Burkitt lymphomas failing dose-adjusted R-EPOCH (DA-R-EPOCH)

Dear Editor, Adults with Burkitt lymphoma/leukemia (BL) are usually treated with high-dose methotrexate-based chemotherapy and rituximab (R-HD-MTX)-containing regimens. While exact drug combinations and schedules vary, all contain HD-MTX and all result in similar outcomes [1–7]. Survival (OS) ranges from 70 to 90 % and treatment-related mortality (TRM) is 10–20 %. Recently, excellent results with doseadjusted R-EPOCH (DA-R-EPOCH) have been reported with 100 % OS and 0 % TRM [8]. We therefore tried DAR-EPOCH in patients with BL and high risk of complications but were unable to obtain comparable results. DA-R-EPOCH was administered in hospital in accordance with published guidelines [9]. HIV-infected patients were continued on highly active antiretroviral therapy (HAART). Our first patient was a 39-year-old woman admitted to another hospital. After 1 month, a diagnosis of BL stage IVB was made and the patient transferred to us. She was in poor condition with massive intra-abdominal disease, bone marrow infiltration, hypercalcemia, and kidney failure. One cycle of DA-R-EPOCH resulted in tumor regression. Blood counts normalized after 2 weeks, but pulmonary and neurological dysfunction progressed and she died within a month from multiorgan failure. The second patient was a 34-year-old man who presented with ophthalmoplegia. An epipharyngeal tumor and HIV infection were found. Diagnostic evaluation showed stage IVB BL with involvement of lymph nodes, epipharynx, liver, and bone marrow. He achieved complete remission (CR) after three DA-R-EPOCH cycles. Dose escalations were continued for five cycles, and a dose reduction was necessary in the sixth. The epipharynx was irradiated. Five months after the end of immunochemotherapy, he relapsed with a submandibular nodal mass. The patient received four cycles of our R-HD-MTX-based regimen [7], achieved CR, and was autografted. He is well and free of disease 3 months after transplantation and 18 months after diagnosis. The third patient was a 37-year-old man with AIDS responding to HAART. He had stage IVB BL with a large intra-abdominal mass, abdominal wall, and small bowel involvement. CR was achieved after three cycles of DA-REPOCH. Dose escalations were continued for four cycles. Two weeks after the end of sixth cycle, he relapsed with a large intra-abdominal mass. He failed to respond to multiple lines of chemotherapy, including our standard regimen, and radiotherapy and died 1 year after diagnosis. After this, we switched back to using R-HD-MTX in all patients with BL and did not have any failures since. Our limited experience with DA-R-EPOCH is different from the originally reported [8]. DA-R-EPOCH is less toxic and easier to administer than R-HD-MTX but might not be without TRM and as effective as described. These discrepancies are probably caused by differences in referral patterns. The first patient, who was referred too late, serves to illustrate that in such instances, toxic deaths will occur I. Aurer (*) : S. Basic-Kinda : I. Radman Division of Hematology, Department of Internal Medicine, University Hospital Centre Zagreb, Kispaticeva 12, 10000, Zagreb, Croatia e-mail: aurer@mef.hr