Edward A Stadtmauer

University of Pennsylvania, Philadelphia, Pennsylvania, United States

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Publications (197)1395.18 Total impact

  • Bone marrow transplantation. 07/2014;
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    ABSTRACT: The success of hematopoietic stem-cell transplantation (HSCT) with reduced-intensity conditioning (RIC) is limited by a high rate of disease relapse. Early risk assessment could potentially improve outcomes by identifying appropriate patients for pre-emptive strategies that may ameliorate this high risk. Using a series of landmark analyses, we investigated the predictive value of early (day-30) donor chimerism measurements on disease relapse, graft-versus-host disease and survival in a cohort of 121 patients who were allografted with a uniform RIC regimen. Chimerism levels were analyzed as continuous variables. In multivariate analysis, day-30 whole blood chimerism levels were significantly associated with relapse (HR=0.90, p<0.001), relapse-free survival (HR=0.89, p<0.001) and overall survival (HR=0.94, p=0.01). Day-30 T-cell chimerism levels were also significantly associated with relapse (HR=0.97, p=0.002), relapse-free survival (HR=0.97, p<0.001) and overall survival (HR=0.99, p=0.05). Multivariate models that included T-cell chimerism provided a better prediction for these outcomes compared to whole blood chimerism. Day-30 chimerism levels were not associated with acute or chronic graft-versus-host disease. We found that high donor chimerism levels were significantly associated with a low lymphocyte count in the recipient prior to transplant, highlighting the impact of pre-transplant lymphopenia on the kinetics of engraftment after RIC HSCT. In summary, low donor chimerism levels are associated with relapse and mortality and can potentially be used as an early predictive and prognostic marker. These findings can be used to design novel approaches to prevent relapse and to improve survival after RIC HSCT.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2014; · 3.15 Impact Factor
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    ABSTRACT: The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy.
    Autophagy 05/2014; 10(8). · 12.04 Impact Factor
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    ABSTRACT: Allogeneic hematopoietic cell transplantation (alloHCT) with reduced intensity conditioning is an appealing option for patients with high risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1-21 of 28 days cycles, with intra-patient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age 54 years) with high risk MM were enrolled at 8 centers between 2009 -2012. The median time from alloHCT to LEN initiation was 96 days (66-171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%).Most common reasons for discontinuation were aGVHD (37%) and disease progression (37%). Cumulative incidence of grades III-IV acute GVHD from time of initiation of Len was 17%. . Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplant related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN post alloHCT is feasible at lower doses, although associated with a 38% incidence of aGVHD. Survival outcomes observed in this high risk MM population warrant further study of this approach.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2014; · 3.15 Impact Factor
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    ABSTRACT: Myeloma-directed cellular immune responses after autologous stem cell transplantation (ASCT) may reduce relapse rates. We studied whether coinjecting the TLR-3 agonist and vaccine adjuvant Poly-ICLC with a MAGE-A3 peptide vaccine was safe and would elicit a high frequency of vaccine-directed immune responses when combined with vaccine-primed and costimulated autologous T cells.EXPERIMENTAL DESIGN: In a phase II clinical trial (NCT01245673), we evaluated the safety and activity of ex vivo expanded autologous T cells primed in vivo using a MAGE-A3 multipeptide vaccine (compound GL-0817) combined with Poly-ICLC (Hiltonol), granulocyte macrophage colony-stimulating factor (GM-CSF) ± montanide. Twenty-seven patients with active and/or high-risk myeloma received autografts followed by anti-CD3/anti-CD28-costimulated autologous T cells, accompanied by MAGE-A3 peptide immunizations before T-cell collection and five times after ASCT. Immune responses to the vaccine were evaluated by cytokine production (all patients), dextramer binding to CD8(+) T cells, and ELISA performed serially after transplant.RESULTS: T-cell infusions were well tolerated, whereas vaccine injection site reactions occurred in >90% of patients. Two of nine patients who received montanide developed sterile abscesses; however, this did not occur in the 18 patients who did not receive montanide. Dextramer staining demonstrated MAGE-A3-specific CD8 T cells in 7 of 8 evaluable HLA-A2(+) patients (88%), whereas vaccine-specific cytokine-producing T cells were generated in 19 of 25 patients (76%). Antibody responses developed in 7 of 9 patients (78%) who received montanide and only weakly in 2 of 18 patients (11%) who did not. The 2-year overall survival was 74% [95% confidence interval (CI), 54%-100%] and 2-year event-free survival was 56% (95% CI, 37%-85%).CONCLUSIONS: A high frequency of vaccine-specific T-cell responses were generated after transplant by combining costimulated autologous T cells with a Poly-ICLC/GM-CSF-primed MAGE-A3 vaccine. Clin Cancer Res; 1-11. ©2013 AACR.
    Clinical Cancer Research 02/2014; · 7.84 Impact Factor
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    ABSTRACT: Allogeneic hematopoietic cell transplantation (alloHCT) with reduced intensity conditioning is an appealing option for patients with high risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1-21 of 28 days cycles, with intra-patient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age 54 years) with high risk MM were enrolled at 8 centers between 2009 -2012. The median time from alloHCT to LEN initiation was 96 days (66-171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%).Most common reasons for discontinuation were aGVHD (37%) and disease progression (37%). Cumulative incidence of grades III-IV acute GVHD from time of initiation of Len was 17%. . Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplant related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN post alloHCT is feasible at lower doses, although associated with a 38% incidence of aGVHD. Survival outcomes observed in this high risk MM population warrant further study of this approach.
    01/2014;
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    ABSTRACT: Various translocations and mutations have been identified in myeloma and certain aberrations, such as t(4;14) and del17, are linked with disease prognosis. To investigate mutational prevalence in myeloma and associations between mutations and patient outcomes, we tested a panel of 41 known oncogenes and tumor suppressor genes in tumor samples from 133 relapsed myeloma patients participating in phase 2 or 3 clinical trials of bortezomib. DNA mutations were identified in 14 genes. BRAF as well as RAS genes were mutated in a large proportion of cases (45.9%) and these mutations were mutually exclusive. New recurrent mutations were also identified, including in the PDGFRA and JAK3 genes. NRAS mutations were associated with a significantly lower response rate to single-agent bortezomib (7% versus 53% in patients with mutant versus wild-type NRAS, P = .00116, Bonferroni-corrected P = .016), as well as shorter time-to-progression in bortezomib-treated patients (P = .0058, Bonferroni-corrected P = .012). However, NRAS mutation did not impact outcome in patients treated with high-dose dexamethasone. KRAS mutation did not reduce sensitivity to bortezomib or dexamethasone. These findings identify a significant clinical impact of NRAS mutation in myeloma and demonstrate a clear example of functional differences between the KRAS and NRAS oncogenes.
    Blood 12/2013; · 9.06 Impact Factor
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    ABSTRACT: CD74, expressed in multiple myeloma (MM), was evaluated as a target for immunotherapy with milatuzumab (a humanized anti-CD74 antibody). In a multicentre dose escalation study, 25 patients with advanced MM received milatuzumab doses of 1·5 (N = 8), 4·0 (N = 9), 8·0 (N = 4) or 16·0 mg/kg (N = 4) administered twice weekly x 4. They had a median of 5 prior treatments (17 post ≥1 stem cell transplantation) and were refractory (N = 7) or relapsed (N = 18) with generally short-lived responses to last treatment (median 4·0 months). After increasing prophylactic medications and slowing administration, infusions were well tolerated (National Cancer Institute-Common Terminology Criteria v3 toxicity Grades 1-2) with no dose-limiting toxicity at higher doses. Only one patient developed borderline positive human anti-milatuzumab antibody titres of uncertain clinical significance. Although milatuzumab was rapidly cleared from circulation with little serum accumulation and low trough levels, B-cell levels were moderately decreased with treatment (median decrease, 34%). There were no objective responses by European Group for Blood and Marrow Transplantation criteria, but 5 of 19 patients (26%) who completed treatment in this heavily pretreated and generally refractory group had stable disease for ≥3 months post-treatment (one continuing for 17 months). Disease stabilization and evidence of pharmacodynamic activity support further development for use in combination with other agents or as a drug conjugate. (Clinicaltrials.gov identifier: NCT00421525).
    British Journal of Haematology 09/2013; · 4.94 Impact Factor
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    ABSTRACT: MAGE A3, which belongs to the family of cancer-testis antigens, is an attractive target for adoptive therapy given its reactivation in various tumors and limited expression in normal tissues. We developed an affinity-enhanced T cell receptor (TCR) directed to a human leukocyte antigen (HLA)-A*01-restricted MAGE A3 antigen (EVDPIGHLY) for use in adoptive therapy. Extensive preclinical investigations revealed no off-target antigen recognition concerns; nonetheless, administration to patients of T cells expressing the affinity-enhanced MAGE A3 TCR resulted in a serious adverse event (SAE) and fatal toxicity against cardiac tissue. We present a description of the preclinical in vitro functional analysis of the MAGE A3 TCR, which failed to reveal any evidence of off-target activity, and a full analysis of the post-SAE in vitro investigations, which reveal cross-recognition of an off-target peptide. Using an amino acid scanning approach, a peptide from the muscle protein Titin (ESDPIVAQY) was identified as an alternative target for the MAGE A3 TCR and the most likely cause of in vivo toxicity. These results demonstrate that affinity-enhanced TCRs have considerable effector functions in vivo and highlight the potential safety concerns for TCR-engineered T cells. Strategies such as peptide scanning and the use of more complex cell cultures are recommended in preclinical studies to mitigate the risk of off-target toxicity in future clinical investigations.
    Science translational medicine 08/2013; 5(197):197ra103. · 10.76 Impact Factor
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    ABSTRACT: The efficacy and safety of plerixafor + G-CSF in enhancing hematopoietic stem cell mobilization and collection has been demonstrated in two phase III studies involving patients with NHL or MM. In these pivotal studies, plerixafor + G-CSF significantly increased the proportion of patients achieving target stem cell yields, compared to placebo + G-CSF. In this analysis, we compare the efficacy and safety of plerixafor + G-CSF vs. placebo + G-CSF in patients enrolled in the two phase III studies, stratified by age: ≥60 years of age and <60 years of age. The proportion of older patients who achieved target stem cell yields were significantly higher in the plerixafor group than in placebo group (NHL: 50.9% vs. 25.4%, P<0.001; MM: 69.6% vs. 23.7%, P<0.001). In this older cohort, the median times to neutrophil and to platelet engraftment following autologous stem cell transplant were comparable between the plerixafor and placebo groups. Similar efficacy findings were observed in the younger age group. The most common adverse events (all grades) reported among older patients in the plerixafor group included diarrhea (41.3%), nausea (38.9%), fatigue (30.2%), and injection-site reaction (29.4%). The frequency of adverse events was similar between the older and the younger age groups. Taken together, our subanalysis demonstrate that plerixafor + G-CSF can be safely and effectively used in adult patients of all ages, including those ≥60 years, to support optimal stem cell mobilization for autologous stem cell transplantation.
    American Journal of Hematology 08/2013; · 4.00 Impact Factor
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    ABSTRACT: Salvage chemotherapy followed by autologous stem cell transplant (ASCT) remains the current standard of care for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) with chemosensitive disease. The addition of rituximab results in improved overall survival (OS) after first-line treatment, but cure rates of salvage therapy with ASCT are inferior when compared to historical controls. Historically, patients with DLBCL with disease progression following ASCT have had an extremely poor prognosis with a median OS of 3 months. However, there are little data regarding outcomes in the rituximab era. We performed a retrospective study of 56 patients with relapsed or refractory DLBCL with prior exposure to rituximab who had disease progression following ASCT. The median OS from progression following ASCT for the cohort was 9.9 months (95% CI: 5.3-13.1 months). Patients who progressed less than 1 year from ASCT had a significantly shorter OS than those who progressed at 1 year or greater from ASCT (8.2 vs. 26.7 months, p=0.01). Patients with at least stable disease following ASCT had a longer OS than those who progressed immediately after ASCT (12.3 vs. 5.3 months, p=0.01). Other factors associated with OS were International Prognostic Index (IPI) (p=0.01) and LDH level (p=0.003) at the time of progression following ASCT. In the rituximab era, the prognosis for patients with disease progression following ASCT remains poor, but is improved when compared with historical controls. Ultimately, more work needs to be done to develop novel therapeutic strategies tailored to individual patients in this heterogeneous population.
    American Journal of Hematology 06/2013; · 4.00 Impact Factor
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    ABSTRACT: An obstacle to cancer immunotherapy has been that the affinity of T cell receptors (TCRs) for antigens expressed in tumors is generally low. We initiated clinical testing of engineered T cells expressing an affinity-enhanced T cell receptor against HLA-A*01-restricted MAGE-A3. Open-labeled protocols to test the TCRs for patients with myeloma and melanoma were initiated. The first two treated patients developed cardiogenic shock and died within a few days of T cell infusion, events not predicted by pre-clinical studies of the high-affinity T cell receptors (TCR). Gross findings at autopsy revealed severe myocardial damage and histopathological analysis revealed T cell infiltration. No MAGE-A3 expression was detected in heart autopsy tissues. Robust proliferation of the engineered T cells in vivo was documented in both patients. A beating cardiomyocyte culture generated from induced pluripotent stem cells triggered T cell killing, which was due to recognition of an unrelated peptide derived from the striated muscle specific protein titin. These cases demonstrate that TCR-engineered T cells can have serious and not readily predictable off-target and organ-specific toxicities, and highlight the need for improved methods to define the specificity of engineered TCRs. The protocols were registered at clinicaltrials.gov (NCT01350401 and NCT01352286).
    Blood 06/2013; · 9.06 Impact Factor
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    ABSTRACT: Several cytogenetic abnormalities are associated with poor outcomes in multiple myeloma (MM). We prospectively analyzed the impact of cytogenetic abnormalities on outcomes during the phase 2 PX-171-003-A1 study of single-agent carfilzomib for relapsed and refractory MM. In the response-evaluable population (257/266), fluorescence in situ hybridization (FISH)/conventional cytogenetic profiles were available for 229 patients; 62 (27.1%) had high-risk cytogenetics-del 17p13, t(4;14), or t(14;16) by interphase FISH, or deletion 13 or hypodiploidy by metaphase cytogenetics-and 167 (72.9%) had standard-risk profiles. Generally, baseline characteristics were similar between subgroups, but ISS stage III disease was more common in high- versus standard-risk patients (41.9 vs 27.5%) as was ECOG performance status 1/2 (85.5 vs 68.3%). Overall response was comparable between subgroups (25.8 vs 24.6%, respectively; P=0.85), while time-to-event endpoints showed a trend of shorter duration in high-risk patients, including median duration of response (5.6 months [95% CI 3.7-7.8] vs 8.3 months [95% CI 5.6-12.3]) and overall survival (9.3 [95% CI 6.5-13.0] vs 19.0 months [95% CI 15.4-NE]; P=0.0003). Taken together, these findings demonstrate that single-agent carfilzomib is efficacious and has the potential to at least partially overcome the impact of high-risk cytogenetics in heavily pre-treated patients with MM.Leukemia accepted article preview online, 14 May 2013; doi:10.1038/leu.2013.152.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 05/2013; · 10.16 Impact Factor
  • A L Garfall, D T Vogl, B M Weiss, E A Stadtmauer
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    ABSTRACT: Allogeneic hematopoietic cell transplantation for plasma cell myeloma can lead to graft-vs-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies seek to induce more specific, reliable and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Strategies under development include infusion of vaccine-primed and ex vivo expanded/costimulated autologous T cells after high-dose melphalan, genetic engineering of autologous T cells with receptors for myeloma-specific epitopes, administration of DC/plasma cell fusions and administration expanded marrow-infiltrating lymphocytes. In addition, novel immunomodulatory drugs such as inhibitors of the programmed death-1 T cell regulatory pathway may synergize with cellular immunotherapies.Bone Marrow Transplantation advance online publication, 6 May 2013; doi:10.1038/bmt.2013.54.
    Bone marrow transplantation 05/2013; · 3.00 Impact Factor
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    ABSTRACT: BACKGROUND: Donor leukocyte infusions (DLI) can induce potent graft-versus-leukemia (GvL) activity for patients with relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation (HSCT). Unfortunately, except for chronic phase chronic myelogenous leukemia, responses to DLI have been disappointing. GvL induction is likely to be most effective in the setting of minimal residual disease. Therefore, prevention of relapse by using DLI prophylactically for high-risk patients may improve outcomes of allogeneic HSCT. We have previously reported that ex-vivo co-stimulated T cells infusions (activated DLI, or aDLI) as treatment for relapse are safe and have potent GvL effects. We hypothesized that prophylactic aDLI can be given safely and prevent relapse in high-risk patients after allogeneic HSCT. METHODS: Eighteen patients with AML (14), ALL (3), or MDS (1) received allogeneic SCT after a reduced intensity-conditioning (RIC) regimen with alemtuzumab, fludarabine, and busulfan. Graft-versus-host-disease (GvHD) prophylaxis consisted of tacrolimus and methotrexate with a planned early and rapid taper of tacrolimus. Patients without GvHD, off immune suppression and in remission received aDLI at a dose of 1 x10(7) CD3+ cells/kg (aDLI #1) at D+120, and a second infusion of 1 x 10(8) CD3 cells/kg (aDLI #2) at D+180. RESULTS: At median follow-up of 58 months, 5/18 (28%) patients are alive and 4 remain in remission. Eleven (65%) relapsed at median time of 191 days. Twelve of 18 patients received at least one aDLI. Six of the 12 aDLI#1 patients also received aDLI#2. Six patients did not receive any aDLI due to early relapse (2), protocol ineligibility (1), and GvHD (3). Of the 12 patients who received aDLI#1, only 2/12 developed GVHD. Two out of 12 patients remain in remission. Disease recurrence was the cause of death in 10/13 (77%) patients who died. CONCLUSION: Prophylactic ex-vivo co-stimulated CD3/CD28 DLI is safe, feasible, and not associated with significant GvHD. Relapse remains the major cause of treatment failure after RIC HSCT even with rapid withdrawal of immune suppression and the use of prophylactic aDLI. Better strategies to prevent relapse are needed.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2013; · 3.15 Impact Factor
  • Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2013; · 3.15 Impact Factor
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    ABSTRACT: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation. Although PTLD typically has a B-cell histology, an uncommon variant, plasmacytic PTLD can present as a monoclonal plasma cell proliferation similar to plasmacytomas seen in multiple myeloma. A retrospective analysis was performed on nine patients at our center with plasmacytic PTLD as characterized by plasmacytic histology with the presence of CD138 and lack of CD20. Of the 210 adult solid organ transplant PTLD patients diagnosed between 1988 and 2012, 9 (4%) had a histological appearance consistent with plasmacytic PTLD. The median time from transplant to diagnosis was 3.7 years (range 8 months-24 years). All patients presented with extranodal and often subcutaneous solid tumors. Laboratory features included elevated LDH and beta-2 microglobulin levels, monoclonal gammopathy, and EBV positivity of the tumor. Unlike conventional multiple myeloma, patients had normal calcium levels and only mild anemia. Six patients who have completed treatment achieved complete responses with radiation therapy and/or reduction in immunosuppression with two patients now greater than 5 years in continuous complete response. Plasmacytic PTLD, despite its plasmacytic histology, is responsive to conventional therapies used for B-cell PTLD including reduction in immunosuppression and radiation therapy.
    Transplant International 03/2013; · 3.16 Impact Factor
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    ABSTRACT: PURPOSEThis clinical trial evaluated standard-dose radioimmunotherapy with a chemotherapy-based transplantation regimen followed by autologous hematopoietic cell transplantation versus rituximab with the same regimen in patients with relapsed diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS Patients with chemotherapy-sensitive persistent or relapsed DLBCL were randomly assigned to receive iodine-131 tositumomab (dosimetric dose of 5 mCi on day -19 and therapeutic dose of 0.75 Gy on day -12), carmustine 300 mg/m2 (day -6), etoposide 100 mg/m2 twice daily (days -5 to -2), cytarabine 100 mg/m2 twice daily (days -5 to -2), and melphalan 140 mg/m2 (day -1; B-BEAM) or rituximab 375 mg/m2 on days -19 and -12 and the same chemotherapy regimen (R-BEAM).ResultsTwo hundred twenty-four patients were enrolled, with 113 patients randomly assigned to R-BEAM and 111 patients assigned to B-BEAM. Two-year progression-free survival (PFS) rates, the primary end point, were 48.6% (95% CI, 38.6% to 57.8%) for R-BEAM and 47.9% (95% CI, 38.2% to 57%; P = .94) for B-BEAM, and the 2-year overall survival (OS) rates were 65.6% (95% CI, 55.3% to 74.1%) for R-BEAM and 61% (95% CI, 50.9% to 69.9%; P = .38) for B-BEAM. The 100-day treatment-related mortality rates were 4.1% (95% CI, 0.2% to 8.0%) for R-BEAM and 4.9% (95% CI, 0.8% to 9.0%; P = .97) for B-BEAM. The maximum mucositis score was higher in the B-BEAM arm (0.72) compared with the R-BEAM arm (0.31; P < .001). CONCLUSION The B-BEAM and R-BEAM regimens produced similar 2-year PFS and OS rates for patients with chemotherapy-sensitive relapsed DLBCL. No differences in toxicities other than mucositis were noted.
    Journal of Clinical Oncology 03/2013; · 18.04 Impact Factor
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    ABSTRACT: Although the role of autologous hematopoietic cell transplantation (auto-HCT) is well established in neuroblastoma (NBL), the role of allogeneic HCT (allo-HCT) is controversial. The Center for International Blood and Marrow Transplant Research conducted a retrospective review of 143 allo-HCT for NBL reported in 1990-2007. Patients were categorized into two different groups: those who had not (Group 1) and had (Group 2) undergone a prior auto-HCT (n=46 and 97, respectively). One-year and five-year OS were 59% and 29% for Group 1 and 50% and 7% for Group 2, respectively. Among donor types, disease-free survival (DFS) and OS were significantly lower for unrelated transplants at 1 and 3 years but not at 5 years post HCT. Patients in CR or very good partial response (VGPR) at transplant had lower relapse rates and better DFS and OS, compared with those not in CR or VGPR. Our analysis indicates that allo-HCT can cure some neuroblastoma patients, with lower relapse rates and improved survival in patients without a history of prior auto-HCT as compared with those patients who had previously undergone auto-HCT. Although the data do not address why either strategy was chosen for patients, allo-HCT after a prior auto-HCT appears to offer minimal benefit. Disease recurrence remains the most common cause of treatment failure.Bone Marrow Transplantation advance online publication, 18 February 2013; doi:10.1038/bmt.2012.284.
    Bone marrow transplantation 02/2013; · 3.00 Impact Factor
  • Yvette C Tanhehco, Dan T Vogl, Edward A Stadtmauer, Una O'Doherty
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    ABSTRACT: The introduction of plerixafor as a peripheral blood stem cell mobilization agent has allowed more patients with multiple myeloma, non-Hodgkin's lymphoma, and Hodgkin's disease to mobilize sufficient hematopoietic progenitor cells (HPCs) to proceed to autologous transplantation. Because of the high cost of plerixafor, it is not routinely used in all patients undergoing HPC mobilization. If cost were not an issue, an argument could be made that plerixafor could be added to every mobilization regimen, but cost is an issue so in an attempt to be more cost-effective, many centers have limited plerixafor use to patients who have failed or who are predicted to fail collection of adequate numbers of cells by other methods. Additionally, plerixafor is now under investigation both for HPC collection of healthy donors for allogeneic stem cell transplantation and as an adjunct therapy (i.e., chemosensitizing agent) for acute leukemias. This article briefly reviews the role of plerixafor in autologous and allogeneic transplantation as well as its emerging role in the treatment of acute leukemias. Emphasis is placed on the choice of appropriate patients for plerixafor use to assure an adequate stem cell yield while maximizing the cost effectiveness of using plerixafor. The role of prophylactic collections and future areas of research are also presented.
    Transfusion 01/2013; · 3.53 Impact Factor

Publication Stats

8k Citations
1,395.18 Total Impact Points

Institutions

  • 1992–2014
    • University of Pennsylvania
      • • "Abramson" Cancer Center
      • • Division of Hematology/Oncology
      Philadelphia, Pennsylvania, United States
  • 2013
    • Washington University in St. Louis
      San Luis, Missouri, United States
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
  • 1989–2013
    • Hospital of the University of Pennsylvania
      • • Department of Medicine
      • • Division of Hematology/Oncology
      • • Division of General Medicine
      Philadelphia, Pennsylvania, United States
  • 2012
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
    • Fred Hutchinson Cancer Research Center
      • Division of Clinical Research
      Seattle, WA, United States
  • 2010
    • Loyola University Maryland
      Baltimore, Maryland, United States
    • Loyola University Chicago
      Chicago, Illinois, United States
  • 2009
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2005–2007
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, MA, United States
    • University of Maryland Medical Center
      Baltimore, Maryland, United States
  • 2002
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 2000
    • Tufts University
      Georgia, United States
  • 1997
    • New England Baptist Hospital
      Boston, Massachusetts, United States
  • 1994
    • Group Health Cooperative
      Seattle, Washington, United States