The Cell and Gene Therapy Consortium's Perspective on Harmonizing Data Collection for Patient Enrollment, Therapy Ordering and Scheduling, and Cell Collection.

Established in October 2021, the Cell and Gene Therapy (CGT) Consortium convened with the goal to bring together key CGT stakeholders - manufacturers, treatment centers, regulators, services providers, and ecosystem partners - to gain alignment on process definitions, terminology, challenges, and opportunities for process and data standardization from CGT program start-up and patient enrollment to therapy administration. With the recognition that the number of investigational and commercial cell and gene therapies will scale over the next several years, so will the number of manufacturer-specific processes and solutions (e.g., portals). As a result, this will increase the burden on academic medical centers, community hospitals, standalone clinics, collection facilities, and labs. Healthcare professionals (HCPs) and other industry stakeholders agree that a multiplicity of manufacturer portals with varying data requirements and nomenclature is unsustainable and adds unnecessary complexity - risk, cost, and time - in coordinating patient treatment. Following extensive discussions and multiple stakeholder meetings and interviews, we have developed a manuscript reporting on our activities and conclusions. Through the course of the manuscript, we delineate a framework for defining common principles, terminology, and user experiences for enrolling patients, ordering therapies, and collecting starting material in a standardized way. We also provide substantial background information on opportunities to streamline communications between manufacturing and healthcare organizations from the HCP end-user's perspective.

Are We Making PROGRESS in Preventing Graft-versus-Host Disease and Improving Clinical Outcomes? Impact of BMT CTN 1301 Study Results on Clinical Practice.

The need for prospective randomized clinical trials investigating novel graft-versus-host disease (GVHD) prevention strategies that include other clinical outcomes impacted by GVHD has been highlighted as a priority for the field of hematopoietic cell transplantation. A recently completed study through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1301) comparing CD34+ selection and post-transplantation cyclophosphamide with tacrolimus/methotrexate (Tac/MTX) for GVHD prevention demonstrated no significant differences in the primary endpoint of chronic GVHD relapse-free survival among the 3 approaches. The trial did not demonstrate a superior approach compared with Tac/MTX; however, it did highlight several challenges in determining the best and most relevant approaches to clinical trial design, particularly in the context of current and ongoing changes in real-world practices. Here we review the results of BMT CTN 1301 and their implications for clinical practice and future clinical trial design.

Socioeconomic and Racial Disparity in Chimeric Antigen Receptor T Cell Therapy Access.

Chimeric antigen receptor (CAR) T cell therapy is changing the paradigm in hematologic malignancies, but disparities in access exist in the real-world setting. Efforts to address and eliminate these disparities will ensure availability of this life-saving therapy. This study aimed to determine patterns of racial/ethnic distribution, socioeconomic strata, insurance coverage, and travel time of CAR T cell recipients. We used the Vizient Clinical Database (CDB) to capture and analyze elective encounters for CAR T administration as well as encounters for any reason other than CAR T administration (non-CAR T) in patients with lymphoma, myeloma, and acute lymphoblastic leukemia. Travel time and median household income were calculated based on ZIP code of residence. We found that African Americans (AA) were less likely than other racial/ethnic groups to receive CAR T cell therapy. In addition, AA and Hispanic participants were underrepresented in clinical trials. Among the patients with myeloma, all of whom received CAR T cell therapy on a clinical trial, only 1% were African American and 5.4% were Hispanic, and only 7.3% of CAR T cell therapy-related admissions were of patients from neighborhoods with a mean income <$40,000. Almost one-third of the CAR T cell recipients lived >2 hours away from the center in which they were treated; the majority of these patients were from the higher socioeconomic stratum (P < .001). There were fewer patients with Medicare and uninsured patients in the CAR T cell group. Our data indicate that socioeconomic stratum and insurance coverage are important underlying determinants of the identified disparities. Low clinical trial enrollment of minorities also feeds the inequity. Strategies to improve access need to be framed around addressing the causes for the observed disparities.

Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients.

Coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic in March 2020, and has caused more than 600,000 deaths in the United States at the time of this report. Hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor T cell (CAR-T) therapy recipients have a higher risk of mortality with COVID-19 owing to profound immune dysregulation. In this study, we investigated the impact of SARS-CoV-2 in HCT/CAR-T therapy recipients. This single-center prospective study included all (n = 58) adult HCT/CAR-T recipients who were diagnosed with COVID-19 at the University of Kansas Medical Center between March 2020 and May 2021. Baseline and disease-related characteristics were ascertained from medical records. Data were analyzed using SPSS version 21 (IBM, Armonk, NY). Bivariate analyses, using the chi-square and t-test, and logistic regression analyses were conducted. The study included 58 HCT/CAR-T patients who acquired SARS-CoV-2 infection, including recipients of allogeneic HCT (n = 32), autologous HCT (n = 23), and CAR-T therapy (n = 3). The median patient age was 58 years (range, 24 to 77 years), and 64% were males. The median time from HCT/CAR-T therapy to SARS-CoV-2 infection was 17.7 months (range, 0.2 to 201.9 months), and 22% of the patients acquired SARS-CoV-2 within the first 100 days post-HCT/CAR-T therapy. The primary hematologic disorders were plasma cell (36%), myeloid (38%), and lymphoid (26%) malignancies. Myeloablative conditioning was performed in 62% of patients. Donors were autologous (45%), matched sibling (15%), matched unrelated (21%), and haploidentical (19%). Prior history of grade II-IV acute graft-versus-host disease (GVHD), active GVHD, and current immunosuppressive therapy (IST) was noted in 22%, 31%, and 36% of patients, respectively. Concurrent infections were observed in 19%. Lymphopenia (P = .049) and high serum ferritin concentration (P = .020) were associated with mortality. COVID-19 severity was mild in 50% of the patients, moderate in 22%, and severe in 28%. Clinical findings included pneumonia or abnormal chest imaging (in 50%), hypoxia (28%), intensive care unit admission (19%), and mechanical ventilation (10%). Therapies included remdesivir (in 41%), convalescent plasma (35%), dexamethasone (22%), monoclonal antibodies (19%), and tocilizumab (3%). The median duration of viral shedding (positive SARS-CoV-2 PCR) was 7.7 weeks (range, 2 to 18.7 weeks), and 2 patients had a persistent infection for >5 months post-CAR-T therapy. After a median follow-up of 6.1 months (range, 0.5-13.6 months), the mortality rate was 16% in all patients and 28% in allogeneic HCT recipients. Among 9 patients who died, the median survival after SARS-CoV-2 infection was 23 days (range, 14 to 140 days). In survivors with moderate-severe COVID-19, the median time to recovery was 4.2 weeks (range, 1.1 to 24.7 weeks). Among allogeneic HCT recipients, 5 (16%) developed subsequent pulmonary chronic GVHD necessitating systemic steroids and additional IST. Significant predictors of COVID-19 severity included allogeneic HCT (odds ratio [OR], 3.6, 95% confidence interval [CI], 1.2 to 10.8; P = .020), history of grade II-IV acute GVHD (OR, 4.6; 95% CI, 1.10 to 18.86; P = .036) and concurrent IST (OR, 5.9; 95% CI, 1.8 to 19.8; P = .004). HCT and CAR-T cell therapy recipients are at an increased risk of moderate-severe COVID-19 pneumonia and higher mortality with SARS-CoV-2 infection. Our findings confirm the need for continuing vigilance with social distancing and masks, vaccination prioritization, close monitoring, and aggressive treatment of HCT/CAR-T therapy recipients.

Economic and Clinical Burden of Virus-Associated Hemorrhagic Cystitis in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation in the United States.

Hemorrhagic cystitis (HC) caused by viral infections such as BK virus, cytomegalovirus, and/or adenovirus after allogeneic hematopoietic stem cell transplantation (allo-HCT) causes morbidity and mortality, affects quality of life, and poses a substantial burden to the health care system. At present, HC management is purely supportive, as there are no approved or recommended antivirals for virus-associated HC. The objective of this retrospective observational study was to compare the economic burden, health resource utilization (HRU), and clinical outcomes among allo-HCT recipients with virus-associated HC to those without virus-associated HC using a large US claims database. Claims data obtained from the Decision Resources Group Real-World Evidence Data Repository were used to identify patients with first (index) allo-HCT procedure from January 1, 2012, through December 31, 2017. Outcomes were examined 1 year after allo-HCT and included total health care reimbursements, HRU, and clinical outcomes for allo-HCT patients with virus-associated HC versus those without. Further, a generalized linear model was used to determine adjusted reimbursements stratified by the presence or absence of any acute or chronic graft-versus-host disease (GVHD) after adjusting for age, health plan, underlying disease, stem cell source, number of comorbidities, baseline reimbursements, and follow-up time. Of 13,363 allo-HCT recipients, 759 (5.7%) patients met the prespecified criteria for virus-associated HC. Total unadjusted mean reimbursement was $632,870 for patients with virus-associated HC and $340,469 for patients without virus-associated HC. In a multivariable model, after adjusting for confounders, the adjusted reimbursements were significantly higher for virus-associated HC patients with and without GVHD compared to patients without virus-associated HC (P < .0001). Patients with virus-associated HC stayed 7.9 additional days in the hospital (P < .0001) and 6.1 additional days (P = .0009) in the intensive care unit (ICU) for the index hospitalization, as compared to patients without virus-associated HC. The hospital readmission rate was higher for allo-HCT patients with versus without virus-associated HC (P < .0001), resulting in 12.9 more days in the hospital (P < .0001) and 7.3 more days in the ICU (P < .0001) after the index hospitalization. Among patients with GVHD, those with virus-associated HC had significantly higher all-cause mortality as compared to those without virus-associated HC (23.2% versus 18.4%; P = .0035). In an adjusted analysis, patients with virus-associated HC had a significantly higher risk of mortality, regardless of the presence of GVHD. When stratified by GVHD, there were no significant differences in the baseline risk for renal impairment; virus-associated HC was associated with increased risk for renal impairment in the follow-up period in patients with or without GVHD (P < .0001 for both). After allo-HCT, patients with virus-associated HC have significantly higher health care reimbursements and HRU, with worse clinical outcomes, including renal impairment, irrespective of the presence of GVHD and significantly higher all-cause mortality in the presence of GVHD. Our results highlight the unmet clinical need for effective strategies to prevent and treat virus-associated HC in HCT recipients that may also reduce costs among these patients.

Acute myeloid leukemia or myelodysplastic syndrome with chromosome 17 abnormalities and long-term outcomes with or without hematopoietic stem cell transplantation.

INTRODUCTION: Chromosome 17 abnormalities, especially disorders of the 17p region and including TP53 gene mutations, result in very low rates of cure for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) treated with conventional chemotherapy or allogeneic hematopoietic cell transplant (allo-HCT). Our retrospective study analyzed outcomes in patients with chromosome 17 (ch17) abnormalities who received conventional chemotherapy followed by allo-HCT versus those who did not receive a transplant. We analyzed whether poor outcomes extend to patients with all types of ch17 abnormalities and the impact of concomitant TP53 gene mutations assessed by next-generation sequencing (NGS) on prognosis. METHODS: We retrospectively analyzed diagnostic and outcome data on 98 patients treated at our institution from 2012 to 2018 with AML or MDS who possessed ch17 abnormalities by cytogenetic analysis. The presence of TP53 mutations was analyzed by NGS. Primary endpoint of our study was overall survival (OS). RESULTS: 61 patients with AML and 37 with MDS were included. Complete remission (CR) with first line treatment was similar between induction chemotherapy or hypomethylating agents (HMA), 22.9 % versus 21.6 % (p = 0.33). Median OS for all patients (with or without transplant) was 10 months. Patients with abnormal ch17 in conjunction with any TP53 mutation(s) exhibited worse OS compared to patients without a TP53 mutation (10 versus 23 months, p = 0.02). 30 patients (19 AML, 11 MDS) underwent HCT, with a median OS of 11 months. For AML patients who underwent allo-HCT, 18 were in CR (13 with cytogenetic remission) and 1 had persistent disease at transplant. In the MDS cohort, 3 patients were in CR (2 with cytogenetic remission) and 8 had stable disease. Post allo-HCT survival of AML and MDS cohorts did not differ (p = 0.6), although cytogenetic CR at time of HCT trended towards improved OS (17 versus 8 months; p = 0.6). CONCLUSIONS: AML/MDS patients with ch17 abnormalities have poor outcomes with or without HCT. Our results show that patients with ch17 abnormalities and TP53 mutations have a significantly poorer survival compared to patients who have ch17 abnormalities but no TP53 mutations. Drugs targeting abnormalities of the p53 pathway, improvement in depth of response prior to HCT, and novel maintenance strategies are needed for improved outcomes in these patients.

Health Care Reimbursement, Service Utilization, and Outcomes among Medicare Beneficiaries with Multiple Myeloma Receiving Autologous Hematopoietic Cell Transplantation in Inpatient and Outpatient Settings.

Autologous hematopoietic stem cell transplantation (auto-HCT) is a complex procedure that can be performed in both inpatient (IP) and outpatient (OP) care settings. We examined reimbursement, service utilization, and patient financial responsibility among Medicare beneficiaries with multiple myeloma who underwent auto-HCT in the IP and OP settings using a merged dataset of the Center for International Blood and Marrow Transplant Research observational database and Centers for Medicare & Medicaid Services Medicare administrative claims data. Selection criteria included first auto-HCT, time from diagnosis to auto-HCT <18 months, and continuous enrollment in Medicare Parts A and B for 30 days before HCT index claims and 100 days post-HCT or until death. Total reimbursement and patient responsibility were adjusted for patient and disease characteristics using a weighted generalized linear model. The final cohort comprised 1640 patients, 1445 (88%) who received IP-HCT and 195 (12%) who received OP-HCT. The adjusted total mean reimbursement was higher for IP-HCT compared with OP-HCT ($82,368 [95% CI, $77,643 to $87,381] versus $46,824 [95% CI, $43,567-$50,325]; P < .0001). Adjusted total mean patient responsibility was $4736 for IP-HCT (95% CI, $4731 to $5133) and $6944 for OP-HCT (95% CI, $6296 to $7658) (P < .0001). Within 100 days post-HCT, 107 of the 195 OP-HCT recipients (55%) had at least 1 subsequent admission, compared with 348 of the 1445 IP-HCT recipients (24%). Reimbursement, service utilization, and financial responsibility varied by HCT setting. As the number of Medicare beneficiaries who undergo auto-HCT increases, coverage policy needs to consider how location of services leads to variations in the financial burden for both hospital systems and patients.

Results of the First Clinical Study in Humans That Combines Hyperbaric Oxygen Pretreatment with Autologous Peripheral Blood Stem Cell Transplantation.

Patients undergoing high-dose chemotherapy and autologous hematopoietic cell transplantation (auto-HCT) are at risk for multiple morbidities, including mucosal inflammation and neutropenic fever, both related to neutropenia. Evidence from our preclinical work in an umbilical cord blood (UCB) transplantation murine model suggests that treatment with hyperbaric oxygen (HBO) before UCB infusion improves UCB CD34+ cell engraftment by reducing erythropoietin levels. A pilot clinical trial using HBO in patients undergoing UCB transplantation showed improvement in kinetics of blood count recovery. In this study, we evaluated HBO in combination with auto-HCT. Our primary aim was to determine the safety of HBO in this setting and secondarily to determine its efficacy in reducing time to neutrophil and platelet engraftment compared with matched historic controls. Patients with multiple myeloma, non-Hodgkin lymphoma, and Hodgkin disease eligible for auto-HCT were included. On day 0, patients received HBO treatment consisting of exposure to 2.5 atmosphere absolutes for a total of 90 minutes, in a monoplace hyperbaric chamber, breathing 100% oxygen. Six hours after the start of HBO, peripherally mobilized stem/progenitor cells were infused and patients were followed daily for toxicity and blood count recovery. All patients received daily granulocyte colony-stimulating factor starting on day +5 and until absolute neutrophil count (ANC) of ≥1500 or ANC of 500 for 3 consecutive days. A matched historic cohort of 225 patients who received auto-HCT between January 2008 and December 2012 was chosen for comparison and matched on sex, age, conditioning regimen, and disease type. We screened 26 patients for this study; 20 were treated and included in the primary analysis, and 19 completed the HBO therapy and were included in the secondary analysis. Although the median time to neutrophil count recovery was 11 days in both the HBO and control cohorts, the Kaplan-Meier estimates of the full distributions indicate that the time to neutrophil recovery was generally about 1 day sooner for HBO versus historical controls (log-rank P = .005; range, 9 to 13 for HBO patients and 7 to 18 for controls). The median time to platelet count recovery was 16 days (range, 14 to 21) for HBO versus 18 days (range, 11 to 86) for controls (log-rank P < .0001). In the secondary analysis comparing the HBO cohort who completed HBO therapy (n = 19) with our historical cohort, we evaluated neutropenic fever, growth factor use, mucositis, day +100 disease responses, and blood product use. HBO was associated with less growth factor use (median 6 days in HBO cohort versus median 8 days in controls, P < .0001). Packed RBC and platelet transfusion requirements were not statistically different between the 2 cohorts. Mucositis incidence was significantly lower in the HBO cohort (26.3% in HBO cohort versus 64.2% in controls, P = .002). HBO therapy appears to be well tolerated in the setting of high-dose therapy and auto-HCT. Prospective studies are needed to confirm potential benefits of HBO with respect to earlier blood count recovery, reduced mucositis, and growth factor use, and a cost-benefit analysis is warranted. © 2019 American Society for Blood and Marrow Transplantation.

Evaluation of Performance Status and Hematopoietic Cell Transplantation Specific Comorbidity Index on Unplanned Admission Rates in Patients with Multiple Myeloma Undergoing Outpatient Autologous Stem Cell Transplantation.

Although outpatient autologous stem cell transplantation (ASCT) is safe and feasible in most instances, some patients undergoing planned outpatient transplantation for multiple myeloma (MM) will need inpatient admission for transplantation-related complications. We aim to evaluate the difference, if any, between outpatient and inpatient ASCT cohorts of MM patients in terms of admission rate, transplantation outcome, and overall survival. We also plan to assess whether the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and Karnofsky Performance Status (KPS) can predict unplanned admissions after adjusting for confounding factors. Patients with MM (n = 448) who underwent transplantation at our institution between 2009 and 2014 were included in this retrospective analysis. Patients were grouped into 3 cohorts: cohort A, planned inpatient ASCT (n = 216); cohort B, unplanned inpatient admissions (n = 57); and cohort C, planned outpatient SCT (n = 175). The statistical approach included descriptive, bivariate, and survival analyses. There were no differences among the 3 cohorts in terms of type of myeloma, stage at diagnosis, time from diagnosis to transplantation, CD34 cell dose, engraftment kinetics, and 100-day response rates. Serum creatinine was higher and patients were relatively older in both the planned inpatient (median age, 62 years; range, 33 to 80 years) and unplanned (median age, 59 years; range, 44 to 69 years) admission cohorts compared with the outpatient-only cohort (median age, 57 years; range, 40 to 70 years) (P < .05). Performance status (cohort A: median, 90%; range, 60% to 100%; cohort B: 80%, 50% to 100%; cohort C: 80%, 60% to 100%) was lower (P < .05) and HCT-CI score (cohort A: median, 1.78; range, 0 to 8; cohort B: 2.67, 0 to 9; cohort C: 2.16, 0 to 7) was higher (P < .004) in both inpatient groups compared with the planned outpatient cohort. With a median follow up of 5 years, poor performance status (KPS <70%) appeared to be associated with worse survival (P < .002). HCT-CI >2 also appeared to be associated with worse outcomes compared with HCT-CI 0 to 1, the the difference did not reach statistical significance (hazard ratio, 1.41l 95% confidence interval, 0.72 to 2.76). Only 1 patient out of 448 died from a transplantation-related cause. Outpatient transplantation for myeloma is safe and feasible. In our experience, one-third of the patients undergoing outpatient transplantation needed to be admitted for transplantation-related toxicities. Patients in this group had lower preexisting KPS and higher HCT-CI scores. Whether planned admission for this group would have prevented unplanned admissions and undue stress on patients and the healthcare system should be tested in a prospective manner.

Wharton's Jelly-Derived Mesenchymal Stromal Cells as a Promising Cellular Therapeutic Strategy for the Management of Graft-versus-Host Disease.

Allogeneic hematopoietic cell transplantation (allo-HCT), a treatment option in hematologic malignancies and bone marrow failure syndromes, is frequently complicated by Graft-versus-host disease (GVHD). The primary treatment for GVHD involves immune suppression by glucocorticoids. However, patients are often refractory to the steroid therapy, and this results in a poor prognosis. Therefore alternative therapies are needed to treat GVHD. Here, we review data supporting the clinical investigation of a novel cellular therapy using Wharton's jelly (WJ)-derived mesenchymal stromal cells (MSCs) as a potentially safe and effective therapeutic strategy in the management of GVHD. Adult-derived sources of MSCs have demonstrated signals of efficacy in the management of GVHD. However, there are limitations, including: limited proliferation capacity; heterogeneity of cell sources; lengthy expansion time to clinical dose; expansion failure in vitro; and a painful, invasive, isolation procedure for the donor. Therefore, alternative MSC sources for cellular therapy are sought. The reviewed data suggests MSCs derived from WJ may be a safe and effective cellular therapy for GVHD. Laboratories investigated and defined the immune properties of WJ-MSCs for potential use in cellular therapy. These cells represent a more uniform cell population than bone marrow-derived MSCs, displaying robust immunosuppressive properties and lacking significant immunogenicity. They can be collected safely and painlessly from individuals at birth, rapidly expanded and stored cryogenically for later clinical use. Additionally, data we reviewed suggested licensing MSCs (activating MSCs by exposure to cytokines) to enhance effectiveness in treating GVHD. Therefore, WJCs should be tested as a second generation, relatively homogeneous allogeneic cell therapy for the treatment of GVHD.

Prophylactic use of zoledronic acid to prevent early bone loss is safe and feasible in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation.

Osteopenia and osteoporosis are well-known consequences of allogeneic stem cell transplantation (allo-SCT). The role of prophylactic zoledronic acid on bone turnover following allo-SCT has not been well characterized. We prospectively studied the role of prophylactic use of zoledronic acid on bone metabolism in 17 patients with acute myeloid leukemia (AML) undergoing allo-SCT over a period of three yr (2006-2009). We measured bone mineral density using dual energy X-ray absorptiometry (DXA) scanning and the markers of bone turnover by urinary N-terminal telopeptide (uNTX) and serum osteocalcin levels prior to and serially following transplantation. All patients received 4 mg of zoledronic acid (Zometa, Novartis Pharmaceuticals Corp., Basel, Switzerland) intravenously prior to starting conditioning regimen and at six months after SCT. DXA scores did not change significantly in any patient over time (p > 0.05). uNTX progressively decreased over time (p < 0.001) and serum osteocalcin stabilized after six months. No patient developed osteonecrosis of the jaw. In conclusion, in this prospective pilot study, prophylactic use of zoledronic acid to prevent early bone loss was found to be safe and feasible in patients with AML undergoing allo-SCT during the immediate post-transplantation period.

Is there a plateau in the survival curve after autologous transplantation in patients with intermediate and high-risk acute myeloid leukemia? A 20-year single institution experience.

In an attempt to examine whether autologous SCT provides long-term disease control in patients with intermediate and high-risk AML where a suitable donor is not available, we analyzed the outcomes of autologous SCT in patients with intermediate and high-risk AML from 1986 to 2005. No relapses occurred after 2.2 years. The overall survival curve appears to have developed a plateau after 2.2 years. In conclusion, autologous SCT in patients with AML in whom an allogeneic transplantation is not feasible appears to be a safe alternative and a plateau in the survival curve indicates cure in a small proportion of patients.

Autologous transplantation in patients with relapsed or high-grade follicular lymphoma provides long term disease-free survival and best median duration of response.

The best treatment option for patients with relapsed or high-grade follicular lymphoma (FL) is unknown. In spite of major advances in the therapy for FL, disease-free survival remains short, and median time to progression is just over a year. Autologous stem cell transplantation in patients with relapsed FL is safe and appears to improve disease-free survival. In an attempt to examine whether autologous stem cell transplantation provides long-term disease control in patients with relapsed or high-grade FL, we retrospectively evaluated our experience and analyzed the outcomes of autologous stem cell transplantation in patients with FL from 1991 to 2003. Seventeen men and seven women (n=24) of median age 47.5 years (range 28-64 years) were treated. Three patients with high-risk FL were in first remission. Twenty-one patients were salvaged after relapse with second-line chemotherapy. Of these, 14 were in CR at the time of transplantation, and seven patients were transplanted with active disease. Bone marrow was used in six patients as the source of stem cells prior to 1995 and peripheral blood stem cells were used in 18 patients. Twenty-three of 24 patients engrafted (96%). Median time for neutrophil recovery was 11.5 days (range 9-35 days) and 15 days (range 10-40 days) for platelets. Median duration of follow-up was 6 years (range 7 months-8 years). Of the 24 patients, six have died-with one patient death due to transplant-related pulmonary complications. Overall survival (OS) and disease-free survival (DFS) of all evaluable patients were 71.6 and 40%, respectively. Median duration of response was 4.3 years. OS and DFS in patients transplanted in CR were 80 and 57%, respectively. For those transplanted with disease, a complete response was achieved in 43% of patients, with the OS and DFS of 57 and 19%, respectively. Disease status at transplantation was not a significant variable for survival (p>0.3). Three patients developed moderate to severe treatment-related toxicity, two with grade III mucositis and one with life-threatening infection. When these results are compared with historical controls or patients treated with other modalities, autologous stem cell transplantation appears to be providing the longest disease-free survival and best duration of response.