.7%; complete (CR) and partial response (PR) rates did not differ significantly between protocols: COP (cyclophosphamide, vincristine, prednisone) (n = 26, CR 61.5%, PR 34.0%); Madison-Wisconsin (MW) (n = 12, CR 66.7%, PR 25.0%). Overall median survival was 373 days (range, 20-2015 days) (COP 484 days [range, 20-980 days]; MW 211 days [range, 24-2015 days] [P = 0.892]). Cats achieving CR survived longer (980 days vs 42 days for PR; P = 0.032). Age, breed, sex, location (mediastinal vs mediastinal plus other sites), retroviral status and glucocorticoid pretreatment did not affect response or survival. Feline mediastinal lymphoma cases frequently responded to chemotherapy with durable survival times, particularly in cats achieving CR. The prevalence of FeLV-antigenaemic cats was low; males and young Siamese cats appeared to be over-represented.

Fludarabine-based versus CHOP-like regimens with or without rituximab in patients with previously untreated indolent lymphoma: a retrospective analysis of safety and efficacy

Fludarabine-based regimens and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)-like regimens with or without rituximab are the most common treatment modalities for indolent lymphoma. However, there is no clear evidence to date about which chemotherapy regimen should be the proper initial treatment of indolent lymphoma. More recently, the use of fludarabine has raised concerns due to its high number of toxicities, especially hematological toxicity and infectious complications. The present study aimed to retrospectively evaluate both the efficacy and the potential toxicities of the two main regimens (fludarabine-based and CHOP-like regimens) in patients with previously untreated indolent lymphoma. Among a total of 107 patients assessed, 54 patients received fludarabine-based regimens (FLU arm) and 53 received CHOP or CHOPE (doxorubicin, cyclophosphamide, vincristine, prednisone, or plus etoposide) regimens (CHOP arm). The results demonstrated that fludarabine-based regimens could induce significantly improved progression-free survival (PFS) compared with CHOP-like regimens. However, the FLU arm showed overall survival, complete response, and overall response rates similar to those of the CHOP arm. Grade 3–4 neutropenia occurred in 42.6% of the FLU arm and 7.5% of the CHOP arm (P < 0.000). Moreover, the FLU arm also had a higher occurrence of infection than the CHOP arm (27.8% vs 8.5%; P = 0.034). Multi-factor regression of infection revealed that only age (>60 years) and presentation of grade 3–4 myelosuppression were the independent factors to infection, and the FLU arm had significantly higher myelosuppression. In conclusion, the present study revealed that the use of fludarabine-based regimens could induce high rates of myelosuppression over CHOP-like regimens, in spite of significant increases in PFS.