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Targeted therapies have largely replaced chemoimmunotherapy (CIT) in first-line treatment of chronic lymphocytic leukemia (CLL). We aimed to develop a prognostic model to determine who would benefit from first-line CIT vs target therapy. In follicular lymphoma, time from diagnosis to second treatment (TT2T) correlates better with overall survival (OS) than time from diagnosis to first treatment (TT1T). We hypothesized that TT2T is a potential surrogate for OS in CLL. In a model-building cohort (n = 298), we evaluated potential predictors for TT2T and derived a risk score, which we validated in an external cohort (n = 1141). Our data demonstrated that TT2T and OS were more strongly correlated than TT1T and OS. Our risk score model consisted of three predictors (unmutated IGHV, β2-microglobulin >297 nmol/L, and Rai stage I–IV), and was prognostic for TT2T and OS. TT2T is a promising surrogate for OS in CLL, but further validation is needed to establish this association. [ABSTRACT FROM AUTHOR]

The risk of TLS in patients with relapsed CLL treated outside of clinical trials is not well described. Using the Mayo Clinic CLL Database, 48 patients treated with venetoclax for relapsed CLL in routine practice were identified; chart review determined baseline risk for TLS and laboratory abnormalities during venetoclax ramp-up. Overall, 6 (13%) patients developed laboratory TLS, 3 of whom demonstrated clinical TLS. The majority of patients who developed TLS were stratified as low or medium risk by the package insert. Of the 42 patients who did not meet Howard criteria for TLS, isolated hyperphosphatemia occurred in 19 patients (45%), hyperkalemia in 13 patients (31%), hyperuricemia in 2 patients (5%), and hypocalcemia in 1 patient (2%). In routine practice, the incidence of TLS appears higher than reported in clinical trials (3–6%). Half of patients who did not meet criteria for TLS developed clinically significant electrolyte abnormalities that required medical intervention. [ABSTRACT FROM AUTHOR]

Anti-thymocyte globulin (ATG) has been associated with decreased rates graft versus host disease (GVHD) but with a potential risk of increasing risk of infection and relapse. We retrospectively studied the impact of single dose low dose (2.5 mg/kg) ATG in patients undergoing allogenic hematopoietic cell transplantation (HCT) from 8/8 matched unrelated donors (MUD). Of the total 209 patients identified, 129 received ATG. At baseline, the ATG group had more intermediate and high disease risk index (DRI) (64.6% vs. 54.3%) (28.3% vs. 23.7%) p <.001, respectively, and who received reduced intensity or non-myeloablative conditioning (RIC) (69.0% vs. 47.5%, p.003). There was no significant difference in the overall survival (OS) HR = 1.3, 95% CI [0.99, 1.0], p =.350 or relapse-free survival (RFS) HR = 1.2, 95% CI [0.74, 1.8], p =.526 between the two groups. Patients receiving ATG had a lower incidence of chronic GVHD (cGVHD) (10.1% vs. 25%, p =.007) and less moderate to severe cGVHD (8.5% vs. 25%, p =.002). ATG was associated with a reduced incidence of moderate to severe cGVHD OR = 0.28, 95% CI [0.12, 0.61], p <.01. There was no difference in the incidence of Epstein-Barr Virus (EBV) or cytomegalovirus (CMV) reactivation, CMV disease, invasive fungal infection, or grade III–IV acute GVHD (aGVHD). Our study shows that low dose ATG results in similar OS and RFS with lower rates of cGVHD. Additional prospective studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

We identified all patients with chronic lymphocytic leukemia at Mayo Clinic treated with ibrutinib outside the context of a clinical trial; timing and reasons for discontinuation were ascertained, as were symptoms, exam and radiographic findings, and laboratory changes following discontinuation. Of 202 patients who received ibrutinib, 52 discontinued therapy (estimated 1- and 2-year risk of discontinuation 18% and 28%, respectively). The most common reasons for discontinuation were toxicity (56%) and progression of disease (32%, including Richter's transformation in 15%). Rapid progression of disease within 4 weeks after discontinuation was observed in 9/36 (25%) patients with adequate records for review, mostly in those stopping ibrutinib for disease progression (n = 8) rather than toxicity (n = 1). This was evident by sudden worsening of disease-related symptoms (n = 9), exam/radiographic changes (n = 7), and laboratory changes (n = 8). An estimated one in every three patients discontinued ibrutinib by 2 years, with 25% developing rapid disease progression afterwards. [ABSTRACT FROM AUTHOR]

Therapeutic dose monitoring is widely adopted for determination of busulfan (Bu) dose for use as a conditioning regimen. However, while dose adjustments are being incorporated, transient fluctuations of Bu levels may occur. We aim to understand if these fluctuations affect clinical outcomes of these patients. We compared outcomes in patients in whom the absolute dose changes and fluctuation of AUC were ≥ median% versus < median%. Rates of sinusoidal obstructive syndrome, grades 2–4/grades 3–4 acute and chronic graft versus host disease were not different between the two cohorts. The Kaplan–Meier curves for overall survival showed no significant differences. Six patients required >50% dose adjustment and four had a fluctuation in AUC of >50%. One of these patients died of sinusoidal obstruction syndrome and two died of infections. In our study, the transient fluctuations in Bu levels did not affect clinical outcomes; hence obviating the need for test dose strategy. [ABSTRACT FROM AUTHOR]

Hematopoiesis that is fully genetically derived from donor is referred to as a complete donor chimerism (CC), whereas hematopoiesis with genetic origins from both donor and patient is referred to as a mixed chimerism (MC) [[3]]. For the 209 patients reviewed in this study, early chimerism lab testing costs alone were estimated to be more than $3,00,000 and this expense had no impact on patient outcomes. Donor lymphocyte infusions used to treat mixed-chimeric and high-risk patient populations in the relapsed and nonrelapsed settings after allogeneic transplantation for hematologic malignancies are associated with high five-year survival if persistent full donor chimerism is obtained or maintained. [Extracted from the article]

Epstein-Barr virus (EBV) reactivation is an unresolved medical issue after allogeneic hematopoietic stem cell transplantation (HSCT). Rituximab treatment is recommended for EBV reactivation after HSCT but the number of doses of rituximab to use is unclear. In this study, risk factors and outcomes of patients who needed 1 dose vs >1 doses of preemptive rituximab to clear EBV viremia were compared. A higher viral load was more likely to be associated with higher doses of rituximab. Patients whose EBV viremia cleared with 1 dose of rituximab were more likely to have a preceding reduction of immunosuppression. Overall survival (OS) in these 2 cohorts was not different (18.7 vs 26.6 months, respectively, p = .96). Since rituximab can have side effects and is fairly costly, a predictive model to determine the number of rituximab doses using viral load would be a useful and cost-effective manner to utilize rituximab for this indication. [ABSTRACT FROM AUTHOR]

In this phase 2 trial, we sought to evaluate the efficacy and safety of rituximab, cyclophosphamide, bortezomib, and dexamethasone (R-CyBorD) in patients with low-grade NHL. The regimen included rituximab on day 1 with weekly cyclophosphamide, dexamethasone, and bortezomib 1.3 mg/m2 IV in a 28-day cycle. Twenty one patients were enrolled on the study. Median age was 69 years (range 51-80) and 17 (81%) patients had two or more prior treatments. Histologies included FL (n = 8), MCL (n = 8), and LPL/WM (n = 5). Hematologic toxicity and peripheral sensory neuropathy were the most common adverse events. With a median follow-up of 38.1 months, ORR was 13/21 (62%), with 4 (19%) CR. The ORR was 7/8 (88%) in FL and was 4/5 (80%) in LPL/WM. Median PFS and OS were 11.6 months and 54.8 months, respectively. R-CyBorD is an effective regimen in relapsed FL and LPL/WM patients with an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Disparities in outcomes after hematopoietic cell transplant (HCT) are reported mostly by registry studies. We examined the association of self-reported race and ethnicity with outcomes and health care utilization after allogeneic HCT in a single center study. Clinical and socioeconomic data of 296 adult patients who underwent allogeneic HCT from November 2003 to October 2012 were analyzed. Survival was compared between non-Hispanic Whites (NHW) and minority patients using Cox proportional hazards regression. Some 73% of patients were NHW and 27% were racial/ethnic minority patients. More minority patients were younger and had lower socioeconomic status. Both unadjusted and adjusted overall and progression-free survival were comparable between the two groups. High risk disease, poor performance score and Medicare/Tricare were significant predictors of mortality. Health care utilization was comparable between the two groups. Homogeneity of medical care for allogeneic HCT may help overcome racial/ethnic disparities, but not those due to patients' primary insurance. [ABSTRACT FROM AUTHOR]

High-dose therapy with autologous stem cell transplant (autoSCT) is standard therapy for relapsed/refractory Hodgkin lymphoma, although the optimal conditioning regimen remains uncertain. We conducted a retrospective analysis of 100 consecutive patients with relapsed/refractory Hodgkin lymphoma who underwent autoSCT between 1998 and 2009. There were 60 patients who received busulfan, melphalan and thiotepa (BuMelTt) conditioning and 40 who received other common regimens. There were no significant differences in patient characteristics between the two groups. With a median follow-up of 4.3 years, the 5-year overall survival (OS) was superior for patients who received BuMelTt versus other conditioning (73% vs. 44%, p = 0.05). BuMelTt was also associated with an improved 5-year progression-free survival (66% vs. 37%, p = 0.03). There were no differences in length of hospitalization, febrile neutropenia, hepatic veno-occlusive disease or 100-day non-relapse mortality (NRM). There were more cases of severe mucositis but fewer episodes of bacteremia with BuMelTt. Our results suggest that BuMelTt may be a superior conditioning regimen for autoSCT in Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

Thirty-three previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) were treated before meeting standard criteria with alemtuzumab and rituximab. Granulocyte macrophage colony stimulating factor (GM-CSF) was added to the regimen to determine whether it would improve treatment efficacy without increasing toxicity. High risk was defined as at least one of the following: 17p13−; 11q22.3−; unmutated IGHV (or use of VH3-21) together with elevated expression of ZAP-70 and/or CD38. Treatment was subcutaneous GM-CSF 250 μg Monday-Wednesday-Friday for 6 weeks from day 1, subcutaneous alemtuzumab 3 mg-10 mg-30 mg from day 3 and then 30 mg Monday-Wednesday-Friday for 4 weeks, and intravenous rituximab (375 mg/m2/week) for 4 weeks from day 8. Patients received standard supportive care and were monitored weekly for cytomegalovirus (CMV) reactivation. Using standard criteria, 31 (94%) patients responded to treatment, with nine (27%) complete responses (one with persistent cytopenia) and nine (27%) nodular partial responses. Median progression-free survival was 13.0 months and time to next treatment was 33.5 months. No patient died during treatment, seven (21%) had grade 3-4 toxicities attributable to treatment, and 10 (30%) had CMV viremia. Addition of GM-CSF to therapy with alemtuzumab and rituximab decreased treatment efficacy and increased the rate of CMV reactivation compared to a historical control. [ABSTRACT FROM AUTHOR]

Isolated central nervous system (CNS) relapse occurred in 5 out of 24 patients (20.8%) with chronic myeloid leukemia (CML) lymphoid blast crisis (2), Philadelphia (Ph) chromosome positive acute lymphoblastic leukemia (ALL) (2) or CML with biphenotypic markers (1) treated on imatinib mesylate (IM) protocols at our institution. CNS relapse occurred despite peripheral blood (5) and bone marrow (3) complete responses. Median time to CNS relapse was day 32 (range 23 to 100). This observation raised the possibility that IM may not penetrate into the CNS. Simultaneous plasma and cerebral spinal fluid (CSF) IM levels were determined in four subsequent patients by liquid chromatography and mass spectrophotometric assay. Levels of IM were found to be approximately two logs lower in CSF than in plasma (0.044 μg/ml (0.088 ± 0.029 μM) vs 3.27 μg/ml (6.54 ± 0.93 μM)). CSF levels were substantially below the concentration required for inhibition of BCR-ABL and killing of cell lines in vitro . These results suggest that IM may not penetrate the intact blood/brain barrier and its implications are discussed. [ABSTRACT FROM AUTHOR]