Tacrolimus/methotrexate vs tacrolimus/reduced-dose methotrexate/mycophenolate for graft-versus-host disease prevention.

Tacrolimus (Tac)/methotrexate (MTX) is standard graft-versus-host disease (GVHD) prophylaxis; however, is associated with several toxicities. Tac, reduced-dose MTX (mini-MTX), and mycophenolate mofetil (MMF) have been used but never compared with standard MTX. We performed a randomized trial comparing Tac/MTX (full-MTX) with Tac/mini-MTX/MMF (mini-MTX/MMF) for GVHD prevention after allogeneic hematopoietic cell transplantation (HCT). Patients (pts) receiving first myeloablative HCT using an 8/8 HLA-matched donor were eligible. Primary end points were incidence of acute GVHD (aGVHD), mucositis, and engraftment. Secondary end points included chronic GVHD (cGVHD), organ toxicity, infection, relapse, nonrelapse mortality (NRM), and overall survival (OS). Ninety-six pts were randomly assigned to full-MTX (N = 49) or mini-MTX (N = 47). The majority (86%) used bone marrow grafts. There was no significant difference in grade 2-4 aGVHD (28% mini-MTX/MMF vs 27% full-MTX; P = .41); however higher incidence of grade 3-4 aGVHD (13% vs 4%; P = .07) with mini-MTX/MMF. Pts receiving mini-MTX/MMF had lower grade 3 or 4 mucositis and faster engraftment. There were no differences in moderate-to-severe cGVHD at 1 year or infections. Pts receiving mini-MTX/MMF experienced less nephrotoxicity and respiratory failure. There was no difference in the 1-year relapse (19% vs 21%; P = .89) and OS (72% vs 71%; P = .08), and mini-MTX/MMF was associated with lower but nonsignificant NRM (11% vs 22%; P = .06). Compared with full-MTX, mini-MTX/MMF was associated with no difference in grade 2-4 aGVHD and a more favorable toxicity profile. The higher severe aGVHD warrants further study to optimize this regimen. The trial was registered at www.clinicaltrials.gov as #NCT01951885.

Toxicity analysis of busulfan pharmacokinetic therapeutic dose monitoring.

Busulfan-based conditioning regimens are associated with serious toxicities and literature reports increased risk of toxicities when daily area under the curve concentrations exceed 6000 µM-minute. We implemented real time pharmacokinetic-guided therapeutic drug monitoring of busulfan for myeloablative conditioning regimens. The objective was to compare toxicity of intravenous busulfan before and after therapeutic drug monitoring implementation. The primary endpoint was incidence of hepatotoxicity. Medical records were retrospectively reviewed with weight-based dose Busulfan/Cyclophosphamide (BuCy) conditioning from August 2017 through March 2018 (N = 14) and therapeutic drug monitoring from April 2018 through December 2018 (N = 22). Recipients of busulfan therapeutic drug monitoring were younger than those receiving weight-based dose (median: 45 vs. 58 years, p = 0.008). No other baseline differences were observed. There was no difference in hepatotoxicity between therapeutic drug monitoring and weight-based dose (median 1 vs. 0 days, p = 0.40). In the therapeutic drug monitoring group, 45% of patients had increases and 41% had decreases in busulfan dose after Bu1. Repeat pharmacokinetic after Bu2 were required in 32% of patients. A pharmacokinetic dose monitoring program for myeloablative conditioning intravenous busulfan regimens may be considered a safe practice in stem cell transplant recipients. The majority of patients receiving pharmacokinetic-guided therapeutic drug monitoring required dose changes and therapeutic drug monitoring patients had no significant difference in toxicity compared to those receiving weight-based dose.

The impact of socioeconomic disparities on the use of upfront autologous stem cell transplantation for mantle cell lymphoma.

Using the National Cancer Database, we identified 10,290 patients with newly diagnosed mantle cell lymphoma (MCL) treated with chemotherapy with or without upfront autologous stem cell transplantation (ASCT). Only 17% of patients underwent ASCT. Patients who underwent ASCT were younger and more likely to have lower comorbidity scores, private insurance, higher income and education, and treatment received at an academic facility. On multivariable analysis, age, comorbidity index, insurance type, the transition of care, facility type, distance to facility, and diagnosis year were predictive for ASCT use. ASCT use was associated with improved 5-year overall survival in younger (82% vs. 64%, p < .001) and older (70% vs. 40%, p < .001) patients, which was retained in the matched propensity score and 12-month analyses. Female gender, the diagnosis year ≥2009, private insurance, higher income, and education were associated with superior survival, whereas Black race and higher comorbidities predicted inferior survival.

Outcomes and factors impacting use of axicabtagene ciloleucel in patients with relapsed or refractory large B-cell lymphoma: results from an intention-to-treat analysis.

Data on real-world outcomes of axicabtagene ciloleucel (axi-cel) therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL) are limited. In this intent to treat (ITT) analysis, we reviewed records of 38 consecutive patients with R/R LBCL for whom axi-cel was intended. Twenty-seven (71%) patients received axi-cel and 11 (29%) did not. Patients in the non-axi-cel group had a higher hematopoietic cell transplantation comorbidity index (HCT-CI) (median 4 vs. 2, p = .04). Median overall survival for the ITT, axi-cel and non-axi-cel group was 10 (95% CI, 3.7 to 13), 13 (95% CI, 7.7 to N.R.) and 1 (95% CI, 0.4 to 3.7) month(s) respectively. Factors limiting axi-cel use were disease progression, sepsis, manufacturing failure and socioeconomic barrier in 6 (55%), 3 (27%), 1 (9%) and 1 (9%) patient(s) respectively. Additional strategies are needed to ensure all LBCL patients for whom chimeric antigen receptor (CAR) T-cell therapy is prescribed can receive this treatment.

Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma.

Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma (MM) is lacking in the current literature. We evaluated 258 patients with relapsed MM, diagnosed from 2008 to 2015, to investigate the prognostic impact of deep immunoparesis on post-relapse survival. On qualitative immunoparesis assessment, no, partial and full immunoparesis was present in 9%, 30% and 61% of patients, respectively. Quantitative immunoparesis was assessed by computing the average relative difference (ARD) between polyclonal immunoglobulin(s) and corresponding lower normal limit(s), with greater negative values indicating deeper immunoparesis. The median ARD was -39%, with an optimal cut-off of -50% for overall survival (OS) by recursive partitioning analysis. Deep immunoparesis (ARD ≤-50%) was associated with a higher tumour burden at first relapse compared to none/shallow [ARD >-50%] immunoparesis. The OS (P = 0·007) and progression-free survival (PFS; P < 0·001) differed significantly between the deep and none/shallow immunoparesis groups. Kaplan-Meier estimates for 3-year OS were 36% and 46%, and for 2-year PFS were 17% and 27%, respectively. On multivariable analysis (MVA) for PFS, both qualitative and quantitative immunoparesis retained negative prognostic impact independently. However, only quantitative immunoparesis was independently prognostic for OS on MVA. Depth of immunoparesis in relapsed MM is an important prognostic factor for post-relapse survival in the era of novel agents and continuous therapy.

Therapeutic Dose Monitoring of Busulfan Is Associated with Reduced Risk of Relapse in Non-Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplantation.

Optimal administration of busulfan (Bu) is hampered by variable and unpredictable drug metabolism in individual patients. At our institution, Bu was previously administered with fixed weight-based dosing (WBD) in combination with cyclophosphamide (Cy) and etoposide (E) for patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). In 2014, we adopted real-time pharmacokinetic (PK)-guided therapeutic drug monitoring (TDM) of Bu for all NHL patients undergoing Bu-containing ASCT. Here we compare outcomes of NHL patients who underwent ASCT with Bu/Cy/E using WBD and those who did so using TDM of Bu. We studied 336 consecutive adult NHL patients who underwent ASCT with Bu/Cy/E using WBD from January 2007 to December 2013 (n = 258) or TDM from May 2014 to December 2017 (n = 78), excluding patients with mantle cell lymphoma. Clinical outcomes, including relapse, nonrelapse mortality (NRM), progression-free survival (PFS), and overall survival (OS), hepatotoxicity and pulmonary toxicity were compared in the 2 groups. To adjust for differences in baseline characteristics between the groups, propensity-matched cohorts of WBD and TDM patients were also studied. After the first dose of Bu, the dose was increased in 36% of the patients and decreased in 41%. Changes in pulmonary and liver function from baseline to transplantation were not different between the 2 groups, although these changes showed significantly less variability with TDM than with WBD. Relapse was significantly lower and PFS was improved with TDM; 2-year estimates were 19% for TDM and 38% for WBD for relapse (P = .004) and 69% and 55%, respectively, for PFS (P = .038). No significant between-group differences in NRM or OS were seen. In multivariable analysis, TDM remained prognostic for lower risk of relapse (hazard ratio [HR], .52; 95% confidence interval [CI], .30 to .89; P = .018), but did not remain prognostic for PFS (HR, .74; 95% CI, .48 to 1.16; P = .19). Propensity-matched cohorts displayed similar patterns of outcomes. In subset analysis based on disease status at ASCT, TDM was associated with less relapse and better PFS than WBD for patients who underwent transplantation in less than complete remission (CR) compared with those who underwent transplantation in CR. Compared with WBD, PK-directed TDM of Bu reduces the incidence of relapse when used in combination with Cy and E for patients with NHL undergoing ASCT, particularly for patients in less than CR. These data support the continued use of personalized PK-guided dosing for all NHL patients undergoing ASCT with Bu-containing preparative regimens.

Progression with clinical features is associated with worse subsequent survival in multiple myeloma.

Response rate and survival in multiple myeloma (MM) has improved in the era of proteasome inhibitors and immunomodulatory drugs. However, most patients eventually relapse with biochemical progression (BP) alone or with clinical features of end-organ damage (CP: clinical progression), without or without extramedullary (EM) disease. We conducted a retrospective cohort study of 252 patients with MM experiencing first relapse (time, T0 ) to evaluate survival following CP with and without EM as a function of BP. Patients were divided into three groups: BP (n = 134; 53%), CP/EM- (n = 87; 35%) and CP/EM+ (n = 31; 12%). The median time from diagnosis to T0 was significantly shorter in CP/EM+ compared to CP/EM- and BP groups (13 vs 25 vs 25 months; P < 0.001). The incidence of abnormal metaphase cytogenetics at diagnosis was significantly higher in CP/EM+ compared to CP/EM- and BP groups (46% vs 18% vs 11% respectively; P < 0.001). At a median follow-up of 26 months from T0 , median overall survival was 50, 19 and 10 months for BP, CP/EM- and CP/EM+ groups, respectively (P < 0.001). On multivariable analysis, pattern of progression was a significant prognostic factor for OS (HR for CP/EM- vs BP: 3.6; CP/EM+ vs BP: 8.7 and CP/EM+ vs CP/EM-: 2.42; P < 0.001 for all comparisons), along with age at T0 . In conclusion, progression pattern is an important prognostic factor in the current era, with subsequent survival being dismal in patients with end-organ damage or EM disease at relapse. Clinical trials in relapsed MM should consider reporting patterns of progression at baseline to ensure balance between study arms.

Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma.

BACKGROUND: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n = 916), non-Hodgkin lymphoma (NHL; n = 3546) and plasma cell myeloma (PCM; n = 4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS. RESULTS: 335 MDS/AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR = 4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR = 2.5 [1.1, 2.5]); (2) ≥3 versus 1 line of chemotherapy for NHL (HR = 1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR = 2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort. CONCLUSIONS: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.

A phase I trial of bortezomib in combination with everolimus for treatment of relapsed/refractory non-Hodgkin lymphoma.

B-cell non-Hodgkin lymphomas (NHL) display dysregulation of pathways controlling cell proliferation and apoptosis. Combined proteasome and mTOR inhibition, demonstrated with bortezomib and everolimus in a preclinical model, thus warrants evaluation in humans. We conducted a phase I study to identify the maximum tolerated dose (MTD) and safety of this combination in relapsed/refractory (r/r) NHL. Twenty-nine patients were enrolled from July 2008 to March, 2015. Toxicities were primarily hematologic, and dose-limiting thrombocytopenia defined the MTD as 5 mg everolimus daily with 1.3 mg/m2 bortezomib d1, 4, 8, and 11 every 21 days. Of 25 response-evaluable patients there was one complete response in a patient with MCL and three partial responses (two MCL, one FL) for an overall response rate of 16%. In conclusion, the combination of everolimus and bortezomib results in dose limiting thrombocytopenia, but is tolerable. This combination has limited clinical activity in heavily pretreated NHL.

Efficacy of Standard Dose R-CHOP Alternating With R-HDAC Followed by Autologous Hematopoietic Cell Transplantation as Initial Therapy of Mantle Cell Lymphoma, a Single-Institution Experience.

BACKGROUND: Young fit patients with mantle cell lymphoma (MCL) are commonly treated with induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT). Induction regimens with modifications of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and/or incorporation of high-dose cytarabine (HDAC) appear more effective than R-CHOP alone. PATIENTS AND METHODS: We adopted a modification of the Nordic protocol using standard, rather than higher dose R-CHOP, alternating with HDAC (rituximab plus HDAC), for 3 cycles each or, for patients already treated with R-CHOP alone before referral for AHCT, an additional 2 cycles of rituximab plus HDAC. We herein report our experience with 28 patients treated with this regimen who proceeded to AHCT, and compare their outcomes with patients treated with either standard-dose R-CHOP (n = 38) or R-HCVAD/MA (cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate, and cytarabine; n = 21), before AHCT. RESULTS: With a median follow-up duration of 26 months, our data show that this modification of the Nordic regimen is a highly effective pre-AHCT first-line therapy for MCL (3-year progression-free and overall survival rates of 69% and 75%, respectively). CONCLUSION: By using a less intense induction, this regimen can serve as a platform for combined use of novel agents, with less risk of additive toxicity.

Grade 3 Follicular Lymphoma: Outcomes in the Rituximab Era.

BACKGROUND: Follicular lymphoma (FL) is heterogeneous. Although FL Grade 3B (FL3B) is treated as aggressive FL (aggFL), an optimal approach to FL Grade 3A (FL3A) remains unclear because few data exist on clinical outcomes on the basis of subclassification of FL Grade 3 (FL3) since the introduction of rituximab. We report outcomes of FL3 in the rituximab era. PATIENTS AND METHODS: We identified and analyzed a retrospective cohort of 53 patients with FL3A, 3B, and FL Grade 3 with areas of diffuse large B-cell lymphoma (DLBCL). They were divided into 2 groups: aggFL (n = 21) included patients with FL3B (n = 10) and FL3 (A or B) with concomitant DLBCL (n = 11); indolent lymphoma (n = 32) included only FL3A. RESULTS: Baseline characteristics did not differ between the groups. rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was initial treatment in 15 (79%) of patients with aggFL and 21 (72%) of those with FL3A; rituximab was included in initial therapy in 18 (95%) and 24 (83%), respectively. Comparing aggFL and FL3A, 5-year overall survival was 90% versus 79% (P = .97) and 5-year progression-free survival (PFS) 44% versus 34% (P = .75), respectively. CONCLUSION: We conclude that outcomes for FL3, primarily treated with R-CHOP, do not differ between FL3A and aggFL (FL3B and FL3/DLBCL). The aggFL group showed a plateau in PFS confirming these should be treated with curative intent. FL3A patients, mainly managed with R-CHOP, also show an apparent plateau in PFS. Although longer follow-up and confirmation in other data sets is required, this indicates potential undertreatment of FL3A with less aggressive regimens often used for indolent lymphoma.

Splenic marginal zone lymphoma: excellent outcomes in 64 patients treated in the rituximab era.

OBJECTIVES AND METHODS: Splenic marginal zone lymphoma (SMZL) is a rare non-Hodgkin lymphoma. We sought to identify prognostic factors and define outcomes in a cohort of 64 patients with SMZL who were treated at two large academic medical centers in North America in the rituximab era. RESULTS: Over a median follow-up of 37.8 (range 6-167.1) months, Kaplan-Meier estimate of median OS was 156.3 months and median PFS was 52.9 months. On univariate analysis, baseline hemoglobin <12 g/dl was associated with inferior OS (p = 0.045). High-risk FLIPI score was associated with inferior PFS when compared with intermediate/low risk (p = 0.05) and marginally significant with regard to OS (p = 0.056). Splenectomy was not predictive of OS or PFS (p = 0.563 and 0.937, respectively). Transformation to diffuse large B-cell lymphoma occurred in four (6.3%) patients during the observation period. OS was comparable to contemporaneous cohorts of patients with extranodal and nodal marginal lymphomas and FLIPI score was highly predictive for inferior PFS and OS when all three cohorts were analyzed together. CONCLUSION: Outcomes of SMZL, in our series, were excellent, with a median OS of >13 years. Low hemoglobin and high-risk FLIPI were associated with inferior outcomes.

Dual institution experience of nodal marginal zone lymphoma reveals excellent long-term outcomes in the rituximab era.

Nodal marginal zone lymphoma (NMZL) is a rare non-Hodgkin lymphoma that arises from mature B-cells. We delineate outcomes, prognostic factors and treatment trends among a large cohort of patients with NMZL in the rituximab era. We identified 56 such patients treated at our institutions. The majority presented with advanced stage disease (78·6%). Over a median follow-up of 38·2 months, median progression-free survival (PFS) was 42·4 months and median overall survival (OS) was not reached. Kaplan-Meier estimates of OS at 120 months after diagnosis was 71·9%. High-risk follicular lymphoma international prognostic index (FLIPI) was associated with inferior PFS. Age >60 years and elevated serum lactate dehydrogenase (LDH) were associated with inferior OS. Transformation to diffuse large B-cell lymphoma occurred in 7 patients, 6 of who presented with advanced disease. OS was comparable to our previously reported extranodal MZL cohort. FLIPI score predicted for inferior PFS and OS when both cohorts were analysed together (n = 267). In summary, outcomes in NMZL are favourable with a large majority of patients surviving at 120 months. High risk FLIPI, age >60 years, and elevated serum LDH were associated with inferior outcomes.

Is rituximab sub-optimally dosed in indolent B cell lymphoma?

Rituximab pharmacokinetics are affected by gender, age and weight and can affect outcomes in aggressive B cell lymphoma. Less is known about the pharmacokinetics of rituximab in indolent B cell lymphoma (iNHL). We analysed the effects of gender, age, weight and body surface area on the outcomes of 303 patients treated with first line rituximab-based regimens for iNHL. The patients were divided into 3 treatment cohorts: rituximab only, rituximab + chemotherapy (R-CTX) and R-CTX followed by rituximab maintenance; furthermore, each cohort was subdivided as follicular (FL) or non-FL, based on histology. Older males and patients with higher weight had worse outcomes when treated with R-CTX, probably due to faster rituximab clearance. Our results concur with studies of R-CTX for DLBCL. As this effect was not observed in patients treated with rituximab alone or R-CTX followed by rituximab maintenance, we hypothesize that higher rituximab levels reached with weekly rituximab and/or prolonged exposure achieved with maintenance therapy exceed the therapeutic threshold, even with faster clearance, which nullifies the negative effect of higher weight and male gender. In conclusion, under current practices, a subset of patients with iNHL, i.e., FL treated with R-CTX, may be sub-optimally dosed with rituximab.

Dual institution experience of extranodal marginal zone lymphoma reveals excellent long-term outcomes.

Extranodal marginal zone lymphoma (EMZL) is a B-cell lymphoma arising from mucosa-associated lymphoid tissue (MALT). The disease characteristics, clinical course and treatment vary considerably based on site of involvement. Because long-term outcome data for EMZL are limited, we sought to describe the clinical details of a large number of patients with EMZL evaluated at the Case Comprehensive Cancer Center over a 12-year period to identify prognostic markers including the impact of site of involvement. We identified 211 cases of EMZL involving the stomach (30%), ocular adnexa (19%), lungs (16%) and intestines (9%). Initial treatment included antibiotics (18%), radiation (21%), rituximab (20%), chemotherapy (3%), rituximab + chemotherapy (7%), surgery (17%) or observation (8%). After a median follow-up of 44·3 months (range 2·2-214·9), median progression-free survival (PFS) was 68·2 months (95% confidence interval [CI] 54·5-111·3) and median overall survival (OS) has not been reached. Age >60 years, elevated lactate dehydrogenase level (LDH), ≥4 lymph node groups involvement, and high follicular lymphoma international prognostic index (FLIPI) were associated with inferior PFS/OS. In summary, patients with EMZL have excellent prognosis with median OS in excess of 10 years. Age, elevated LDH, advanced disease, and high FLIPI score are associated with worse outcomes.

Host lymphocyte depletion as a strategy to facilitate early full donor chimerism after reduced-intensity allogeneic stem cell transplantation.

Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (RIC-alloHSCT) is associated with lower toxicity but higher rates of prolonged mixed chimerism than myeloablative conditioning. Decreased pretransplantation host T cell numbers are associated with less graft rejection and early full donor chimerism. To compensate for variability in pretransplantation host lymphocyte numbers and facilitate the achievement of rapid full donor chimerism, we tested a strategy of targeted lymphocyte depletion (TLD) using chemotherapy at conventional doses to provide cytoreduction and lymphocyte depletion before RIC-alloHSCT. In our study, 111 patients with advanced hematologic malignancies received 1 to 3 cycles of conventional-dose chemotherapy to reduce circulating lymphocytes to a predetermined level. Patients then underwent RIC-alloHSCT from HLA-matched siblings. Patients received a median of 2 cycles of TLD chemotherapy, resulting in a median 71% decline in CD4(+) count. All patients engrafted; there were no late graft failures. By day +14, median CD3(+) chimerism was 99% donor and was significantly associated with lower post-TLD CD4(+) counts (P = .012). One- and 5-year treatment-related mortality were 15% and 21%, respectively. At 1-year follow-up, 66% of patients had achieved complete remission (CR) of which 92% were not in CR at the time of transplantation. Overall survival at 1 and 5 years post transplantation were 66% and 47%, respectively.

Dose-adjusted EPOCH-rituximab combined with fludarabine provides an effective bridge to reduced-intensity allogeneic hematopoietic stem-cell transplantation in patients with lymphoid malignancies.

PURPOSE: There is currently no standard chemotherapy regimen for patients with lymphoid malignancies being considered for reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation (RIC-alloHSCT). The ideal regimen would provide disease control and result in lymphocyte depletion to facilitate engraftment. To this end, we developed a novel regimen by adding fludarabine to dose-adjusted continuous-infusion etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus with or without rituximab (DA-EPOCH-F/R). PATIENTS AND METHODS: One hundred forty-seven patients with lymphoid malignancy (median age, 50 years) who had heavily pretreated (median prior regimens, three) and chemo-refractory (47%) disease were treated with DA-EPOCH-F/R before RIC-alloHSCT. Patients received one to three consecutive cycles until achieving lymphocyte depletion (CD4(+) count < 200/µL) or progressive disease. RESULTS: Overall response rate was 41%; 39% of patients had stable disease. Toxicity included grade 4 neutropenia in 65% and thrombocytopenia in 25% of patients. DA-EPOCH-F/R resulted in lymphocyte depletion (P < .001), which was inversely associated with serum interleukin (IL) 7 and IL-15 levels. Of 147 patients, 143 patients proceeded to RIC-alloHSCT. Patients with lower CD3(+) (P < .001), CD4(+) (P < .001), and CD8(+) (P < .001) T-cell counts after DA-EPOCH-F/R were more likely to achieve full donor lymphoid chimerism by day +14 after transplant. Relative to nonresponders to DA-EPOCH-F/R, patients with complete and partial response had increased event-free survival (77.4 v 4.8 months; P < .001) and overall survival (98.5 v 16.2 months; P < .001). CONCLUSION: DA-EPOCH-F/R safely provides tumor cytoreduction and lymphocyte depletion, thereby offering a bridge to RIC-alloHSCT in patients with aggressive lymphoid malignancies.