The adjuvant role of low dose total body irradiation following chemoimmunotherapy in elderly high risk patients with diffuse large B-cell lymphoma (DLBCL)
Journal of Clinical Oncology(2006)
Abstract
17523 Background: Results from the RICOVER-60 trial indicated a better outcome in elderly DLBCL patients (pts) by adding rituximab (R) to CHOP and shortening cycle intervals 14 days. We tested the addition of low dose total body irradiation (LTBI) to what proved to be the best performing arm of the RICOVER-60 trial (6xR-CHOP-14 + 2xR). Methods: A phase II trial including pts>60 yrs with stage II-IV, CD20-positive DLBCL was started in 2003 and is still ongoing. Pts received 6x R-CHOP-14 and 2 x R alone followed by LTBI given as 2 courses of 4 daily fractions of 0,2 Gy separated by 2 weeks of rest. Subpopulations of blood lymphocytes, monoctytes and dendritic cells were identified by multi-color flowcytometry during treatment. Results: 24 patients finished their treatment and were found to be predominantly high risk. Median age was 68 years; 50% had ≥ 1 extranodal lesion; 71% had stage III or IV; 63% had B symptoms; 58% had ECOG score ≥ 1; 75% had elevated LDH and 58% had IPI of >2. There were 3 toxic deaths (12.5%) due to sepsis occurring after 1st, 3rd and 5th chemotherapy cycle, respectively. One patient got off study because of disease progression. 14 pts achieved a CR or CRu at the end of chemotherapy, while 6 were in PR. After LTBI, all 6 PR pts converted to CR. 3 pts relapsed within 7 months after achieving CR. All treatment failures occurred in patients with IPI 3&4. 94%, 100% and 98% of the administered R-CHOP-14, Rituximab and LTBI cycles respectively were given in full dose and on time. CTC Gr 3–4 neutropenia occurred following 22 of 135 R-CHOP-14 cycles (16%). CTC Gr. 3–4 thrombocytopenia was seen in 4 pts following the last LTBI cycle (16%). Preliminary data from multi-color flowcytometry of the first seven pts, showed depletion of circulating B-cells, but in some pts, a relative increase in the frequency of circulating dendritic cells during chemotherapy, which was enhanced by LTBI. Conclusion: In high-risk elderly DLBCL pts, R-CHOP-14 is associated with potential fatal infections. LTBI adds relatively little extra toxicities in the form of thrombocytopenia and may have the potential of converting PR patients to CR. Testing lymphocytic subpopulations in peripheral blood may help elucidating the immunomodulatory mechanisms of LTBI. No significant financial relationships to disclose.
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Key words
chemoimmunotherapy,total body irradiation,low dose,elderly high risk patients,b-cell
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