Impact of intended and relative dose intensity of R-CHOP in a large, consecutive cohort of elderly diffuse large B-cell lymphoma patients treated with curative intent: no difference in cumulative incidence of relapse comparing patients by age.

BACKGROUND: The increasing incidence of diffuse large B-cell lymphoma (DLBCL) in ageing populations places a significant burden on healthcare systems. Co-morbidity, frailty, and reduced organ and physiological reserve contribute to treatment-related complications. The optimal dose intensity of R-CHOP to optimize outcome across different ages with variable frailty and comorbidity burden is unclear. OBJECTIVES AND METHODS: We examined the influence of intended (IDI) and relative (RDI) dose intensity of the combination of cyclophosphamide and doxorubicin, age and comorbidity on outcomes for DLBCL patients ≥70 years in a representative, consecutive cohort across eight UK centres (2009-2018). We determined predictors of survival using multivariable Cox regression, and predictors of recurrence before death using competing risks regression. RESULTS: Porgression-free survival (PFS) and overall survival (OS) were significantly inferior in patients ≥80 vs. 70-79 years (P < 0.001). In contrast, 2-year cumulative relapse incidence, when accounting for non-relapse mortality as a competing risk, was no different between 70-79 vs. ≥80 years (P = 0.27) or comorbidity status (CIRS-G: 0-6 vs. >6) (P = 0.27). In 70-79 years, patients with an IDI ≥80% had a significantly improved PFS and OS (P < 0.001) compared to IDI < 80%. Conversely, in patients ≥80 years, there was no difference in PFS (P = 0.88) or OS (P = 0.75) according to IDI <80% vs. ≥80%. On multivariable analysis, when comparing by age, there was a significantly higher cumulative relapse rate for patients aged 70-79 years with an IDI <80% (vs. >80%) (P = 0.04) but not for patients ≥80 years comparing IDI (P = 0.32). CONCLUSION: 'R-mini-CHOP' provides adequate lymphoma-specific disease control and represents a reasonable treatment option in elderly patients ≥80 years aiming for cure.

Outcome in patients with diffuse large B-cell lymphoma who relapse after autologous stem cell transplantation and receive active therapy. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT).

Autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who relapse/progress after first line chemoimmunotherapy. Long-term outcome of those who relapse after transplant is poor. We present the results of a retrospective study of 256 adult patients reported to the EBMT registry with DLBCL who relapsed after auto-HSCT performed between 2003 and 2013, and who received active salvage strategies. One hundred and fifty-four (60%) were male; median age was 53 years. Median time to relapse was 7 months, 65% relapsed during the first year. Overall response rate after salvage therapy was 46%. Median follow-up after first salvage therapy was 40 months (IQR 23-63 months). Overall survival (OS) at 3 years was 27% (95% CI 22-33). OS at 3 years of patients relapsing longer than 1 year after auto-HSCT was 41% (95% CI 31-53) compared with 20% (95% CI 14-24) in those who relapsed in less than 1 year. Eighty-two patients (32%) had a second HSCT, an allogeneic HSCT (allo-HSCT) in 69 cases, at a median time of 6.5 months after relapse. OS at 3 years after allo-HSCT was 36% (95% CI 25-51). In conclusion, the prognosis of patients with DLBCL that relapse after auto-HSCT is dismal. Patients who relapse in less than 1 year remain an unmet need, and should be considered for CAR T cell therapy or clinical trials. Patients who relapse after 1 year can be rescued with salvage therapies and a second HSCT. These results provide a benchmark to compare data of new prospective studies.

IVE (ifosfamide, epirubicin and etoposide) is a more effective stem cell mobilisation regimen than ICE (ifosphamide, carboplatin and etoposide) in the context of salvage therapy for lymphoma.

Two commonly used chemotherapy regimens for lymphoma salvage therapy were compared: ICE (ifosphamide, carboplatin and etoposide) +/- rituximab and IVE (ifosfamide, epirubicin and etoposide) +/- rituximab, for their efficacy in mobilising peripheral blood stem cells for autologous transplantation. Significant differences were observed between the cohorts in terms of number of patients mobilising the stipulated minimum >2 x 10(6) CD34+/kg (99.2% in IVE group versus 83% in ICE group: P = 0.0002) and also in terms of the number of patients achieving the predetermined target of >5 x 10(6) CD34+/kg, both in total and during the first apheresis procedure (72% in IVE versus 51% in ICE group and 49% in IVE versus 7% in ICE group: P = 0.02 and P < 0.0001 respectively). This analysis of two similar groups of patients treated within a single-centre appears to demonstrate that the IVE regimen is a more effective stem cell mobilisation regimen than ICE in the context of salvage therapy for Hodgkin and non-Hodgkin lymphoma, allowing more patients to achieve the target CD34+ cell collection and proceed to high-dose therapy and autologous stem cell transplantation.

Repeat treatment with iodine-131-rituximab is safe and effective in patients with relapsed indolent B-cell non-Hodgkin's lymphoma who had previously responded to iodine-131-rituximab.

BACKGROUND: Small series suggest retreatment of indolent lymphomas with murine anti-CD20 radioimmunotherapy is effective. The longer half-life of iodine-131 ((131)I)-rituximab may result in increased bone marrow exposure, with greater toxicity on repeat administration. We examined the effects of a second (131)I-rituximab in patients with indolent lymphoma following relapse. PATIENTS AND METHODS: We analyzed two institutional databases from January 2000 to July 2007 for retreatment with (131)I-rituximab. The severity of cytopenia, development of myelodysplasia (MDS), acute myeloid leukemia (AML) and hypothyroidism was noted. We compared response duration and toxicity of the treatments. RESULTS: Fourteen of 16 patients responded with nine complete responses (CRs), with a median duration of 10.5 months in responders. Six of 13 reresponders had the same or a longer response and six more remain in complete response. The median event-free survival was not significantly different for the two treatments. There was no significant difference in the severity of myelosuppression. Four patients developed hypothyroidism with three requiring thyroxine. One patient developed AML, with no other cases of MDS. The actuarial progression-free survival rate at 12 months was 36%. CONCLUSIONS: Repeat (131)I-rituximab induces high response rates, some of which result in durable remissions in patients who had previously responded.

High dose melphalan or intermediate dose melphalan can be well tolerated and result in good response rates in selected elderly patients with myeloma.

We have used two strategies for treating myeloma patients aged 65-75 years. Those fit enough underwent Cyclophosphamide mobilisation and PBSCT using melphalan 200mg/m(2) (HDM) (n=15, median 67 years). Those less fit were mobilised with G-CSF and received melphalan 70mg/m(2) (IDM) (n=15, median 69 years). Where possible sufficient PBSC were collected so that patients not in CR after their first IDM, underwent a second IDM procedure (n=6). The treatment was well tolerated with zero day+100 TRM. Median cell dose was 4.85x10(6)CD34+cells/kg and 2.7x10(6) in the HDM and IDM groups, respectively. Neutrophil engraftment was faster in the HDM group but despite this there was a trend to earlier discharge in the IDM group (13 days versus 15 days) and lower antibiotic and anti-fungal usage, suggesting better tolerability. Response rates were similar with CRs achieved in 7/15 patients receiving HDM and 9/15 receiving IDM (6 after the first and 3 after the second procedure). Three patients did not undergo a second IDM due to insufficient cells. In the IDM group 11/15 remain alive at a median follow up of 14 months with 5 in CR, whilst in the HDM group 12/15 are alive with 5 in CR at a median follow up of 15.5m. We conclude both approaches have comparable efficacy but that IDM may be better tolerated in an older age group.

The role of granulocyte transfusions in neutropenic patients.

The precise role for donor granulocyte infusions remains to be delineated, partly because of the lack of defined clinical trials. The aim of this article is to summarize the studies undertaken so far and highlight the logistical problems associated with undertaking future studies. We also aim to provide a practical guide to the application of this therapeutic approach.