Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin's lymphoma autografted after a first relapse

Sureda, Anna; Constans, Mireia; Iriondo, A; Arranz, Reyes; Caballero, Marı́a Dolores; Vidal, María-Jesús; Petit, J; López, Ángel L.; Lahuerta, Juan José; Carreras, Enric; Garcı́a-Conde, J; García-Laraña, José; Cabrera, Rafael; Jarque, Isidro; Carrera, Dolores; García‐Ruiz, Juan Carlos; Pascual, María José; Rifón, J.; Moraleda, José Marı́a; Perez-Equiza, Katy; Albó, Carmen; Dı́az-Mediavilla, Joaquı́n; Torres, Antonio; Torres, Pio; Besalduch, Juan; Marı́n, Jesús; Mateos, M. V.; Fernández-Rañada, J M; Sierra, Jorge; Conde, Eulogio

doi:10.1093/annonc/mdi119

Cited by 208 publications

(169 citation statements)

References 28 publications

(37 reference statements)

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“…Approximately 50% with chemosensitive relapse, defined as a partial remission or complete remission to salvage therapy, will have a durable remission following this intervention as compared to 20% with stable disease or a minor response to salvage chemotherapy [69], [70] and [71]. To date no randomised trials have compared the effectiveness of salvage regimens.…”

Section: Relapsementioning

confidence: 99%

Human immunodeficiency and Hodgkin lymphoma

Sissolak

Jacobs

2010

Transfusion and Apheresis Science

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Presentation of Hodgkin lymphoma (HL) is distinctive in the infected individual being more advanced, accompanied by B symptoms and the presence of extranodal disease particularly lymphadenopathy of the head and neck. Bone marrow involvement may be found in over 50% of cases. Virtually all co express gamma-herpesvirus. Phenotypically there is prominence of the mixed-cellularity and lymphocyte depleted histopathologic subtypes that define an aggressive clinical course in comparison to other variants. Prior to the induction of cART, median survival was only 1-2 years. Notably the first chemotherapy trial using ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in 21 patients, without treating the viral infection, resulted in a 43% complete remission rate accompanied by severe haematological toxicities but did not extend median survival with this being 1.5 years matching the negative cases.Significant change accompanied concomitant anti-retroviral therapy that could be given safely even with dose intensive regimens exemplified by BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in 12 patients or the Stanford V regimen (doxorubicin, vinblastine, mechlorethamine, etoposide, vincristine, bleomycin, prednisone) coupled with involved-field radiation for bulky disease studied in 59 patients. BEACOPP extended overall survival (OS) to 83% at 2 years. A similar trend was seen 1 when using the Stanford V regimen with an OS rate of 51% at 3 years, disease-free survival (DFS) of 68% and freedom from progression (FFP) in 60%. Additional benefits accrued from supportive care with stimulatory peptides such as G-CSF and when combined with bacterial prophylaxis results approached that found in the uninfected reference group. Current consensus holds this particular lymphoma as still among the non-AIDS defining cancers being lung, stomach, liver or anal despite these having recently gained more attention as several of these neoplasms may be occurring more commonly in the era of cART.While the relative risk of developing a non-AIDS-defining neoplasm in HIV-infected persons on the average is 2-3 times, the risk for developing HL in HIV-infected cases impressively ranges between 5 and 25 times when compared to the general population. Based on the precedent in which Kaposi sarcoma and the non-Hodgkin lymphomas distinctively alter the course of this retroviral infection in a way indistinguishable from concurrent Hodgkin lymphoma we propose that this entity be similarly regarded and the hypothesis tested in large randomised prospective study.

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Section: Relapsementioning

confidence: 99%

Human immunodeficiency and Hodgkin lymphoma

Sissolak

Jacobs

2010

Transfusion and Apheresis Science

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“…18 Transplant-related prognostic factors such as chemotherapy sensitivity, disease status at auto-HSCT, Karnofsky performance status (KPS) at the time of transplant, number of pre-transplant chemotherapy regimens and extranodal disease have been reported to predict which patients are likely to benefit most from auto-HSCT. 8,[19][20][21][22][23] However, disease recurrence post transplant remains the single major cause of treatment failure. 24 Classical cyclophosphamide, carmustine (BCNU) and etoposide (CBV) combination is a standard conditioning regimen prior to auto-HSCT for patients with HL.…”

Section: Introductionmentioning

confidence: 99%

“…Many modifications of the CBV regimen have been employed with varying results. 8,19,[21][22][23][24][25][26][27][28] In an attempt to decrease recurrence rates, more intense conditioning regimens have yielded better responses albeit at the cost of increased toxicity. 21,23,25 We report our single-institution experience of an intensified VCB conditioning regimen with a unique dosing schedule of infusional etoposide, bolus cyclophosphamide and higher dose BCNU sequentially followed by auto-HSCT in the treatment of relapsed or refractory HL.…”

Section: Introductionmentioning

confidence: 99%

Intensive conditioning regimen of etoposide (VP-16), cyclophosphamide and carmustine (VCB) followed by autologous hematopoietic stem cell transplantation for relapsed and refractory Hodgkin's lymphoma

Benekli

Smiley

Younis

et al. 2007

Bone Marrow Transplant

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Several high-dose therapy regimens are used for autologous hematopoietic stem cell transplantation (auto-HSCT) for relapsed and refractory Hodgkin's lymphoma (HL) with variable disease response. An intensified regimen of etoposide (VP-16) 2400 mg/m 2 , cyclophosphamide 7200 mg/m 2 and carmustine (BCNU) 600 mg/ m 2 (VCB) pre-auto-HSCT was developed to overcome disease recurrence. A total of 43 relapsed and refractory HL patients underwent auto-HSCT between January 1992 and December 2004. At day 100 there were 37 (86%) complete responses. A total of 40 patients survived beyond day 100, 14 of whom subsequently relapsed/ progressed. At a median follow-up of 4.9 years (range 1.5-11.4 years), 26 patients (60%) are alive and disease free. Five-year actuarial event-free survival (EFS) was 53% (95% CI 35-70%) and median EFS was 5.9 years. Median progression-free and overall survivals have not been reached. EFS was reduced with an increasing number of prognostic factors (Karnofsky performance status, KPS o90, chemotherapy-resistant disease and X3 chemotherapy regimens prior to transplant p1 vs X2; P ¼ 0.049). Grade III-IV regimen-related toxicity was 9% (n ¼ 4). The 1-year cumulative incidence of interstitial pneumonitis (IP) was 36%, however only two patients died of IP complications. Disease progression was the most common cause of death (n ¼ 10, 23%). Intensive VCB is an effective and well-tolerated preparative regimen for relapsed and refractory HL auto-HSCT.

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“…Unfortunately, ASCT is only effective in approximately 50% of such patients. 3,4 Among those who have a relapse after ASCT, overall survival is 55% at 2 years and 32% at 5 years. 5 Because the incidence of Hodgkin's lymphoma peaks during young adulthood, these premature deaths have a substantial social impact.…”

mentioning

confidence: 99%