Prognostic factors for advanced‐stage human immunodeficiency virus‐associated classical Hodgkin lymphoma treated with doxorubicin, bleomycin, vinblastine, and dacarbazine plus combined antiretroviral therapy: A multi‐institutional retrospective study
Jorge J. CastilloMark BowerJérémy BrühlmannUrban NovakHansjakob FurrerPaula Yurie TanakaCaroline BessonSilvia MontotoKate CwynarskiJeremy S. AbramsonSamir DaliaMichele BibasJoseph M. ConnorsMichael FurmanMinh‐Ly NguyenTimothy P. CooleyBrady BeltránJaime A. CollinsJulie M. VoseBlanca XicoyJosep‐María Ribera
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BACKGROUND The treatment and outcomes of patients with human immunodeficiency virus (HIV)‐associated Hodgkin lymphoma (HL) continue to evolve. The International Prognostic Score (IPS) is used to predict the survival of patients with advanced‐stage HL, but it has not been validated in patients with HIV infection. METHODS This was a multi‐institutional, retrospective study of 229 patients with HIV‐associated, advanced‐stage, classical HL who received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus combination antiretroviral therapy. Their clinical characteristics were presented descriptively, and multivariate analyses were performed to identify the factors that were predictive of response and prognostic of progression‐free survival (PFS) and overall survival (OS). RESULTS The overall and complete response rates to ABVD in patients with HIV‐associated HL were 91% and 83%, respectively. After a median follow‐up of 5 years, the 5‐year PFS and OS rates were 69% and 78%, respectively. In multivariate analyses, there was a trend toward an IPS score >3 as an adverse factor for PFS (hazard ratio [HR], 1.49; P =.15) and OS (HR, 1.84; P =.06). A cluster of differentiation 4 (CD4)‐positive (T‐helper) cell count <200 cells/μL was associated independently with both PFS (HR, 2.60; P =.002) and OS (HR, 2.04; P =.04). The CD4‐positive cell count was associated with an increased incidence of death from other causes (HR, 2.64; P =.04) but not with death from HL‐related causes (HR, 1.55; P =.32). CONCLUSIONS The current results indicate excellent response and survival rates in patients with HIV‐associated, advanced‐stage, classical HL who receive ABVD and combination antiretroviral therapy as well as the prognostic value of the CD4‐positive cell count at the time of lymphoma diagnosis for PFS and OS. Cancer 2015;121:423–431. © 2014 American Cancer Society .Keywords:
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Dacarbazine
ABVD
Brentuximab vedotin
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The H97-I trial (1997-2004) for Hodgkin lymphoma at intermediate stage (HL-I) included 269 patients who were randomized to receive three or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The 197 patients who reached complete remission (CR) (73.2%, p = 0.41 between arms) received radiotherapy (RT); their 10-year progression-free survival (PFS) rate was 87.7 ± 3.0%, similar to that of the 180 patients of a historical control group (HCG) in CR after three ABVD cycles before RT. The 59 patients who reached post-ABVD partial remission (PR) received one course of intensive chemotherapy (i.v., mg/m(2), vindesine 5, adriamycin 90, BCNU 140, etoposide 600, methylprednisolone 600) before RT. In spite of this additional intensive chemotherapy, their PFS rate (78.4 ± 6.3%) remained significantly lower (p = 0.03) than that of the 197 patients who reached post-ABVD CR, and was similar to that of the 60 patients of the HCG in PR after three ABVD cycles who did not receive additional chemotherapy before RT.
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It is unclear whether patients with early-stage Hodgkin's lymphoma and negative findings on positron-emission tomography (PET) after three cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) require radiotherapy.
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A pharmacokinetic study of anticancer drugs was carried out in 18 Hodgkin's lymphoma male patients. The anticancer drugs were administered to the patient by a standard procedure and a validated HPLC method was used for plasma concentration determination. Maximum plasma concentration (Cmax) of Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) were 7.71, 4.32, 7.95 and 6.51µg/ml respectively. Adriamycin and Dacarbazine exhibited longer Tmax compared to Bleomycin and Vinblastine. Area under the curve values of ABVD were 118.30, 82.11, 245.54 and 86.62µg/ml*h. The elimination rate constant of Dacarbazine was highest. Vinblastine exhibited highest half-life and mean residence time. Clearances of ABVD were 346.69, 2499.44, 45.90 and 5800.05ml/h. The apparent volume of distribution was highest for Dacarbazine and lowest for Vinblastine. The pharmacokinetic parameters can be utilized for monitoring of plasma concentrations, therapeutic drug monitoring and dosage adjustments to optimize anticancer efficacy in patients of Hodgkin's lymphoma.
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Extensive radiation therapy was the first therapeutic advance in the treatment of early-stage Hodgkin's lymphoma. More recently, less extensive radiation therapy in combination with chemotherapy has resulted in the lowest reported rates of early relapse. The HD10 trial (ClinicalTrials.gov number, NCT00265018) of the German Hodgkin Study Group showed that among patients with very favorable stage I or II Hodgkin's lymphoma, the outcome in those who received only two cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus involved-field radiation therapy in reduced doses was similar to the outcome in those who received four cycles of chemotherapy and involved-field . . .
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The JSH Practical Guidelines for Hematological Malignancies, 2018 expanded edition, newly adopted brentuximab vedotin, doxorubicin, vinblastine, dacarbazine(A+AVD)protocol as a standard treatment for advanced-stage classical Hodgkin lymphoma(CHL). Therefore, this retrospective analysis compared 15 patients who received A+AVD therapy with 21 patients who received doxorubicin, bleomycin, vinblastine, dacarbazine(ABVD)therapy. All patients were newly diagnosed with CHL and received induction therapy between April 2015 and June 2022 in our hospital. All except 1 patient of the A+AVD group had advanced-stage CHL. The median age was 63(23-85)years. The estimated 2-year overall survival of the A+AVD group was better than that of the ABVD group which included 6 patients with clinical stage Ⅲ or higher CHL (100% vs 66.7%, p=0.047). In contrast, there was no significant difference in the complete response rate(53.8% vs 100%, p=0.109)between the 2 groups. The overall response rate after first-line treatment(69.2% vs 100%, p=0.255), and the estimated 2-year progression-free survival(70.1% vs 66.7%, p=0.321)between the A+AVD and the ABVD groups were similar.
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Dacarbazine
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A cure rate of ≥90% for patients with early-stage Hodgkin lymphoma (HL) is routinely achieved with current regimens. But this success is tempered by the risk for late-onset morbidity and mortality associated with the initial treatment.
Previously, researchers conducted a multicenter, prospective, randomized, controlled trial to compare the use of 4 to 6 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or 35 Gy subtotal nodal irradiation (STNI) in newly diagnosed patients with nonbulky stage I or II HL …
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Hodgkin’s lymphoma (HL) is a type of cancer originating in the lymph nodes. The preferred therapy for advanced HL is a combination of chemotherapies including doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). ABVD has been standard therapy for advanced HL. It is generally considered as safe and rarely has been reported to cause acute liver failure. We present a case of 79-year-old woman with HL, who developed acute liver failure secondary to first cycle of ABVD chemotherapy.
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