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, Mustafa; Smiley, Shannon; Younis, Tallal; Czuczman, Myron S.; Hernandez‐Ilizaliturri, Francisco J.; Bambach, Barbara; Battiwalla, Minoo; Padmanabhan, Swami; McCarthy, Philip L.; Hahn, Theresa

doi:10.1038/sj.bmt.1705951

Cited by 28 publications

(13 citation statements)

References 46 publications

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“…High-dose chemotherapy followed by hematopoietic stem cell transplantation is associated with an inherent risk of pneumonitis, even in the absence of thoracic RT [29, 30]. However, when peri-transplant RT is administered, the risk of pneumonitis increases, as shown in several studies [14, 31–33].…”

Section: Discussionmentioning

confidence: 99%

Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

Pinnix¹,

Smith²,

Milgrom³

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

122

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Purpose Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Methods We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP per the Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ2 test and logistic multivariate regression. Results Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grade 1–3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation (10%, P=0.019). Several dosimetric parameters predicted RP, including mean lung dose (MLD) >13.5 Gy, V20 >30%, V15 >35%, V10 >40% and V5>55%. The likelihood ratio (LR) χ2 value was highest for V5< 55% (LR χ2=19.37). Conclusions In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed or refractory lymphoma who received salvage chemotherapy and hematopoietic stem cell transplantation were at higher risk for symptomatic RP.

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Section: Discussionmentioning

confidence: 99%

Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

Pinnix¹,

Smith²,

Milgrom³

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

122

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“…Prior studies showed that higher doses of BCNU increase risk of pulmonary toxicity as high as 35% [56,57]. In an effort to reduce pulmonary toxicity, Arai et al (2010) conducted a phase I/II study of conditioning regimen using gemcitabine along with vinorelbine (gemcitabine maximum tolerated dose 1250 mg/m2) [58].…”

Section: Introductionmentioning

confidence: 99%

A Review of Autologous Stem Cell Transplantation in Lymphoma

Zahid

Akbar

Amaraneni

et al. 2017

Curr Hematol Malig Rep

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Purpose of review Chemotherapy remains the first line therapy for aggressive lymphomas. However, 20–30% of patients with non-Hodgkin lymphoma (NHL) and 15% with Hodgkin Lymphoma (HL) recur after initial therapy. We want to explore the role of high dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) for these patients. Recent findings There is some utility of upfront consolidation for high risk/high grade B cell lymphoma, mantle cell lymphoma and T cell lymphoma but there is no role of similar intervention for HL. New conditioning regimens are being investigated which have demonstrated an improved safety profile without compromising the myeloablative efficiency for relapsed or refractory HL. Summary Salvage chemotherapy followed by HDT and rescue autologous stem cell transplant remains the standard of care for relapsed/refractory lymphoma. The role of novel agents to improve disease-related parameters remains to be elucidated in frontline induction, disease salvage, and high dose consolidation or in the maintenance setting.

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“…Attempts to improve on FFP in AHCT have included further intensification of salvage therapy before transplant [2-7], or intensification of the transplant conditioning regimen itself either with high dose sequential therapy [8-9] or with augmented carmustine (BCNU)-based regimens [10-16]. With increasing doses of BCNU from 300 mg/m 2 to 600 mg/m 2 , however, the incidence of pulmonary toxicity increases to 35% and higher [17-20]. When oral lomustine (CCNU) was substituted for BCNU in the conditioning, the interstitial pneumonitis incidence was as high as 63% [19].…”

Section: Introductionmentioning

confidence: 99%

Phase I/II Trial of GN-BVC, a Gemcitabine and Vinorelbine-Containing Conditioning Regimen for Autologous Hematopoietic Cell Transplantation in Recurrent and Refractory Hodgkin Lymphoma

Arai

Letsinger

Wong

et al. 2010

Biology of Blood and Marrow Transplantation

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Autologous hematopoietic cell transplantation with augmented BCNU-regimens is effective treatment for recurrent or refractory Hodgkin lymphoma (HL), however BCNU-related toxicity and disease recurrence remain challenges. We designed a conditioning regimen with gemcitabine in combination with vinorelbine in an effort to reduce the BCNU dose and toxicity without compromising efficacy. In this phase I/II dose escalation study, the gemcitabine maximum tolerated dose (MTD) was determined at 1250 mg/m2, and a total of 92 patients were treated at this dose to establish safety and efficacy. The primary endpoint was the incidence of BCNU-related toxicity. Secondary endpoints included 2-year freedom from progression (FFP), event-free survival (EFS), and overall survival (OS). Sixty-eight patients (74%) had one or more previously defined adverse risk factors for transplant (stage IV at relapse, B symptoms at relapse, greater than minimal disease pre-transplant). The incidence of BCNU-related toxicity was 15% (95% confidence interval, 9% to 24%). Only 2% of patients had a documented reduction in diffusing capacity of 20% or greater. With a median follow-up of 29 months, the FFP at 2 years was 71% and the OS at 2 years was 83%. Two-year FFP was 96%, 72%, 67%, and 14% for patients with 0 (n=24), 1 (n=37), 2 (n=23), or 3 (n=8) risk factors, respectively. Regression analysis identified PET status pre-transplant and B symptoms at relapse as significant prognostic factors for FFP. This new transplant regimen for HL resulted in decreased BCNU toxicity with encouraging FFP and OS. A prospective, risk-modeled comparison of this new combination with other conditioning regimens is warranted.

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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

Cited by 28 publications

References 46 publications

Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

A Review of Autologous Stem Cell Transplantation in Lymphoma

Phase I/II Trial of GN-BVC, a Gemcitabine and Vinorelbine-Containing Conditioning Regimen for Autologous Hematopoietic Cell Transplantation in Recurrent and Refractory Hodgkin Lymphoma

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