Autologous Hematopoietic Stem Cell Transplantation Group Research Articles

Autologous hematopoietic stem cell transplantation improves survival outcomes in peripheral T-cell lymphomas: a multicenter retrospective real-world study

The aim of this study is to evaluate the survival benefit of consolidative autologous hematopoietic stem cell transplantation (ASCT) in patients with peripheral T-cell lymphomas (PTCL). In this retrospective study, the ASCT group underwent consolidative ASCT after first-line therapy at 14 transplantation centers in China between January 2001 and December 2019. Data were collected over the same time frame for the non-ASCT group from the database of lymphoma patient records at Peking University Cancer Hospital & Institute. A total of 120 and 317 patients were enrolled in the ASCT and non-ASCT groups, respectively, and their median ages were 43 years and 51 years, respectively. In the ASCT group, 101 patients had achieved complete remission (CR) and 19 patients had achieved partial remission at the time of ASCT. The median follow-up time was 40.2 months and 68 months, and the 3-year overall survival (OS) rate was 80.6% and 48.9% (p < 0.001) for the ASCT and non-ASCT groups, respectively. The beneficial effect of ASCT for OS remained even after propensity score-matched (PSM) analysis (81.6% vs 68.3%, p = 0.001). Among the 203 patients who were aged ≤ 65 years and achieved CR, ASCT conferred a significant survival benefit (3-year progression-free survival [PFS]: 67.4% vs 47.0%, p = 0.004; 3-year OS: 84.0% vs 74.1%, p = 0.010), and this was also maintained after PSM analysis (3-year PFS: 66.6% vs 48.4%, p = 0.042; 3-year OS: 84.8% vs 70.5%, p = 0.011). Consolidative ASCT improved the survival outcome of PTCL patients, even those who achieved CR after first-line therapy.

Outcomes in progressive systemic sclerosis treated with autologous hematopoietic stem cell transplantation compared with combination therapy.

Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve long-term survival for early diffuse progressive SSc compared with CYC. CYC, however, does not provide a long-term benefit in SSc. The combination of MMF and rituximab is a potent alternative regimen. We aimed to retrospectively compare the outcomes of SSc patients who underwent AHSCT to patients who met the eligibility criteria for AHSCT but received upfront combination therapy with MMF and rituximab. Repeated assessments of modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity (DLCO) values were conducted. Clinical improvement was defined as an mRSS decrease >25% or an FVC increase >10%. Event-free survival (EFS) was defined in the absence of persistent major organ failure or death. Twenty-one SSc patients in the combination therapy group were compared with 16 in the AHSCT group. Age, sex and disease duration were similar between the two groups. Clinical improvement at 12 months was seen in 18 (86%) patients in the combination group compared with 13 (81%) in the AHSCT group (P = 0.7). The hazard ratio for EFS at 24 months favoured the combination group (HR = 0.09, P = 0.04). During follow-up, both groups exhibited a significant and comparable reduction in mRSS and an increase in FVC values at each time interval up to 24 months. MMF and rituximab compared with AHSCT in SSc patients eligible for AHSCT resulted in similar skin and lung clinical improvement with a better safety profile at 24 months.

Estimating the Incidence-Based Cost of Illness Due to Hematopoietic Stem Cell Transplantation Using One-Year Insurance Claim Data in Korea.

Long-term follow-up data are required for incidence-based cost-of-illness (COI) studies, and it is difficult to carry out such assessments. To overcome this limitation, we estimated the acute and maintenance-state costs of hematopoietic stem cell transplantation (HSCT) using 1-year claim data. Using Korean National Health Insurance (NHI) data from 2016, 2017, and 2018, we identified patients receiving HSCT based on the procedure code "X5*" (i.e., HSCT). The post-HSCT group was defined as patients without the "X5*" code, but with the code "Z948 (other transplanted conditions)" and indications of HSCT (referring to those who had received HSCT). Mean annual medical use and costs were computed using the monthly values available for each patient. The mean number of hospitalizations/year, outpatient visits per year, hospitalization days/year, and length of stay (LOS)/hospitalization were 8.14, 35.80, 97.16, and 14.72, respectively, for allogeneic HSCT patients (n = 56); 8.08, 33.58, 73.04, and 10.63, respectively, for autologous HSCT patients (n = 89); 2.93, 29.40, 50.95, and 20.84, respectively, for post-allogeneic HSCT patients (n = 40); and 1.72, 16.38, 30.11, and 19.29, respectively, for post-autologous HSCT patients (n = 252). The estimated annual NHI-covered medical costs (US dollars) were $38,833-$40,876 for the allogeneic HSCT group, $1749-$6744 for the post-allogeneic HSCT group, $21,231-$22,863 for the autologous HSCT group, and $3954-$5352 for the post-autologous HSCT group. This study describes an alternative method for conducting incidence-based COI studies using cross-sectional claims data.

Financial incentives to increase stool collection rates for microbiome studies in adult bone marrow transplant patients.

In order to study the role of the microbiome in hematopoietic stem cell transplantation (HCT), researchers collect stool samples from patients at various time points throughout HCT. However, stool collection requires active subject participation and may be limited by patient reluctance to handling stool. We performed a prospective study on the impact of financial incentives on stool collection rates. The intervention group consisted of allogeneic HCT patients from 05/2017-05/2018 who were compensated with a $10 gas gift card for each stool sample. The intervention group was compared to a historical control group of allogeneic HCT patients from 11/2016-05/2017 who provided stool samples before the incentive was implemented. To control for possible changes in collections over time, we also compared a contemporaneous control group of autologous HCT patients from 05/2017-05/2018 with a historical control group of autologous HCT patients from 11/2016-05/2017; neither autologous HCT group was compensated. The collection rate was defined as the number of samples provided divided by the number of time points we attempted to obtain stool. There were 35 allogeneic HCT patients in the intervention group, 19 allogeneic HCT patients in the historical control group, 142 autologous HCT patients in the contemporaneous control group (that did not receive a financial incentive), and 75 autologous HCT patients in the historical control group. Allogeneic HCT patients in the intervention group had significantly higher average overall collection rates when compared to the historical control group allogeneic HCT patients (80% vs 37%, p<0.0001). There were no significant differences in overall average collection rates between the autologous HCT patients in the contemporaneous control and historical control groups (36% vs 32%, p = 0.2760). Our results demonstrate that a modest incentive can significantly increase collection rates. These results may help to inform the design of future studies involving stool collection.

Chimeric antigen receptor T‐cell therapy combined with autologous stem cell transplantation improved progression‐free survival of relapsed or refractory diffuse large B‐cell lymphoma patients: A single‐center, retrospective, cohort study

Autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CART) are salvage therapies that are utilised for treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, whether the combination therapy of ASCT and CART (ASCT-CART) can improve the survival of R/R DLBCL remains unknown. Overall, 67R/R DLBCL patients were included, among which 21 patients underwent ASCT-CART therapy and 46 patients underwent ASCT therapy. The median number of mononuclear cells numbers that were infused in the ASCT-CART and ASCT groups was 4.71×108 /kg and 5.36×108 /kg, respectively (p=0.469). The median number of CD34+ cell numbers that were infused in the ASCT-CART and ASCT groups was 2.41×106 /kg and 3.05×106 /kg, respectively (p=0.663). The median number of CART cells that were infused was 2.63×106 /kg with a median transduction rate of 59.83%. The objective response rates to ASCT-CART and ASCT therapy were 90% and 89%, respectively (p=1.000). However, the ASCT-CART group showed higher complete remission (CR) rates than the ASCT group (71% vs. 33%; p=0.003). The ASCT-CART group demonstrated superior 3year progression-free survival (PFS) (80% vs. 44%; p=0.036) and lower 3year relapse/progression rate (15% vs. 56%; p=0.015) compared to the ASCT group. However, the 3year overall survival results indicated that there were no differences between the two groups (80% vs. 69%; p=0.545). For R/R DLBCL patients, ASCT-CART therapy is associated with higher CR rate, better PFS, and lower relapse/progression rate. These data support that ASCT-CART therapy can be used as a salvage therapy for R/R DLBCL patients.

A Propensity Score Matching Study of Autologous Hematopoietic Stem Cell Transplantation and New Drug Chemotherapy for Newly Diagnosed Multiple Myeloma

To compare the clinical efficacy, survival, and prognosis of autologous hematopoietic stem cell transplantation (ASCT) with new drug chemotherapy in the treatment of newly diagnosed multiple myeloma (NDMM) in the new drug era. The clinical data of 149 patients with NDMM treated with new drug induction regimen in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2012 to December 2019 were retrospectively analyzed. Twenty-four patients who received ASCT were in ASCT group, and 125 patients who did not receive ASCT were in non-ASCT group. The median follow-up time was 43 (1-90) months. The propensity score matching (PSM) method was used to balance confounding factors, then depth of response, overall survival (OS), and progression-free survival (PFS) between the two groups were compared and subgroup analysis was performed. After matching, the covariates were balanced between the two groups. Fifty-one patients (15 cases in ASCT group and 36 cases in non-ASCT group) were included. ASCT patients had a better complete response (CR) rate than non-ASCT patients receiving maintenance therapy (93.3% vs 42.3%, P=0.004), while there were no statistical differences in deep response rate and overall response rate (ORR) between the two groups (93.3% vs 65.4%, P=0.103; 93.3% vs 96.2%, P=1.000). Before matching, the 3 and 5-year PFS rate and median PFS (mPFS) in ASCT group and non-ASCT group were [89.6% vs 66.5%, P=0.024; 69.8% vs 42.7%; non-response (NR) vs 51.0 months], and the 3 and 5-year OS rate and median OS (mOS) were (100% vs 70.6%, P=0.002; 92.3% vs 49.6%; NR vs 54.0 months). After matching, the 3 and 5-year PFS rate and mPFS in ASCT group and non-ASCT group were (83.6% vs 61.7%, P=0.182; 62.7% vs 45.7%; NR vs 51.0 months), the 3 and 5-year OS rate and mOS were (100% vs 65.6%, P=0.018; 88.9% vs 46.9%; NR vs 51.0 months). Subgroup analysis showed that patients with mSMART 3.0 high risk stratification, the 3-year PFS rate and mPFS in ASCT group and non-ASCT group were (83.3% vs 41.5%, P=0.091; NR vs 34.0 months), and the 3-year OS rate and mOS were (100% vs 41.5%, P=0.034; NR vs 34.0 months). Patients with mSMART 3.0 standard risk stratification, the 3-year PFS rate and OS rate in ASCT group and non-ASCT group were (83.3% vs 76.8%, P=0.672; 100% vs 87.2%, P=0.155). The 3-year PFS and OS rate in MM patients who achieved deep response within 3 months after transplantation compared with non-ASCT patients who achieved deep response after receiving maintenance therapy were (83.1% vs 56.7%, P=0.323; 100% vs 60.5%, P=0.042), and the 3-year PFS and OS rate in patients who achieved overall response in both groups were (83.1% vs 62.5%, P=0.433; 100% vs 68.1%, P=0.082). After matching, Cox multivariate regression analysis showed that mSMART 3.0 risk stratification and ASCT were independent prognostic factors for OS. In the new drug era, ASCT can increase CR rate and prolong OS of NDMM patients. ASCT patients who are mSMART 3.0 high risk stratification or achieved deep response within 3 months after transplantation have better OS than non-ASCT patients receiving new drug chemotherapy. ASCT and mSMART 3.0 risk stratification are independent prognostic factors for OS in NDMM patients.

Long Term Follow up after Adoptive Transfer of CD19-Specific CAR+ T Cells Genetically Modified Via Non-Viral Sleeping Beauty S ystem Following Hematopoietic Stem Cell Transplantation (HSCT)

BACKGROUND. We evaluated a human application of T cells genetically modified using the Sleeping Beauty (SB) transposon/transposase system to express a CD19-specific chimeric antigen receptor (CAR, designated CD19RCD28). The SB system uses a synthetic DNA transposon for nonviral somatic gene transfer. The initial data were reported (J Clin Invest. 2016 Sep 1;126(9):3363-76) and we now present long-term follow-up (LTFU).METHODS. T cells were genetically modified using DNA plasmids from the SB platform to stably express CD19RCD28 and selectively propagated ex vivo with activating and propagating cells (AaPC) with cytokines. Twenty-six patients with advanced non-Hodgkin lymphoma (n=9) or acute lymphoblastic leukemia (n=17) underwent autologous (n=7) or allogeneic (n=19) HSCT followed by a T-cell infusion as adjuvant therapy on two clinical trials NCT00968760 and NCT01497184, respectively. Patients were subsequently enrolled onto a LTFU study, NCT01492036, to be followed for up to 15 years. During this time, patients could be tested annually for the persistence of genetically modified T cells using PCR and flow cytometry.RESULTS. The persistence of SB-modified T cells was measured in two of the seven autologous HSCT/CAR+T patients as long as 4-years post infusion and both remain progression-free. Similarly, CAR expression was detected in three allogeneic HSCT recipients one-year post T-cell infusion with no disease progression. Upon LTFU of the autologous HSCT group, six of seven patients continue in complete remission (CR) at a median of 3.4 years (range: 1.7 to 4.2 years). The 3-year progression-free (PFS) and overall survival (OS) rates are 86% and 100%, respectively (Figure). After allogeneic HSCT, recipients received donor-derived CAR+ T cells (8 haploidentical, 10 matched-sibling, one 1Ag-mismatched sibling). For this allogeneic group, six patients remain alive and in CR following haplo (n=4) or matched sibling donor (n=2) HSCT with a median follow-up of 1.5 years (range: 0.003 to 2.9 years). The 2-year PFS and OS rates are 45% and 49%, respectively (Figure). Additionally, the 2-year PFS and OS rates for haplo-identical transplants were 57% and 71%, respectively. No long-term safety issues were identified; specifically, no graft failure or excess graft-versus-host-disease.CONCLUSIONS. CD19-specific CAR+ T cells could be detected and were well-tolerated years after adoptive transfer and appear to provide long-term cancer control when infused after HSCT for patients with advanced disease. These encouraging results support further clinical development of this non-viral gene therapy approach.Figure: Overall and progression-free survivals of recipients of SB-modified CAR+ T cells after autologous and allogeneic HSCT. [Display omitted] DisclosuresHuls:Former employee of Intrexon: Employment. De Groot:Ziopharm: Employment. Smith:Ziopharm: Employment. Yang:Ziopharm: Employment. Kantarjian:Bristol-Meyers Squibb: Research Funding; Novartis: Research Funding; Delta-Fly Pharma: Research Funding; Amgen: Research Funding; ARIAD: Research Funding; Pfizer: Research Funding. Cooper:Immatics: Equity Ownership, Patents & Royalties, Research Funding; Intrexon Corporation: Equity Ownership, Patents & Royalties; Sangamo Biosciences: Patents & Royalties; Organovo Holdings: Equity Ownership; Ziopharm: Employment, Equity Ownership, Research Funding; Procter & Gamble: Equity Ownership; Miltenyi Biotec: Honoraria; Ampliphi Biosciences: Equity Ownership; Argos Therapeutics: Equity Ownership; Ferring: Consultancy; Targazyme, Inc.: Equity Ownership.

Safety of Alemtuzumab and Autologous Hematopoietic Stem Cell Transplantation Compared to Noninduction Therapies for Multiple Sclerosis.

ObjectiveTo assess safety outcomes for the induction therapies alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT) compared to noninduction disease-modifying therapies.MethodsWe performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national health care registers. Alemtuzumab, AHSCT, and a matched reference group of noninduction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. Main outcomes were death, thyroid disease, nonthyroid autoimmune disease, and infection.ResultsWe identified 132 alemtuzumab-treated and 139 AHSCT-treated (68% high-dose cyclophosphamide and anti-thymocyte globulin [ATG], 32% BCNU, etoposide, cytosine-arabinoside, and melphalan/ATG) patients, together with 2,486 matched patients treated with noninduction therapies. Four patients in the alemtuzumab group died (incidence rate [IR] per 1,000 person-years 8.6, 95% confidence interval [CI] 2.3–22.0) compared to 1 patient in the AHSCT group (IR 1.7, 95% CI 0.0–9.6), and the mortality rate in the reference group was 0.7 (95% CI 0.3–1.3). Thyroid disease was most frequent in the alemtuzumab group (IR 109, 95% CI 75–154) but also occurred more often for AHSCT (IR 34, 95% CI 18–56) compared to the reference (IR 5.3 95% CI 3.9–7.1). The incidence of nonthyroid autoimmune disease was similar in all groups. IR for infection diagnosed ≥6 months from therapy initiation was 53 (95% CI 30–87) for alemtuzumab, 108 (95% CI 75–150) for AHSCT, and 51 (95% CI 46–57) for the reference.ConclusionWe confirmed a high incidence of thyroid disease in alemtuzumab- and, to a smaller extent, AHSCT-treated patients and found a higher incidence of infection for AHSCT compared to both alemtuzumab and noninduction therapies. The incidence of nonthyroid autoimmune disease was low for both therapies.Classification of EvidenceThis study provides Class III evidence of an increased risk of thyroid disease with alemtuzumab and an increased risk of infection with AHSCT treatment.

Association of Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis With Marked Improvement in Health-Related Quality of Life.

To quantify the magnitude, domains, and duration of change in health-related quality of life (HRQoL) in patients with systemic sclerosis (SSc) who underwent autologous hematopoietic stem cell transplantation (HSCT) as compared to SSc patients with similar characteristics who did not undergo autologous HSCT. The study was designed as a retrospective study comparing SSc patients who underwent autologous HSCT and SSc patients who met the criteria for transplantation but were treated with conventional care. Outcomes included scores on the 36-item Short Form (SF-36) health survey and the Health Assessment Questionnaire (HAQ) and its disease-specific symptom scales. Differences in scores between the groups were compared using linear models, adjusting for baseline scores and inverse probability of treatment and censoring weights. In total, 41 SSc patients who underwent autologous HSCT and 65 SSc patients treated with conventional care were compared. In marginal linear weighted models, the SF-36 physical component summary score was a mean ± SEM 7.02 ± 1.94 points higher at the first annual visit (P = 0.001) and 14.40 ± 6.16 points higher at the seventh annual visit (P = 0.03) in patients treated with autologous HSCT compared to the conventional care group. HAQ scores were significantly better in the autologous HSCT group compared to the conventional care group during follow-up (mean ± SEM difference from baseline -0.57 ± 0.13 [P < 0.001] at the first annual visit and -0.94 ± 0.49 [P = 0.07] at the seventh annual visit). There were no differences in the SF-36 mental component summary scores between the 2 groups either at baseline or during follow-up. This study provides robust complementary HRQoL data, including overall and event-free survival data, to expand on the standard repertoire of biomedical variables, thus potentially supporting the physical benefits of autologous HSCT in patients with SSc.

Upfront autologous hematopoietic stem cell transplantation in patients with high-risk stage III to IV Hodgkin lymphoma: a multicenter retrospective cohort study

ABSTRACTBackground/Objective: Nearly 30% of patients with advanced-stage Hodgkin lymphoma (HL) are not cured. We should better control tumors with initial treatment for patients with advanced stage HL whose interim positron emission tomography/computed tomography (PET/CT) was positive. The objective of our study was to confirm the superiority of autologous hematopoietic stem cell transplantation (ASCT) therapy in these patients.Methods: Eighty-nine HL patients with stage III-IV, international prognostic score (IPS) ≥3 and Deauville more than 3° at the interim PET/CT were analyzed. Forty five patients received ASCT. The other 44 patients received two cycles DHAP chemotherapy.Results: The 3-year overall survival (OS) of patients who received ASCT was 91.1%, and for the patients who received chemotherapy, it was 72.7% (P = 0.025). The 3-year progression free survival (PFS) of patients in the ASCT group was 88.9%, but for patients in the chemotherapy group, it was only 70.5%(P = 0.017). No patient died of toxicity from ASCT. Additionally, there was no difference in the rates of secondary malignancies between the ASCT and chemotherapy groups. Extranodal and bone marrow involvement were poor prognostic factors, while ASCT was a good prognostic factor.Conclusion: The use of ASCT as a first-line consolidation treatment could improve outcome of patients with advanced-stage high risk HL whose interim PET/CT was positive.

The different roles of molecular classification according to upfront autologous stem cell transplantation in advanced-stage diffuse large B cell lymphoma patients with elevated serum lactate dehydrogenase.

The non-germinal center B cell (non-GCB) subtype of diffuse large B cell lymphoma (DLBCL) is more related to poor prognosis than the GCB subtype. To investigate the role of molecular classification according to upfront autologous hematopoietic stem cell transplantation (ASCT), we retrospectively evaluated 219 newly diagnosed high-risk DLBCL patients. Eighty-one patients were in the ASCT group, and 138 patients were in the non-ASCT group. The ASCT group yielded significantly better overall survival (OS) and progression-free survival (PFS) than the non-ASCT group (p=0.038 and p=0.007), and patients with the non-GCB subtype were more related to inferior PFS than those with the GCB subtype (p=0.020). After performing age-matching by using propensity scores, upfront ASCT continued to show better OS and PFS than non-ASCT (p=0.046 and p=0.026). In the non-ASCT group, the non-GCB subtype showed worse OS and PFS than the GCB subtype (p=0.039 and p=0.007). Patients who achieved complete response showed differences in OS and PFS according to molecular subtype (p=0.007 and p=0.002). In the ASCT group, there were no significant differences in OS and PFS according to molecular classification (p=0.277 and p=0.892). In conclusion, non-GCB subtype DLBCL patients showed poor OS and PFS in the non-ASCT group while they did not show clinical significance in the ASCT group. This suggests the possibility that upfront ASCT may improve the poor prognosis of non-GCB subtype in high-risk DLBCL.

Retrospective analysis on therapeutic effect of autologous hematopoietic stem cell transplantation in multiple myeloma patients

To evaluate the efficacy and prognostic factors of autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Retrospective analysis was performed in 27 MM patients undergoing ASCT at our hospital from May 2004 to August 2011. After comparing with 28 patients achieving very good partial response (VGPR) or better outcome and not undergoing ASCT, the impact on the extent of response, progression-free survival (PFS) and overall survival (OS) as well as related prognostic factors of MM patients were analyzed. All patients successfully underwent hematopoietic reconstruction without transplantation-related mortality. The complete remission (CR) rate of ASCT group increased from 25.9% (7/27) at pre-ASCT to 70.4% (19/27) at post-ASCT (P < 0.01). The estimated 5-year rate of progression-free survival was 56.2% (median not reached) in the ASCT group and 24.9% (median 29 months) in the non-ASCT group (P < 0.05). The 5-year probability of overall survival was 52.2% (median not reached) in the ASCT group and 33.1% (median 60 months) in the non-ASCT group (P > 0.05). Univariate analysis in ASCT group demonstrated that maintenance/consolidation therapy was associated with PFS (P = 0.010) and OS (P = 0.008).Patients on induction therapy containing bortezomib and early ASCT maintenance therapy all survived without disease progression until final follow-up (P = 0.010). ASCT can further increase the CR rate, prolong PFS and probably OS. The incorporation of novel agents into induction, consolidation and maintenance phases has optimized the anti-myeloma activity of ASCT and may be important for improved long-term outcomes.

Performance Status and Quality Life of Patients with Hematopoietic Stem Cell Transplantation According to Period of Survival

Purpose: The purpose of this study was to identify the performance status and quality of life (QOL) of patients after hematopoietic stem cell transplantation (HSCT) according to period of survival. Methods: Participants consists of 83 HSCT patients who were being treated regularly at out-patient clinic in two general hospitals in D city. Data were collected using questionnaires that were modified by Functional Assessment of Cancer Therapy-Bone Marrow Transplabtation (FACT-BMT) scale and Eastern Cooperative Oncology Group (ECOG). Results: The unrelated HSCT group’s survival period was significantly worse than related HSCT group and autologous HSCT group. Performance status of the group with more than 3 years survival was significantly higher than that of the group with less than a year survival. The mean score of total QOL of HSCT patients was 2.69 out of 4. Total QOL was not significantly different among period of survival less than 1 year, 1-3 years, and more than 3 years. But BMT QOL was shown that the group with more than 3 years survival was higher than the groups with less than a year survival. Conclusion: Performance status and BMT QOL of the group with less than 1 year survival was significantly lowered than the groups with more than 3 years survival.

Autologous Hematopoietic Stem Cell Transplantation (HCT) is a Safe and Effective Treatment for Primary Plasma Cell Leukemia: The CIBMTR Experience.

Abstract 532Primary Plasma cell leukemia (PCL) is a rare plasma cell disorder characterized by an aggressive clinical course. The efficacy of autologous and allogeneic HCT in PCL is uncertain due to the small number of patients that have been reported in the literature. To determine the potential for long-term disease control using HCT in PCL, we performed a retrospective review of 160 patients with primary PCL who received autologous (n=107), allogeneic (n=52) or syngeneic (n=1) HCT and were reported to the CIBMTR between 1995 and 2006. Kaplan–Meier analysis was used for overall survival (OS) and progression free survival (PFS). Cumulative incidence estimates of non-relapse mortality (NRM), relapse, acute and chronic GVHD were calculated.Median age at the time of autologous HCT was 57 years (range, 32-74 years) and allogeneic HCT was 48 years (range, 24-62 years). Median time from initial treatment to autologous HCT was 7 months and allogeneic HCT was 6 months. At the time of transplant, in the autologous HCT group, 19% patients were in complete remission, 56% in partial remission and 1% had relapsed/progressive disease; in the allogeneic HCT group, 17% were in complete remission, 46% in partial remission and 10% had relapsed/progressive disease. In the allogeneic HCT group, 83% of the patients received myeloablative conditioning regimens and 17% received nonmyeloablative/reduced-intensity conditioning. The rate of acute GVHD was 35% (95% confidence interval [CI], 22%-49%) and the rate of chronic GVHD at 3 years was 27% (95% CI, 13%-40%). After a median follow-up of 38 months, 20 of the 52 patients (38%) are alive in the allogeneic HCT group and 68 of the 107 pts (64%) are alive in the autologous HCT group (Figure 1). Progressive disease accounted for 38% of the deaths in the allogeneic HCT group and 86% of the deaths in the autologous HCT group. The outcomes are summarized in table 1. The remarkable overall survival of patients after autologous HCT in this analysis is noteworthy and indicates that autologous HCT is a safe and acceptable treatment option for patients with primary PCL. Although relapse rates are lower, allogeneic HCT carries a much higher risk of NRM and should be considered primarily in the context of a clinical trial.Table 1OutcomesAllogeneic Probability (95% CI)Autologous Probability (95% CI)TRM @ 1 year26 (15 - 39)2 (0 - 5)TRM @ 3 years40 (27 - 55)5 (1 - 10)Relapse @ 3 years40 (26 - 54)61 (49 - 72)PFS @ 3 years20 (10 - 33)34 (24 - 46)OS @ 3 years39 (25 - 53)62 (51 - 73) [Display omitted] Disclosures:Lonial: Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.

Outcomes of Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL).

Considerable advancements have been made in our understanding of the biology and treatment of CLL/SLL. Despite these advances, CLL/SLL essentially remains an incurable illness. Hematopoietic stem cell transplantation (HSCT) has been used in an attempt to improve remission duration and survival. However little high level data exists on outcomes for patients (pts) undergoing HSCT for CLL/SLL. We evaluated the long-term survival of 65 CLL/SLL pts who underwent allogeneic or autologous HSCT from 1995 until 2006 at the University of Nebraska Medical Center. The median duration of follow-up for surviving pts is 8.8 years. The median age was 49 years and there was no significant difference in age between the autologous and allogeneic groups. Thirty nine pts underwent allogeneic HSCT (n=25 matched related donor, n=14 matched unrelated donor) and 26 pts underwent autologous HSCT. For the group undergoing allogeneic HSCT, the stem cell source was mobilized peripheral blood progenitor cells in 74% and bone marrow in 26%. In the autologous HSCT group, 81% of pts received peripheral blood and 19% received bone marrow as their stem cell source. In the autologous group there were 19 deaths (10 from progression) over the period of follow-up. In the allogeneic group there were 29 deaths (including 8 from acute regimen related toxicity, 9 from infection, 3 from complications of GVHD, 1 from late pulmonary toxicity, one from PTLD, one from MDS/AML) and 10 pts are alive at end of follow-up. One hundred day mortality was significantly higher in the allogeneic group (20% vs. 6%; p=0.05). For the allogeneic group the cumulative incidence of grade II-IV acute graft versus host disease (GHVD) was 64% (95% confidence interval [CI]=47–76) and the cumulative incidence of chronic extensive GHVD was 50% (95% CI=29–68). One-year progression free survival (PFS) was significantly better among autologous SCT when compared to allogeneic HSCT (77% versus 45%; P=0.006), but at 5 years these differences were no longer apparent. Similarly, one-year overall survival (OS) was significantly better for autologous SCT (81% versus 48%; P=0.003) but at 5 years these differences were no longer significant (49% versus 31%; p=0.15). Among all patients undergoing allogeneic HSCT, 5-year PFS was significantly higher for patients with SLL vs. CLL (36% vs. 25%; P=0.04). In addition, 5 year OS was better for pts with SLL compared to CLL (51% vs. 33%, P=0.06). There was no difference in PFS or OS following autologous SCT between patients with a diagnosis of CLL versus SLL. The group of pts undergoing autologous HSCT demonstrates no plateau on the PFS curve, whereas for pts undergoing allogeneic HSCT there is a suggestion of a plateau in PFS at approximately 25%. In conclusion, CLL/SLL patients undergoing allogeneic SCT had a higher incidence of early treatment related mortality, mainly from regimen related toxicity and infection. In a subgroup analysis pts with CLL appear to have an inferior PFS compared with pts with SLL. This difference may be due to a more prominent underlying immune deficiency in CLL patients that leads to a higher probability of treatment related mortality. Pts with CLL/SLL undergoing autologous HSCT had a lower incidence of treatment related mortality, but there is no evidence of a plateau in progression-free survival.

Postremission therapy for acute myeloid leukemia in the first remission

The medical records of 99 patients with acute myeloid leukemia (AML; except AML, M3) in the first remission from 1995 to 2004 were retrospectively reviewed. When they achieved complete remission, at first complete remission (CR1), patients received allogeneic (n = 23), autologous hematopoietic stem cell transplantation (HSCT) (n = 35), or intensive chemotherapy (n = 41) according to prognostic factors and donor availability. There was an advantage in terms of event-free survival (EFS, p = 0.0001) and overall survival (OS, p = 0.0002) with HSCT as compared to those of intensive chemotherapy. However, the EFS and OS were not different between allogeneic HSCT and autologous HSCT. In high-risk patients, the EFS and OS of allogenic or autologous HSCT group were higher compared with those in the intensive chemotherapy group (p < 0.01). However, there was no difference between allogeneic HSCT and autologous HSCT in terms of EFS and OS. In the intermediate- or low-risk group, there was no significant difference in the outcome according to the postremission modalities.

Treatment of Hematologic Malignancies with Alternate Hemibody Irradiation Combined with High-Dose Chemotherapy: A Single-Center Experience

The objective of this study was to evaluate the clinical outcome of the treatment of hematologic malignancies with alternate hemibody irradiation (AHBI) combined with high-dose chemotherapy. Seventeen patients with hematologic malignancies were treated with AHBI combined with high-dose chemotherapy. Following high-dose chemotherapy, upper hemibody irradiation (UHBI) and lower hemibody irradiation (LHBI) were given sequentially in a dose of 6 to 9 Gy. UHBI was given 14 days (range, 12-22 days) after high-dose chemotherapy, and LHBI was performed 23 days (range, 7-34 days) after UHBI. Meanwhile, we treated a control group of 14 patients with acute lymphoblastic leukemia (ALL) with autologous hematopoietic stem cell transplantation (AHSCT). Hematopoietic reconstitution was observed in all of the patients. The median follow-up period was 927 days (range, 428-1446 days). The 3-year probabilities of disease-free survival (DFS) were 52.38% +/- 13.47% for the patients in complete remission who underwent AHBI. No patient died of AHBI-related toxicity. The 3-year DFS rates for the 2 groups of patients with ALL were not significantly different (47.73% +/- 17.55% in the AHBI group and 53.88% +/- 14.08% in the AHSCT group; P > .05). AHBI combined with high-dose chemotherapy is a feasible approach for patients with hematologic malignancies and has the advantages of a desirable effectiveness, low costs, simple operation, and acceptable side effects.