ABVD remains a standard chemotherapy for Hodgkin Lymphoma (HL) despite many efforts to demonstrate the superiority of other regimens. Bleomycin was proven marginally active in this combination (J Clin Oncol 22:1532-3, 2004) but adding significant toxicity. Response to ABVD is often slow and relapse rate of 20-30% is a concern. ABVD has never been directly compared to CHOP, the other global standard for other lymphomas that is composed of agents certainly active in HL. Current study is an update on our initial report of 2004 (Blood 104, 2004). In addition to extending the follow-up, we compared outcome after CHOP in a pilot series of previously untreated patients with a retrospective results of ABVD therapy at our institution. CR/CRu rates were 88 and 62% for CHOP and ABVD, respectively. In CHOP CS III/IV group, more patients had at least three risk factors (80%) than in ABVD CS III-IV group (40%). In contrast to ABVD, there were no deaths in CHOP group, but EFS was inferior. This might result from a higher risk level in CHOP patients. Toxicity of both regimens was mild: grade 3/4 leukopenia in 9%, grade 1/2/3 peripheral neuropathy in 6% of ABVD patients, and grade 3/4 neutropenia in 7% of CHOP patients. In conclusion, CHOP-21 is an active and low-toxic regimen in HL with risk factors. A prospective comparison of CHOP with a standard chemotherapy in a randomized study will be justified.

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Chemotherapy for Hodgkin’s Lymphoma (HL), universally regarded as a standard, i.e. ABVD, is not a perfect combination. Bleomycin was proven marginally active (J Clin Oncol2004;22:1532) but more or less toxic in majority of patients (skin, lung toxicity, and pyrexia). There is no convincing evidence of any positive role of Dacarbazine (DIC) in HL, but again its toxicity (hematologic, nausea and vomiting) is remarkable. Recent report on molecular effects of DIC on melanoma cells leading to selection of cells with more aggressive phenotype raised new safety concerns (J Clin Oncol2004;22:2092). Schedule of ABVD regimen requires more frequent patient visits than usual outpatient chemotherapy and a number of i.v. infusions is increased. Response to ABVD is often slow and relapse rate of 20–30% is a concern. ABVD remains a standard because it has been proven superior to MOPP and up to now, there is no clear evidence of superiority of any other regimen. ABVD has not been directly compared to CHOP - the other global standard for different lymphoma type, composed of agents unequivocally active in HL. In addition, early and late toxicity of CHOP appears rather modest and acceptable. In the current study we evaluated response, progression free survival (PFS), and early toxicity of CHOP chemotherapy in HL patients who failed to initial ABVD treatment (n=17) or in untreated patients with unfavorable or advanced disease (n=20). Eligibilty included: progressive disease (PD) on ABVD (n=2), slow response to ABVD, i.e. no PR after 2 cycles (n=7), and grade 3 or 4 toxicity (n=8). For untreated disease: stage 3 or 4 (n=5), early stage (n=15) with bulky lesion and/or presence of 2 or more adverse prognostic factors (N Eng J Med1998;339:1506). Patient characteristics: median age (range) - 29 (19–59), male sex - 62%, B symptoms - 84%, stage 3/4 – 32%, number of sites > 3 – 86%, E sites - 38%, bulk -73%, LDH>N - 68%, albumin <4g/dl - 84% of patients. Median number of prior ABVD cycels (range) - 2 (0.5–6). Median (range) of CHOP courses - 6 (2–8). Involved or mantle field radiotherapy (RT) was given to 65% of pts who had initial bulky mediastinum or no CR. Of 35 patients evaluable for response to CHOP, 11 (31%) achieved CR and 23 (66%) - CRu. Conversion to CR following RT was seen in 50% of pts. (11/22). After a median follow up of 21 months 4 pts. had PD or relapse (11%). One patient was diagnosed with laryngeal cancer 2 months after the end of treatment and died from cancer after 14 months. PFS was 87% (95% C.I.=[69%, 95%]) and it was similar in RT and no-RT pts. (p=0.81). There was no clinically significant toxicity and no cardiac abnormalities on ultrasonography after CHOP. Two patients developed gynecomastia due to testicular dysfunction. In conclusion, CHOP was well tolerated and resulted in 97% of CR/CRu in unfavorable or advanced HL with early relapse rate of 11%. These results may support considering a comparative study of CHOP vs ABVD. Figure Figure

Hodgkin lymphoma (HL) and diffuse large B cell lymphoma (DLBCL) represent 15% and 20%, respectively, of all lymphoma types. The aim of this study was to identify and compare circulating serum miRNA (c-miRNA) and peripheral whole blood miRNA (wb-miRNA) profiles in patients with these lymphomas. Serum samples (20 HL, 21 DLBCL, and 30 healthy controls) and whole blood samples (21 HL, 17 DLBCL patients, and 30 healthy controls) were collected at the time of diagnosis. Serum and whole blood were also collected from 18 HL/17 DLBCL and eight HL/nine DLBCL patients, respectively, after treatment. Pairwise comparisons identified 125 c-miRNAs (adjusted P value < 0.05) showing significant dysregulation between 30 healthy controls and patients; of these, 47 and 55 differentiated controls from pretherapeutic HL and DLBCL patients, respectively. In addition, 60 and 16 c-miRNAs differentiated controls from posttherapeutic HL and DLBCL, respectively. Pairwise comparisons identified 292 wb-miRNAs (adjusted P value < 0.05) showing significant dysregulation between 30 controls and patients; of these, 103 and 169 differentiated controls from pretherapeutic HL and DLBCL, respectively, and 142 and 151 wb-miRNAs differentiated controls from posttherapeutic HL and DLBCL, respectively. Thus, lymphoma-associated miRNAs may be a better source of noninvasive candidate biomarkers than miRNAs in serum. It is unclear whether miRNA alterations in lymphoma cells are similar to those observed in white blood cells.