Transplantation For Hodgkin's Lymphoma Research Articles

Comparison of efficacy and toxicity according to etoposide and cytarabine dosing in BEAM conditioning followed by autologous stem cell transplantation in Hodgkin lymphoma

The combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem cell transplantation (ASCT) is a commonly used intensification regimen for patients with Hodgkin lymphoma. As etoposide and cytarabine dosing are not defined, we conducted a retrospective, multicenter study, to compare efficacy and toxicity in 130 patients with Hodgkin lymphoma receiving etoposide and cytarabine at either 200 mg/m2/d (n = 50), 400 mg/m2/d (n = 35), or etoposide 200 mg/m2/d and cytarabine 400 mg/m2/d (n = 45). Progression-free survival and overall survival were not associated with the intensity of conditioning. Increased conditioning intensity was associated with longer duration of thrombocytopenia, a higher number of transfused RBC and platelet units and a higher frequency of mucositis, but serious adverse events or infectious complications were not increased. The intensity of BEAM regimen was not associated with survival but with the rate of cytopenia and mucositis advocating for the use of lower dosing in frail patients.

The role of transplantation in Hodgkin lymphoma.

Despite the success of frontline anthracycline-based chemotherapy for classical Hodgkin Lymphoma (cHL), approximately 15% of patients do not achieve an adequate response and require further therapy. For transplant-eligible patients, additional treatment followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autoHCT) provides a durable response in 50% of patients. The most refractory patients, including those requiring multiple lines of therapy to achieve a response or those relapsing after an autoHCT, may achieve long-term survival with allogeneic hematopoietic stem cell transplant (alloHCT). Contemporary salvage regimens used as a bridge to transplant have expanded to include not only non-cross resistant chemotherapy, but also brentuximab vedotin (BV) and checkpoint inhibitors (CPI). As the management of relapsed/refractory (R/R) cHL evolves with the introduction of novel agents, so too does the role of transplantation. The paradigm of chemosensitivity as a predictor for autoHCT efficacy is being challenged by favorable post- autoHCT outcomes in heavily pre-treated CPI-exposed patients. Contemporary supportive care measures, validated comorbidity assessments, and an increased donor pool with haploidentical donors have broadened the application of transplantation to an increasingly older and diverse patient population. Despite the introduction of increasingly effective treatment options for R/R cHL, transplantation continues to play an important role in the management of these patients. In this review, we explore the impact of salvage therapy on autoHCT, conditioning regimens, maintenance therapy and the diminishing role of alloHCT for patients with cHL.

Allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma in Switzerland, 20 years of experience: 2001-2020.

Despite the high cure rate with initial therapy, approximately 10% of Hodgkin lymphoma (HL) patients are refractory to initial treatment, and up to 30% of patients will relapse after achieving initial complete remission. Despite promising initial results of treatment by immune checkpoint inhibitors, most patients will eventually progress. We analyzed 62 adult patients with relapsed or refractory HL (rrHL) treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in one of three University Hospitals of Switzerland (Zurich, Basel, and Geneva) between May 2001 and January 2020. The primary endpoint was overall survival (OS). Secondary endpoints were relapse-free survival (RFS), non-relapse mortality (NRM), and relapse incidence, which were assessed in univariate analysis. The median follow-up was 61 months (interquartile range 59-139). The 2- and 5-year OS was 54% (standard error (SE) ±12) and 50.2% (SE ±13.3), respectively, and the 2- and 5-year RFS was 40.7% (SE ±16.3) and 34.4% (SE ±19.0), respectively. NRM was 23.1% (SE ±2.2) and 27.4% (SE ±2.5) at 2 and 5 years, respectively. The cumulative incidence of relapse was 36.1% (SE ±5.6) at 2 years and 38.2% (SE ±6.6) at 5 years. Our analysis of allo-HSCT outcomes in the context of rrHL shows encouraging OS and RFS rates, with the mortality rate reaching plateau at 50% at 2 years after allo-HSCT. This confirms that allo-HSCT still remains as a potentially curative option for half of patients with rrHL.

Rituximab as adjunctive therapy to BEAM conditioning for autologous stem cell transplantation in Hodgkin lymphoma.

While high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) leads to improved disease-free survival (DFS) for children and adults with relapsed/refractory Hodgkin lymphoma (HL), relapse remains the most frequent cause of mortality post-transplant. Rituximab has been successfully incorporated into regimens for other B-cell lymphomas, yet there have been limited studies of rituximab in HL patients. We hypothesized that adding rituximab to BEAM (carmustine, etoposide, cytarabine, melphalan) conditioning would reduce relapse risk in HL patients post-transplant. Here, we retrospectively review the outcomes of patients with relapsed/refractory HL who received rituximab in addition to BEAM. The primary outcome was DFS. Our cohort included 96 patients with a median age of 28 years (range, 6-76). Majority of patients (57%) were diagnosed with advanced (Stage III-IV) disease, and 62% were PET negative pre-transplant. DFS was 91.5% at 1 year [95% CI 86-98%], and 78% at 3 years [95% CI 68-88%]. NRM was 0% and 3.5% at 1-year [95% CI 0-3%] and 3-years [95% CI 0-8.5%], respectively. 25% of patients developed delayed neutropenia, with 7% requiring infection-related hospitalizations, and one death. We have demonstrated excellent outcomes for patients receiving rituximab with BEAM conditioning for relapsed/refractory HL. Future comparative studies are needed to better determine whether rituximab augments outcomes post-transplant.

An Australasian Bone Marrow Transplant Registry (ABMTR) Study of the Trends and Outcomes of Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) in Hodgkin Lymphoma between 2009-2019: Relapse Remains the Most Common Cause of Death Post Transplantation

An Australasian Bone Marrow Transplant Registry (ABMTR) Study of the Trends and Outcomes of Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) in Hodgkin Lymphoma between 2009-2019: Relapse remains the most common cause of death post transplantation Introduction: Hodgkin Lymphoma (HL) is an eminently curable disease, with 80% of cases achieving cure with first line therapies. There are a subset of patients who relapse and require salvage therapy including autologous stem cell transplant and more recently novel agents such as brentuximab vedotin (BV) and the PD-1 inhibitors. The latter are less toxic and achieve durable responses but are not considered curative for most (LaCasce et al., 2019). In Australia BV and PD-1 inhibitors were approved in December 2013 and September 2017 respectively. Allogeneic HSCT offers a graft vs lymphoma (GVL) effect that may contribute to long term survival in some patients (Peggs et al., 2005). The introduction of reduced intensity conditioning (RIC) has seen improved outcomes with an OS of 67% (59-74%) and Progression Free Survival (PFS)of 45% (35-56%) (Rashidi et al., 2016) Patients and methods: Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients receiving a first allogeneic transplant for HL between 2009 and 2019. The Kaplan Meier method was used to calculate OS and PFS with log rank test for comparison. Multivariable Cox proportional hazards models were used to identify associations with OS. We divided the patients into 5 year cohorts to compare transplant outcomes over time. Results: A total of 149 patients from 16 sites in Australia and New Zealand were included. The median age at time of transplant was 31 years (range 19-61) and the majority were male (60%). Seventy-five percent of patients had undergone previous autologous HSCT with data missing for 22%. Median follow up was 75 months (range 4.7-137.1). Forty five percent of patients were in complete remission (CR), 34% in partial remission and 15% relapsed/primary refractory (RR) at the time of HSCT with information missing in 4%. The majority of donors were matched unrelated donors (47%) and sibling donors were used for 37% of patients, haploidentical in 11% and umbilical cord blood in 5%. Reduced intensity conditioning was used in 86% of patients and in vivo T cell depletion with ATG or alemtuzumab was used in 27%. Acute GVHD occurred in 53/149 (30%) of which 31% was grade III-IV. In patients who survived beyond 100 days, the incidence of chronic GVHD was 38%, of which 53% was preceded by some form of aGVHD. Non-relapse mortality (NRM) at 100 days was 8% with 5/12 of these patients dying from aGVHD. Two-year OS and PFS were 75% and 49% respectively. A period effect was not detected with no significant difference in OS (p=0.8) nor PFS (0.2) based on transplant year (figure 1a & 1b). Multivariate analysis of factors associated with OS identified age at transplant of >40 (HR 3.24, 95% CI 1.71-6.15, p<0.001) and RR disease at time of transplant (HR 3.07, 95% CI 1.44-6.54, p=0.004) with a higher risk of death. The numbers of HSCT performed each year are illustrated in figure 1c, with a larger proportion of patients in CR from 2014 onward. Post-transplant relapse occurred in 38% of patients (figure 1d)with a median time to relapse of 8.5 months (range 0.2 -42). Forty-eight percent (27/56) of patients who relapsed post HSCT were in CR at the time of HSCT. Of those who relapsed, 37% died due to progressive disease with no evidence of chronic GVHD. Relapse was the most common cause of death (37%) Conclusion: Although the rates of HSCT for HL in Australia and New Zealand have not varied over the past decade despite the availability of novel agents, there is a larger proportion of patients in CR prior to transplant. Survival outcomes for HL post HSCT are comparable to those reported internationally. Despite a higher percentage of patients transplanted in CR in later years, relapse post HSCT remains the major cause of death. Further studies to examine strategies to prevent or treat relapse of HL post-allograft are needed. Disclosures Sharplin: Novartis: Other: FUnded to attend Australian Haematology Conference . Di Ciaccio:Jansen: Honoraria, Other: travel and accomodation grant. Spencer:AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria; Celgene, Janssen and Takeda: Speakers Bureau. Greenwood:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hamad:Abbvie: Honoraria; Novartis: Honoraria.

A Comparison of the BEAM and MITO/MEL Conditioning Regimens for Autologous Hematopoietic Stem Cell Transplantation in Hodgkin Lymphoma: An Analysis of Efficiency and Treatment-Related Toxicity

BackgroundApproximately half of patients with relapsed chemosensitive disease achieve robust responses with BEAM (BCNU, etoposide, cytarabine, and melphalan) and autologous stem cell rescue. The scarcity of comparative studies further limits alternative treatment protocols, such as the MITO/MEL (mitoxantrone, melphalan) protocol. Patients and MethodsIn this retrospective multicenter study, we compared the BEAM and MITO/MEL regimens used before autologous hematopoietic stem cell transplantation (ASCT) in terms of efficacy and side effects in patients with Hodgkin lymphoma. Data met international accreditation rules. Before ASCT, 108 patients received the MITO/MEL, and 34 patients received the BEAM. ResultsThe median follow-up time was 36 months in the MITO/MEL group (range, 3-178) and 23 months in the BEAM group (range, 4-99). After ASCT, the 3-year expected overall survival and disease-free survival rates were 86.1% and 86.1% for the MITO/MEL group and 91.3% and 76.5% for the BEAM group, respectively. Although 50% of patients developed febrile neutropenia attacks in the MITO/MEL group, this rate was 91.1% in the BEAM group. The grade II and higher rates of hepatic, renal, gastrointestinal, and cardiac toxicities were similar in both groups. However, the rate of pulmonary toxicity was determined to be 1.9% in the MITO/MEL group and 29.4% in the BEAM group (P < .001). ConclusionThe MITO/MEL conditioning regimen seems to be as effective as the BEAM regimen but has better tolerability in terms of pulmonary toxicity and may be used as an alternative option if necessary, depending on the comorbidity status of the patient.

The role of transplantation in Hodgkin lymphoma

Autologous stem cell transplantation is the standard salvage strategy for young and fit patients with Hodgkin lymphoma failing induction therapy, and is effective in nearly 50% of cases. The quality of response at transplantation is the most relevant prognostic aspect, as patients in complete response can obtain better outcomes. Therefore, first-line salvage treatments applied before transplantation need to produce high quality responses without excessive myelotoxicity and without affecting peripheral blood stem cell mobilisation. In this sense, the incorporation of new agents active in Hodgkin lymphoma, such as brentuximab vedotin and anti-programmeddeath 1 antibodies, in conventional regimens, may help to enhance complete remission rates. Working on conditioning regimen and applying a post-autologous consolidation treatment (for example with brentuximab vedotin) are two ways for improving transplant outcomes, particularly in patients displaying high-risk features for early relapse or progression. Allogeneic transplantation maintains its curative potential also in the era of new drugs, although its most correct timing and the most suitable sequence of post-autologoussalvage treatments still remain to be determined.

Nivolumab salvage therapy before or after allogeneic stem cell transplantation in Hodgkin lymphoma.

Nivolumab salvage therapy before or after allogeneic stem cell transplantation in Hodgkin lymphoma

Allogeneic Stem Cell Transplantation in Hodgkin Lymphoma: The Timing of Relapse after Autologous Transplant and Primary Refractory Disease Do Not Impact the Survival Outcomes

The present study retrospectively analyzed a cohort of consecutive relapsed/refractory Hodgkin lymphoma (RR-HL) patients receiving allogeneic stem cell transplantation (alloSCT) in a single center with a thiotepa-based conditioning to understand whether the timing of relapse after autologous stem cell transplant (ASCT) or the primary refractory disease would change the survival.Of 247 patients with HL referred to our division from 2001 to 2014, 109 had RR-HL (64 primary refractory). After receiving salvage treatment, 62 patients (57%) underwent alloSCT with a thiotepa-based conditioning; 4 patients (4%) received fludarabine-melphalan conditioning in a phase II study, 43 patients (39%) did not receive alloSCT for progressive disease (31), advanced age (>65 years, 3 patients) or for achieving a complete response after a third-line chemotherapy consolidated by ASCT (9).This study analyzes the outcomes of the 62 consecutive patients allografted with thiotepa-based conditioning, which consisted of thiotepa, fludarabine, and cyclophosphamide (TFC) for patients with an HLA identical sibling donor, TFC plus anti-thymocyte globulin for matched unrelated (MUD) donors, TFC plus alemtuzumab and 2-Gray (Gy) total body irradiation (TBI) for T-deplete haploidentical alloSCT, or TFC plus 2-Gy TBI and post-transplant cyclophosphamide for T-replete haploidentical alloSCT. Multivariate analysis of alloSCT outcomes included as covariates the pre-transplant disease status (CR vs PR vs resistant), donor (HLA identical, MUD, or T-deplete or T-replete haploidentical), primary refractory disease (yes vs no) and timing of relapse after ASCT (<12 mos after ASCT vs >12 mos vs no ASCT).Patients had a median of 33 years at alloSCT, 76% of them had a primary refractory disease at diagnosis. 74% of patients relapsed <12 months after ASCT, 15% relapsed >12 months after ASCT, 11% underwent alloSCT without previous ASCT. At alloSCT, 25% had resistant disease whereas 75% were in partial (31%) or complete response (44%) after the last salvage treatment. Donors were HLA identical siblings (42%), MUD (29%), or haploidentical (21% T-deplete, 8% T-replete).Median follow-up was 5.4 years. Three- and 5-years OS was 61 and 59%, PFS and relapse incidence were 46% and 38% at both 3 and 5 years. Non-relapse mortality (NRM) was 10% at 100 days, 17% at 1 year and for the entire follow-up. In multivariate analysis, the timing of relapse after ASCT and primary refractory disease did not impact the transplant outcomes. OS was reduced by resistant disease at alloSCT (HR=4.01, CI95% 1.34-11.97, p=0.012) and by T-depleted haploidentical transplant (HR=3.81, CI 95% 1.36-10.66, p=0.010). PFS and relapse incidence were impacted only by resistant disease (HR=5.54, CI 95% 2.13-14.37, p<0.001, and HR=6.75, CI 95% 2.07-21.96, p=0.001, respectively). NRM was significantly impacted only by the use of T-depleted haploidentical grafts (HR=7.63, CI95% 1.07-54.31, p=0.042).In conclusion, the pre-transplant disease status and not the timing of relapse after ASCT or primary refractory disease, impacts OS, PFS and relapse of RR-HL patients allografted with thiotepa-based conditioning. An optimal response before alloSCT is critical to maximize the long-term benefit of alloSCT. In the era of novel agents this can be a realistic goal for the majority of patients. DisclosuresViviani:Takeda Italia SpA: Consultancy; Teva Italia SpA: Consultancy; Italfarmaco SpA: Consultancy; Takeda International: Consultancy.

Outcomes of Salvage Stem Cell Transplantation in Hodgkin Lymphoma in a Single Institution in the Modern Era

Background: Though overall Hodgkin lymphoma (HL) carries one of the best outcomes among lymphoma, about 40% of patients relapse and/or fail to respond to initial therapy. Out of those about half can be cured with salvage therapy followed by high dose therapy and autologous stem cell transplantation (ASCT) while eligible patients who fail and/or relapse after HDT-ASCT are offered nonmyeloablative stem cell transplantation. Achieving a negative PET response prior to ASCT correlate with superior outcome in HL regardless of their clinical presentation. More recently novel therapies have emerged in the field from brentuximab vedotin approved in r/r setting in HL as well as checkpoint inhibitors currently in trials with very promising results. This study analyzed a cohort of HL pts transplanted at our institution over the last 5 years to identify potential new patterns in the evolving landscape of HL.Methods: We performed a retrospective analysis of r/r HL pts referred to our center for salvage therapy at our institution between 2009 and 2014 using the Blood and Bone marrow transplant database at HUMC.Results: A total of 66 patients with r/r HL transplanted at HUMC were identified. Baseline characteristics were as follows: male 57%, female 43%, median age 36.8y (range 16-66), Frontline therapy was ABVD in all but one pt who received Gemzar, Vinorelbine, Doxil; and 27% pts received consolidation w/ radiation. Median time to relapse was 7mo (range 0.93-87mo), stage at first relapse I-0, II-33%, III-20%, IV-23%, NA 24%. The salvage regimen used was ICE in 54 pts, brentuximab vedotin in 8 pts and HCVAD in 4 pts. Involved field radiation was used in 10% at salvage prior to HDT-ASCT. Responses after first salvage were as follows: PET-CR 59%, CT-CR 5%, PR-14%, PD-12%, NA-10%. As per our practice, pts not in CR after first salvage continue to the next salvage until they reach a CR. Pts not in CR after 2 lines of salvage were considered for allogeneic stem transplantation (alloSCT). Conditioning regimen was BEAM prior to ASCT, reduced intensity (fludarabine-based) prior to alloSCT. Source of allo stem cells was: MRD in 7 pts, MUD in 3 pts, haploidentical donor in 2 pts. A total of 59 pts had ASCT, 6 pts had alloSCT as first transplant (primary refractory), while 6 pts underwent alloSCT for relapse after ASCT. Disease status post first transplant was as follows: PET-CR 76%, CT-CR 17%, PR-1%, PD-6%. All 6 alloSCT pts are alive in remission, while 13 out of 59 ASCT pts have relapsed, 7 relapses occurred within the first year, 3 within the second year post ASCT. Out of 6pts with alloSCT after ASCT relapse, 4 pts are alive in CR, one died from PD, one died from PTLD (in CR from HL). After a median follow up of 24.5 mo (3.7-70), the 3y PFS and OS are 73% and 95% respectively. For CR and PR after first salvage to SCT pts, median PFS and OS has not been reached. For SD/PD after first salvage therapy pts median PFS is 14.5mo, median OS 47mo. No significant difference in mPFS and mOS is seen in pts who received one vs more than one salvage therapy prior to ASCT or had radiation as part of frontline or salvage therapy.Conclusion: We report on a consecutive series of high-risk r/rHL. Our results demonstrate an improved outcome compared to historical data. Pts requiring more than one salvage prior to SCT while having mPFS of only 14.5 mo, have prolonged survival at median 47 mo.While the number is small, selected young pts with high risk relapsed HL may benefit from alloSCT. Strategy of requiring CR prior to SCT, and alloSCT (instead of ASCT) in pts requiring more than 2 consecutive salvage regimens, availability of novel agents, diminishing use of RT may have contributed to observed improved outcomes. DisclosuresFeldman:Pharmacyclics/JNJ: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau. Vesole:Idera Pharmaceuticals: Research Funding; Celgene Corporation: Speakers Bureau. Skarbnik:Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau. Goy:Acerta: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/JNJ: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Second cancer risk in adults receiving autologous haematopoietic SCT for cancer: a population-based cohort study

Population-based evidence on second cancer risk following autologous haematopoietic SCT (HCT) is lacking. We quantified second cancer risk for a national, population-based cohort of adult Australians receiving autologous HCT for cancer and notified to the Australasian Bone Marrow Transplant Recipient Registry 1992-2007 (n=7765). Cancer diagnoses and deaths were ascertained by linkage with the Australian Cancer Database and National Death Index. Standardized incidence ratios (SIRs) were calculated and Cox regression models were used to estimate within-cohort risk factors treating death as a competing risk. During a median 2.5 years follow-up, second cancer risk was modestly increased compared with the general population (SIR 1.4, 95% confidence interval 1.2-1.6); significantly elevated risk was also observed for AML/myelodysplastic syndrome (SIR=20.6), melanoma (SIR=2.6) and non-Hodgkin lymphoma (SIR=3.3). Recipients at elevated risk of any second cancer included males, and those transplanted at a younger age, in an earlier HCT era, or for lymphoma or testicular cancer. Male sex, older age (>45 years) and history of relapse after HCT predicted melanoma risk. Transplantation for Hodgkin lymphoma and older age were associated with lung cancer risk. Second malignancies are an important late effect and these results inform and emphasize the need for cancer surveillance in autologous HCT survivors.

Allogeneic Stem-Cell Transplantation in Hodgkin Lymphoma; A More Favorable Outcome in Patients With Chemo-Sensitive Disease and With Treosulfan-Based Conditioning

s / Biol Blood Marrow Transplant 19 (2013) S233eS256 S239 constructed in our unit consisting of intravenous Busulphan (Busilvex) (3.2mg/kg/day for 3 days), Etoposide (400mg/m2/ day for 2 days) and Melphalan (140mg/m2) (BEM). We retrospectively analysed the outcome of patients (pts) who underwent AHCT following conditioning with the standard BEAM and BEM regimen. The pts were stratified by age, pretransplantation disease phase and previous lines of treatment. In total, 50 pts conditioned with BEM (group A) and 93 pts with BEAM (group B) were included. Group B pts were selected among 184 pts who underwent AHCT with BEAM regimen during the last decade. Stratification by disease risk was followed by a 1:2 selection. Fifty percent of the pts were younger than 34 in both study groups with a range of 11-68 years old. The pts of group B were more likely to suffer from HL (63) than NHL (30); whereas disease diagnosis for group A was HL in 28 and NHL in 22 pts. Disease was chemoresistant to salvage treatment in 46% of group A pts versus (vs) 23% of group B pts. There were no other significant differences concerning the patients’ characteristics such as age above median, pre-transplantation lines of treatment (1-2: 40%, 34: 46%, 5: 14%), disease status (complete remission: 27%, primary refractory: 52%, relapse: 21%), advanced stage disease (52%). Complete remission post-AHCT was obtained in 50% of group A and 56% of group B pts. Progression free survival (PFS) at 2 years and overall survival (OS) were similar among the two study group populations (66% vs 63% and 80% vs 78% respectively). Given the fact that there were more pts with chemoresistant disease in group A, a second matched pair analysis was conducted upon stratification by disease chemosensitivity to salvage treatment instead of age as a risk factor. Efficacy was again similar for both conditioning regimens. In multivariate analysis favorable factors in terms of PFS were HL, chemosensitivity to salvage treatment and stage <IIB whereas in terms of OS non-bulky disease, HL and stage <IIB. Treatment related mortality (TRM) was 3.2% (3/93 pts) in group B and no TRM in group A. Detailed toxicity associated with the two study regimens is further analyzed. There are currently no randomized studies clarifying the optimal conditioning among multiple regimens in terms of efficacy and toxicity. In this study the two conditioning regimens, BEAM and BEM, were found to be equivalent. Additionally, the efficacy of the newly designed BEM regimen in chemoresistant and advanced stage disease is encouraging.

The Role of Autologous Transplantation in Hodgkin Lymphoma

Between 80% and 90% of Hodgkin lymphoma (HL) patients can be cured with up-to-date combined-modality treatments, but patients with disease refractory to first-line therapy and those who relapse after first-line therapy still have a relatively poor prognosis. Dose intensification with stem cell support has been evaluated both to avoid relapses and to cure patients with refractory or relapsed disease. In this review, we focus on the use of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in first-line, second-line, and third-line therapy for HL patients. The relevance of salvage therapy before high-dose chemotherapy is discussed, as well as the role of sequential high dose chemotherapy. We also review current evidence for tandem transplantation in high-risk HL patients and ASCT in elderly patients. Finally, we discuss current concepts of ASCT for HL patients and the use of functional imaging and consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Does It Have a Place in Treating Hodgkin Lymphoma?

Although the majority of patients with Hodgkin lymphoma achieve sustained remission with frontline treatment, there is still a subset of patients with much less favorable prognosis. The current standard of care for Hodgkin lymphoma patients with relapsed or refractory disease is autologous stem cell transplantation. However, no randomized trial has compared autologous stem cell transplantation with allogeneic stem cell transplantation prospectively, and most studies comparing allogeneic stem cell transplantation with historical controls of autologous stem cell transplantation use a myeloablative conditioning reference group. With the more frequent use of reduced-intensity conditioning transplantation in recent studies, the role for allogeneic stem cell transplantation in Hodgkin lymphoma patients is being redefined. In contrast to other types of lymphomas, Hodgkin lymphoma patients are younger at diagnosis, which makes a curative strategy such as allogeneic stem cell transplantation particularly appealing. This review examines the role of allogeneic stem cell transplantation in Hodgkin lymphoma by looking at both retrospective and prospective analyses in the era of reduced-intensity conditioning transplantation, donor lymphocyte infusions, and biologically based treatments.

Does location matter? Rural vs urban outcomes after blood and marrow transplantation in a population-based Canadian cohort

Specialized health services, such as blood and marrow transplantation (BMT), are usually based in large urban centers. Previous research has suggested that rural patients undergoing BMT have a higher risk of death. We performed a cohort study using data from both the Manitoba BMT Program and the provincial Cancer Registry to determine whether patients from the rural areas would have inferior survival after BMT and whether rural patients have reduced access to BMT. A total of 463 adult Manitobans, who underwent BMT between January 1990 and December 2006, were assessed. We analyzed area of residence (rural vs urban), disease and BMT characteristics, and calculated the OS. Patients undergoing autologous and allogeneic transplants were analyzed separately. When adjusted for gender, age at BMT and year of BMT, area of residence was not a significant predictor of mortality. A relative survival analysis was also conducted, and area of residence was again not a significant predictor of mortality. To measure access to BMT in urban vs rural patients, we evaluated all patients with newly diagnosed Hodgkin's Lymphoma (HL) during this same period. Of 432 Manitobans diagnosed with HL, 182 (42%) were rural and 250 (58%) were urban. In contrast, 69% of patients undergoing transplant for HL were urban. In conclusion, using population-based data from a Canadian province, we were unable to show a survival disadvantage for rural patients after controlling for other variables. BMT utilization in rural populations deserves further study.

Results of autologous transplants for lymphomas from a tertiary cancer center in India

7106 Background: Autologous stem cell transplanation is the standard of care for patients of relapsed and refractory non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). We report the results of transplants in lymphomas from our center and role of possible prognostic factors. Methods: All 50 consecutive patients who underwent transplant for HL (70%) and NHL (30%) from August 1994- August 2008 were included in this retrospective study. Fifty eight percent of patients received BEAM (carmustine, etoposide, ara-c and melphalan), 30% LACE (lomustine, ara-c, cyclophosphamide and etoposide), 8% ICE (ifosfamide,carboplatin and etoposide) and 4% high dose melphalan (200mg/m2) conditioning regimens. Seventy eight percent of patients received peripheral blood stem cells (PBSC), 8% bone marrow (BM) and 14% both PBSC and BM. Prognostic factors evaluated for progression free survival (PFS) were serum albumin level and body mass index (BMI) at the time of transplant, stage at diagnosis and source of stem cells, while for over all survival (OS), status of disease at transplant was also included. Results: The median time to transplant was 2.25 years from the time of diagnosis. The median age at transplant was 25 years. Seventy four percent of patients were male. At the time of transplant, thirty two percent were in complete remission (CR), 50% in partial remission (PR) and 18% had refractory disease (RD). The median serum albumin and BMI at the time of transplant were 4 g/dl and 22.5 kg/m2 respectively. The best disease response rate was 86% (CR+PR) in patients evaluable for response. Thirteen patients relapsed at a median interval of 11 months post transplant. The cumulative probability of OS and progression free survival PFS at 5 years were 40% and 34% respectively for the whole group. Multivariate analysis using cox regression identified serum albumin greater than 4 g/dl and those receiving PBSC grafts as independently associated with improved OS and PFS. Conclusions: These data provide the first published report of outcomes of autologous transplants in lymphomas from India. Our data suggests that serum albumin level at the time of transplant and stem cell source are important prognostic factors for PFS and OS. No significant financial relationships to disclose.

Does Location Matter? a Population-Based Analysis of Survival after Blood and Marrow Transplantation in Rural Versus Urban Manitobans

Objective: Specialized health services such as blood and marrow transplantation (BMT) are based in large urban centres. A previous study suggested that rural patients may have inferior outcomes after BMT. We hypothesized that rural Manitobans have reduced access to BMT and higher mortality rates after BMT than urban Manitobans.Methods: This population-based historical cohort study was based in Manitoba, Canada, a province of 1.2 million people that is served by a single, publicly funded BMT program. We utilized data from both the Manitoba BMT Program and the provincial Cancer Registry. Consecutive adult Manitobans who underwent BMT at Health Sciences Centre, Winnipeg between 01/1990 and 12/2006 were assessed. We analyzed distance of residence from the BMT centre, disease and BMT characteristics, and calculated overall survival (OS). Secondly, to measure access to BMT, we evaluated all patients with newly diagnosed Hodgkin Lymphoma (HL) during this same period. We compared the proportion of rural and urban Manitobans diagnosed with HL to those who received a BMT for HL.Results: 464 Manitobans underwent BMT (179 rural, 285 urban). Rural Manitobans had inferior 5 year OS (45% vs. 37%, p<0.05). A gradient was apparent; patients who lived < 20 km from the BMT centre had superior 5 year OS, while those furthest away (>200km) had the poorest OS (p<0.05). In a univariate Cox regression model, rural patients had a mortality ratio of 1.18 (p <0.05), and those living 200km or more from Winnipeg had a mortality ratio of 1.40 (p = NS). When adjusted for gender, age at BMT, year of BMT, and graft type, distance from HSC was not a significant predictor of mortality. Only period of BMT and graft type were significant predictors. A relative survival analysis was also conducted. This model included only those variables available in population data (age at BMT, gender, distance from Winnipeg, year of BMT). In univariate analysis, rural patients had an excess mortality ratio of 1.35 (p <0.05), and those living more than 200 km from Winnipeg had had an excess mortality ratio of 1.52 (p = NS). However, in the adjusted relative survival analysis, distance from Winnipeg was not a significant predictor. Again, period of BMT was a significant predictor. 432 Manitobans were diagnosed with HL. 182 (42%) were rural, and 250 (58%) were urban. This was similar to 2006 Canadian census data for Manitoba, (54% urban). In contrast, 69% of patients undergoing transplant for HL were urban.Conclusions: Previous research has suggested that rural patients undergoing BMT have a higher risk of death. Using population-based data from a Canadian province, we were unable to demonstrate this finding. Both the Cox regression model and the relative survival analysis demonstrated non-significant associations between location and mortality after controlling for other variables. This may be due to relatively small number of patients residing 200 or more km from Winnipeg in our study. However, the non-significant relationship may also be due to more comprehensive long-term follow-up of patients within the BMT program. Lastly, there may be under-utilization of BMT in rural populations; this is an area that deserves further study.

Stem cell transplantation in Hodgkin lymphoma

Hematopoietic stem cell transplantation is an effective treatment for patients with relapsed or refractory Hodgkin lymphoma. Treatment outcome is better among patients who demonstrate sensitivity to salvage chemotherapy. Approximately half of the patients undergoing autologous stem cell transplantation will be cured and sequential high-dose therapy has been proposed as a means of improving these results further. Lifelong medical surveillance is required following transplantation to monitor for late toxicity, including second malignancy. For young patients who relapse following transplantation, reduced-intensity allogeneic transplantation has shown encouraging response rates, while second autologous stem cell transplantation, radiotherapy and palliative single-agent chemotherapy are other options. For patients with multiple relapses and chemotherapy refractory disease, novel approaches are necessary.