Thomas R Chauncey

University of Washington Seattle, Seattle, Washington, United States

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Publications (129)932.19 Total impact

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    ABSTRACT: The study is a randomized phase II trial investigating graft-versus-host disease prophylaxis after nonmyeloablative (90 mg/m2 fludarabine and 2 Gy total body irradiation) human leukocyte antigen matched unrelated donor transplantation. Patients were randomized as follows: Arm 1- tacrolimus 180 days and mycophenolate mofetil 95 days (n=69); arm 2-tacrolimus 150 days and mycophenolate mofetil 180 days (n=71); arm 3- tacrolimus 150 days, mycophenolate mofetil 180 days and sirolimus 80 days (n=68). All patients had sustained engraftment. Grade II-IV acute graft-versus-host disease rates in the 3 arms were 64%, 48% and 47% at day 150, respectively (arm 3 vs. 1 (hazard ratio 0.62, P =.04). Owing to the decreased incidence of acute graft-versus-host disease systemic steroid use was lower at day 150 in arm 3 (32% versus 55% in arm 1 and 49% in arm 2; P =.009). The day 150 incidence of cytomegalovirus reactivation was lower in arm 3 (arm 1, 54%; arm 2, 47%; arm 3, 22%; overall P=.002 by hazard ratio analysis). The nonrelapse mortality was comparable in the 3 arms at 2 years (arm 1, 26%; arm 2, 23%; arm 3, 18%). Toxicity rates and other outcome measures were similar between arms. The addition of sirolimus to tacrolimus and mycophenolate mofetil is safe and associated with lower incidence of acute graft-versus-host disease and cytomegalovirus reactivation. The study was registered with (NCT00105001).
    Haematologica 08/2014; DOI:10.3324/haematol.2014.108340 · 5.87 Impact Factor
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    ABSTRACT: Abstract Rituximab-refractory follicular lymphoma (FL) patients have limited options. Before the rituximab era, autologous stem cell transplantation (ASCT) was shown to improve outcomes in chemotherapy-sensitive, relapsed FL, but the impact of rituximab-sensitivity on these results is unknown. We analyzed 194 consecutive relapsed FL patients who underwent ASCT at out center and categorized them as rituximab-sensitive (RS, n=35), rituximab-refractory (RR, n=65), or no rituximab (NoR, n=94) if transplanted before rituximab was used. Progression-free survival at 3 years was 85% in RS and 35% in RR patients (P = .0004). Only rituximab-sensitivity was significant on multivariate analysis with improved OS (HR 0.24, P = .01) and PFS (HR 0.35, P = .006) in RS patients and increased relapse in RR patients (HR 2.11, P = .01). Pre-transplant rituximab-sensitivity is a strong independent predictor of post-transplant outcomes in relapsed FL, though one-third of RR patients achieved a PFS of over 3 years with ASCT.
    Leukemia & lymphoma 04/2014; 56(1). DOI:10.3109/10428194.2014.911866 · 2.61 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2014; 20(2):S66-S67. DOI:10.1016/j.bbmt.2013.12.076 · 3.35 Impact Factor
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    ABSTRACT: Outcomes with autologous hematopoietic cell transplantation (auto HCT) for relapsed/refractory mantle cell lymphoma (MCL) are typically poor. We hypothesized that certain factors could predict which patients experience a favorable outcome with this approach. We thus developed a predictive score from a cohort of 67 such patients using 3 factors independently associated with progression-free survival (PFS): (1) simplified MIPI score prior to auto HCT (HR 2.9, p = 0.002); (2) B symptoms at diagnosis (HR 2.7, p = 0.005); and (3) remission quotient, calculated by dividing the time in months from diagnosis to auto HCT by the number of prior treatments (HR 1.4, p = 0.02). The estimated 5-year PFS for favorable (n = 23) and unfavorable (n = 44) risk patients were 58% (95% CI, 34-75%) and 15% (95% CI, 6-28%), respectively. These factors also independently predicted overall survival. In summary, we have defined 3 simple factors that can identify patients with relapsed/refractory MCL who derive a durable benefit from salvage auto HCT.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2013; DOI:10.1016/j.bbmt.2013.07.005 · 3.35 Impact Factor
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    ABSTRACT: The risk/benefit of adding fludarabine to a 2 Gy total body irradiation nonmyeloablative regimen is unknown. For this reason we conducted a prospective randomized trial comparing 2 Gy TBI alone or in combination with 90mg/m(2) fludarabine (FLU/TBI) before transplantation of peripheral blood stem cells from HLA-matched related donors. Eighty-five patients with hematological malignancies were randomized to be conditioned with TBI alone (n=44) or FLU/TBI (n=41). All patients had initial engraftment. Two graft rejections were observed, both in the TBI group. Infection rates, nonrelapse mortality, and GVHD were similar between groups. Three-year overall survival was lower in the TBI group (54% vs. 65%; hazard ratio (HR) 0.57; p=0.09), with higher incidences of relapse/progression (55% vs. 40%; HR 0.55; p=0.06) and relapse-related mortality (37% vs. 28%; HR 0.53; p=0.09), and a lower progression-free survival (36% vs. 53%; HR 0.56; p=0.05). Median donor T-cell chimerism levels were significantly lower in the TBI group at days 28 (61% vs. 90%; p<0.0001) and 84 (68% vs. 92%; p<0.0001), as was NK-cell chimerism on day 28 (75% vs. 96%, p=0.0005). In conclusion, this randomized trial demonstrates the importance of fludarabine in augmenting the graft-versus-tumor effect by ensuring prompt and durable high level donor engraftment early post-transplant.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2013; DOI:10.1016/j.bbmt.2013.06.002 · 3.35 Impact Factor
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    ABSTRACT: The impact of donor lymphocyte infusion (DLI) initial cell dose on its outcome is known in patient with chronic myeloid leukemia, but limited in patients with other hematological malignancies. In this retrospective study, we evaluated the effect of initial DLI CD3+ cell dose on graft-versus-host disease (GVHD) and overall survival (OS) after DLI given for relapse of any hematological malignancies after allogeneic hematopoietic cell transplantation (HCT) with high or reduced intensity conditioning. The cohort included 225 patients. Initial DLI CD3+ cell dose/kg recipient body weight was ≤1x10(7) (n=84; Group A), >1.0 to <10 x10(7) (n=58; Group B), and ≥ 10x10(7) (n=66; Group C). Cumulative incidence rates of GVHD at 12 months after DLI were 21%, 45% and 55% for Groups A, B, and C, respectively. Multivariate analysis showed that initial DLI CD3+ cell ≥10x10(7) dose/kg is associated with an increased risk of GVHD after DLI (p=0.03). Moreover, initial DLI CD3+ cell dose of 10x10(7) or higher did not decrease the risk of relapse and did not improve OS. Thus, these results support the use of less than 10x10(7) CD3+ cell/kg as the initial cell dose of DLI for treatment of persistent or recurrent hematological malignancy after HCT.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2013; DOI:10.1016/j.bbmt.2013.03.001 · 3.35 Impact Factor
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    ABSTRACT: PURPOSEWe designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the purest assessment of graft-versus-tumor (GVT) effects apart from conditioning and graft-versus-host disease (GVHD) not augmented by regimen-related toxicities. PATIENTS AND METHODS Patients received low-dose total-body irradiation ± fludarabine before HCT from HLA-matched related (n = 611) or unrelated (n = 481) donors, followed by mycophenolate mofetil and a calcineurin inhibitor to aid engraftment and control GVHD. Median patient age was 56 years (range, 7 to 75 years). Forty-five percent of patients had comorbidity scores of ≥ 3. Median follow-up time was 5 years (range, 0.6 to 12.7 years).ResultsDepending on disease risk, comorbidities, and GVHD, lasting remissions were seen in 45% to 75% of patients, and 5-year survival ranged from 25% to 60%. At 5 years, the nonrelapse mortality (NRM) rate was 24%, and the relapse mortality rate was 34.5%. Most NRM was a result of GVHD. The most significant factors associated with GVHD-associated NRM were serious comorbidities and grafts from unrelated donors. Most relapses occurred early while the immune system was compromised. GVT effects were comparable after unrelated and related grafts. Chronic GVHD, but not acute GVHD, further increased GVT effects. The potential benefit associated with chronic GVHD was outweighed by increased NRM. CONCLUSION Allogeneic HCT relying on GVT effects is feasible and results in cures of an appreciable number of malignancies. Improved results could come from methods that control progression of malignancy early after HCT and effectively prevent GVHD.
    Journal of Clinical Oncology 03/2013; DOI:10.1200/JCO.2012.45.0247 · 17.88 Impact Factor
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    ABSTRACT: Allogeneic stem cell transplant for multiple myeloma (MM) is one treatment associated with long-term disease-free survival. The high incidence of treatment-related mortality and relapses, however, are important reasons for controversy about the role of allografting in the management of MM. We reviewed our results of allografting for MM spanning a period of 34 years in order to better define long-term outcomes and identify areas of progress as well as areas requiring improvement. A total of 278 patients received allogeneic marrow or PBSCs after high-dose myeloablative (N=144) or reduced intensity, non-myeloablative (N=134) regimens. In multivariable analysis, adjusting for differences in patient groups, reduced intensity/non-myeloablative transplants were associated with significantly less acute GVHD, lower transplant mortality, better PFS and overall survival. There were no significant differences in relapse, progression or chronic GVHD, when adjusted. In multivariable analysis of patients receiving only non-myeloablative transplants, decreased overall survival and PFS were associated with relapse after a prior autograft and a β2 microglobulin >4.0. Transplant mortality was reduced and only influenced by a prior tandem autograft.
    Bone marrow transplantation 02/2012; 47(10):1312-7. DOI:10.1038/bmt.2012.1 · 3.47 Impact Factor
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    ABSTRACT: Between 1996 and 1999, 172 patients (median age, 42 years) with hematologic malignancies were randomly assigned to receive either HLA-identical related bone marrow or G-CSF-mobilized peripheral blood mononuclear cells (G-PBMCs) after myeloablative conditioning. Early results showed that transplantation of G-PBMCs, compared with marrow, was associated with significantly superior 2-year disease-free survival (DFS) and overall survival. Ten-year follow-up showed a sustained DFS benefit associated with G-PBMCs (mortality or relapse hazard ratio, 0.64; 95% confidence interval, 0.4-1.0; P = .03), although the likelihood of overall survival was not significantly different between the 2 groups (mortality hazard ratio, 0.75; 95% confidence interval, 0.5-1.2; P = .20). The 10-year cumulative incidence of chronic GVHD and the duration of systemic immunosuppression were similar in the 2 groups. In summary, transplantation of HLA-identical related G-PBMCs, compared with marrow, was associated with superior short-term and long-term DFS, and there was no evidence that this benefit was outweighed by GVHD-related late mortality.
    Blood 02/2012; 119(11):2675-8. DOI:10.1182/blood-2011-12-396275 · 9.78 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2012; 18(2):S214. DOI:10.1016/j.bbmt.2011.12.033 · 3.35 Impact Factor
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    ABSTRACT: Studies by the International Working Group showed that the prognosis of myelofibrosis patients is predicted by the Dynamic International Prognostic Scoring System (DIPSS) risk categorization, which includes patient age, constitutional symptoms, hemoglobin, leukocyte count, and circulating blasts. We evaluated the prognostic usefulness of the DIPSS in 170 patients with myelofibrosis, 12 to 78 years of age (median, 51.5 years of age), who received hematopoietic cell transplantation (HCT) between 1990 and 2009 from related (n = 86) or unrelated donors (n = 84). By DIPSS, 21 patients had low-risk disease, 48 had intermediate-1, 50 had intermediate-2, and 51 had high-risk disease. Five-year incidence of relapse, relapse-free survival, overall survival, and nonrelapse mortality for all patients were 10%, 57%, 57%, and 34%, respectively. Among patients with DIPSS high-risk disease, the hazard ratio for post-HCT mortality was 4.11 (95% CI, 1.44-11.78; P = .008), and for nonrelapse mortality was 3.41 (95% CI, 1.15-10.09; P = .03) compared with low-risk patients. After a median follow-up of 5.9 years, the median survivals have not been reached for DIPSS risk groups low and intermediate-1, and were 7 and 2.5 years for intermediate-2 and high-risk patients, respectively. Thus, HCT was curative for a large proportion of patients with myelofibrosis, and post-HCT success was dependent on pre-HCT DIPSS classification.
    Blood 01/2012; 119(11):2657-64. DOI:10.1182/blood-2011-08-372904 · 9.78 Impact Factor
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    ABSTRACT: A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions. To describe outcomes of patients 60 years or older after receiving minimally toxic nonmyeloablative allogeneic HCT. From 1998 to 2008, 372 patients aged 60 to 75 years were enrolled in prospective clinical HCT trials at 18 collaborating institutions using conditioning with low-dose total body irradiation alone or combined with fludarabine, 90 mg/m(2), before related (n = 184) or unrelated (n = 188) donor transplants. Postgrafting immunosuppression included mycophenolate mofetil and a calcineurin inhibitor. Overall and progression-free survival were estimated by Kaplan-Meier method. Cumulative incidence estimates were calculated for acute and chronic graft-vs-host disease, toxicities, achievement of full donor chimerism, complete remission, relapse, and nonrelapse mortality. Hazard ratios (HRs) were estimated from Cox regression models. Overall, 5-year cumulative incidences of nonrelapse mortality and relapse were 27% (95% CI, 22%-32%) and 41% (95% CI, 36%-46%), respectively, leading to 5-year overall and progression-free survival of 35% (95% CI, 30%-40%) and 32% (95% CI, 27%-37%), respectively. These outcomes were not statistically significantly different when stratified by age groups. Furthermore, increasing age was not associated with increases in acute or chronic graft-vs-host disease or organ toxicities. In multivariate models, HCT-specific comorbidity index scores of 1 to 2 (HR, 1.58 [95% CI, 1.08-2.31]) and 3 or greater (HR, 1.97 [95% CI, 1.38-2.80]) were associated with worse survival compared with an HCT-specific comorbidity index score of 0 (P = .003 overall). Similarly, standard relapse risk (HR, 1.67 [95% CI, 1.10-2.54]) and high relapse risk (HR, 2.22 [95% CI, 1.43-3.43]) were associated with worse survival compared with low relapse risk (P < .001 overall). Among patients aged 60 to 75 years treated with nonmyeloablative allogeneic HCT, 5-year overall and progression-free survivals were 35% and 32%, respectively.
    JAMA The Journal of the American Medical Association 11/2011; 306(17):1874-83. DOI:10.1001/jama.2011.1558 · 30.39 Impact Factor
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    ABSTRACT: High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) are frequently used in an attempt to improve outcome in patients with mantle-cell lymphoma (MCL); however, the importance of intensive induction regimens before transplantation is unknown. To address this question, we evaluated baseline characteristics, time to treatment, induction regimen, disease status at the time of transplantation, and MIPI score at diagnosis and their associations with survival in 118 consecutive patients with MCL who received HDT and ASCT at our centers. The MIPI was independently associated with survival after transplantation in all 118 patients (hazard ratio [HR], 3.5; P < .001) and in the 85 patients who underwent ASCT as initial consolidation (HR, 7.2; P < .001). Overall survival rates were 93%, 60%, and 32% at 2.5 years from ASCT for all patients with low-, intermediate-, and high-risk MIPI, respectively. Low-risk MIPI scores were more common in the intensive induction group than the standard induction group in all patients (64% v 46%, respectively; P = .03) and in the initial consolidation group (66% v 45%, respectively; P = .03). After adjustment for the MIPI, an intensive induction regimen was not associated with improved survival after transplantation in all patients (HR, 0.5; P = .10), the initial consolidation group (HR, 1.1; P = .86), or patients ≤ 60 years old (HR, 0.6; P = .50). Observation of more than 3 months before initiating therapy did not yield inferior survival (HR, 2.1; P = .12) after adjustment for the MIPI in patients receiving ASCT. An intensive induction regimen before HDT and ASCT was not associated with improved survival after adjusting for differences in MIPI scores at diagnosis.
    Journal of Clinical Oncology 08/2011; 29(22):3023-9. DOI:10.1200/JCO.2010.33.7055 · 17.88 Impact Factor
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    ABSTRACT: Cryopreserved peripheral blood stem cell (PBSC) products can induce a number of infusion-related adverse reactions, including life-threatening cardiac, neurologic, and other end-organ complications. Preliminary analyses suggested limiting the daily total nucleated cell dose infused might decrease the incidence of these adverse effects. A policy change implemented in December 2007, limiting the total nucleated cell (TNC) dose to <1.63 × 10(9) TNC/kg/day, allowed us to assess the impact of this intervention on infusion-related safety, infusion schedules, engraftment, and costs in cohorts of patients undergoing autologous stem cell transplants (ASCTs) 2 years before (325 ASCTs in 288 patients) and 2 years after the policy change (519 ASCTs in 479 patients). The percentage of autologous transplant patients requiring multiple day infusions increased from 6% to 24%. Concurrently, the incidence of infusion-related grade 3-5 severe infusion-related adverse events (SAEs) decreased significantly, from 4% (13 of 325) prepolicy change to 0.6% (3 of 519) postpolicy change (P < .0004). Multiday infusions were not associated with increased time to neutrophil or platelet engraftment or the costs of transplantation. We conclude that limiting the daily TNC dose improved the safety of this procedure without compromising engraftment or increasing the costs of the procedure.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2011; 18(2):220-8. DOI:10.1016/j.bbmt.2011.06.003 · 3.35 Impact Factor
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    ABSTRACT: Peripheral blood stem cell (PBSC) products contain more T cells and monocytes when compared with bone marrow (BM), leading to fewer bacterial and fungal infections. Cytomegelovirus (CMV) viral load and disease as well as CMV-specific immune reconstitution were compared in patients enrolled in a randomized trial comparing PSBC and BM transplantation. There was a higher rate of CMV infection and disease during the first 100 days after transplantation among PBSC recipients (any antigenemia/DNAemia: PBSC, 63% vs BM, 42%, P = .04; CMV disease: PBSC, 17% vs BM, 4%, P = .03). By 2 years, CMV disease rates were similar. The early increase in CMV events correlated temporarily with lower CMV-specific CD4(+) T helper and CD8(+) cytotoxic T lymphocyte function at 30 days after transplantation in PBSC recipients. By 3 months after transplantation and thereafter, CMV-specific immune responses were similar between BM and PBSC recipients. In conclusion, higher CMV infection and disease rates occurred in PBSC transplant recipients early after transplantation. These differences may be because of a transient delay in CMV-specific immune reconstitution following PBSC transplantation.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2011; 18(1):66-75. DOI:10.1016/j.bbmt.2011.05.010 · 3.35 Impact Factor
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    ABSTRACT: Allogeneic hematopoietic cell transplantation is a potentially curative treatment for patients with acute lymphoblastic leukemia. However, the majority of older adults with acute lymphoblastic leukemia are not candidates for myeloablative conditioning regimens. A non-myeloablative preparative regimen is a reasonable treatment option for this group. We sought to determine the outcome of non-myeloablative conditioning and allogeneic transplantation in patients with high-risk acute lymphoblastic leukemia. Fifty-one patients (median age 56 years) underwent allogeneic hematopoietic cell transplantation from sibling or unrelated donors after fludarabine and 2 Gray total body irradiation. Twenty-five patients had Philadelphia chromosome-positive acute lymphoblastic leukemia. Eighteen of these patients received post-grafting imatinib. With a median follow-up of 43 months, the 3-year overall survival was 34%. The 3-year relapse/progression and non-relapse mortality rates were 40% and 28%, respectively. The cumulative incidences of grades II and III-IV acute graft-versus-host disease were 53% and 6%, respectively. The cumulative incidence of chronic graft-versus-host disease was 44%. Hematopoietic cell transplantation in first complete remission and post-grafting imatinib were associated with improved survival (P=0.005 and P=0.03, respectively). Three-year overall survival rates for patients with Philadelphia-negative acute lymphoblastic leukemia in first remission and beyond first remission were 52% and 8%, respectively. For patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in first remission who received post-grafting imatinib, the 3-year overall survival rate was 62%; for the subgroup without evidence of minimal residual disease at transplantation, the overall survival was 73%. For patients with high-risk acute lymphoblastic leukemia in first complete remission, non-myeloablative conditioning and allogeneic hematopoietic cell transplantation, with post-grafting imatinib for Philadelphia chromosome-positive disease, can result in favorable long-term survival.
    Haematologica 04/2011; 96(8):1113-20. DOI:10.3324/haematol.2011.040261 · 5.87 Impact Factor
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    ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning regimens imposes prohibitively high risks of morbidity and mortality for patients with high-risk acute myeloid leukemia (AML) who are older or have comorbid conditions. Here, we examined outcomes after nonmyeloablative allogeneic HCT in such patients. Two hundred seventy-four patients (median age, 60 years) with de novo or secondary AML underwent allogeneic HCT from related (n = 118) or unrelated donors (n = 156) after conditioning with 2 Gy of total-body irradiation (TBI) with or without fludarabine. A calcineurin inhibitor and mycophenolate mofetil were used for postgrafting immunosuppression. With a median follow-up of 38 months in surviving patients, the estimated overall survival at 5 years was 33%. The estimated 5-year relapse/progression and nonrelapse mortality rates were 42% and 26%, respectively. The cumulative incidences of grades 2, 3, and 4 acute graft-versus-host disease (GVHD) were 38%, 9%, and 5%, respectively. The cumulative incidence of chronic GVHD at 5 years was 44%. Patients in first and second complete remission had better survival rates than patients with more advanced disease (37% and 34% v 18%, respectively). Patients with HLA-matched related or unrelated donors had similar survivals. Unfavorable cytogenetic risk status was associated with increased relapse and subsequent mortality. Chronic GVHD was associated with lower relapse risk. Allogeneic HCT from related or unrelated donors after conditioning with low-dose TBI and fludarabine, relying almost exclusively on graft-versus-leukemia effects, can result in long-term remissions in older or medically infirm patients with AML.
    Journal of Clinical Oncology 06/2010; 28(17):2859-67. DOI:10.1200/JCO.2009.27.1460 · 17.88 Impact Factor
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    ABSTRACT: HLA-mismatched grafts are a viable alternative source for patients without HLA-matched donors receiving ablative hematopoietic cell transplantation (HCT), although their use in reduced intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT has been not well established. Here, we extended HCT to recipients of HLA class I-mismatched grafts to investigate whether NMA conditioning can establish stable donor engraftment. Fifty-nine patients were conditioned with fludarabine (Flu) 90 mg/m(2) and 2 Gy total body irradiation (TBI), followed by immunosuppression with cyclosporine (CsA) 5.0 mg/kg twice a day and mycophenolate mofetil (MMF) 15 mg/kg 3 times a day for transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSCs) from related (n = 5) or unrelated donors (n = 54) with 1 antigen +/- 1 allele HLA class I mismatch or 2 HLA class I allele mismatches. Sustained donor engraftment was observed in 95% of the evaluable patients. The incidence of grade II-IV acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) was 69% and 41%, respectively. The cumulative probability of nonrelapse mortality (NRM) was 47% at 2 years. Two-year overall and progression-free survival (OS, PFS) was 29% and 28%, respectively. NMA conditioning with Flu and low-dose TBI, followed by HCT using HLA class I-mismatched donors leads to successful engraftment and long-term survival; however, the high incidence of aGVHD and NRM needs to be addressed by alternate GVHD prophylaxis regimens.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2009; 16(3):384-94. DOI:10.1016/j.bbmt.2009.11.004 · 3.35 Impact Factor
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    ABSTRACT: Attempts to overcome multi-drug resistance in acute myeloid leukaemia (AML) have been limited by toxicities. To investigate the effect of reducing peak drug levels, we performed sequential phase II studies using continuous infusion daunorubicin and cytarabine without (AD) and then with ciclosporin (ADC) in older patients with AML. Untreated patients (age 56+ years) received daunorubicin (45 mg/m2 per day for 3 d) and cytarabine (200 mg/m2 per day for 7 d), both by continuous infusion, without (S0112, 60 patients) and then with (S0301, 50 patients) the addition of ciclosporin. Complete response (CR) rates were 38% on S0112 and 44% on S0301. Fatal induction toxicities occurred in 17% and 12% respectively, arising primarily from infection and haemorrhage. Median overall and relapse-free survival was 7 and 8 months for AD respectively, and 6 and 14 months for ADC. Patients with phenotypic or functional P-glycoprotein had somewhat higher CR rates with ADC than AD, although confidence intervals overlapped. In these sequential trials, continuous infusion AD produced CR rates comparable to those with bolus daunorubicin. The addition of ciclosporin did not cause undue toxicities, produced a similar CR rate, and possibly improved relapse-free survival. Further correlate analyses did not identify a subpopulation specifically benefitting from the addition of ciclosporin.
    British Journal of Haematology 10/2009; 148(1):48-58. DOI:10.1111/j.1365-2141.2009.07919.x · 4.96 Impact Factor
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    ABSTRACT: We investigated the impacts of the tempo of early (days 14, 28, and 42) donor T cell and natural killer (NK) cell engraftment, missing recipient killer cell immunoglobulin-like receptor (KIR) ligands, and numbers of donor inhibitory and activating KIR genes on hematopoietic cell transplantation (HCT) outcomes in 282 patients with hematologic malignancies given nonmyeloablative conditioning. Modeling chimerism levels as a continuous linear variable, we found that high early donor T cell chimerism was significantly associated with acute graft-versus-host disease (aGVHD) (P = .01), whereas high donor NK cell chimerism levels had no such association (P = .38). Conversely, high donor NK cell chimerism levels were significantly associated with low relapse risk (P = .0009), whereas no significant association was seen with high donor T cell chimerism (P = .10). The qualitative associations between donor T cell and NK cell chimerism levels and GVHD and relapse did not change after adjustment for the presence of recipient KIR ligands or numbers of donor inhibitory or activating KIR genes. Our data indicate that prompt engraftment of donor NK cells correlated with lessened risks of relapse, but not with GVHD, whereas the converse was true for T cells.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2009; 15(5):580-8. DOI:10.1016/j.bbmt.2009.01.018 · 3.35 Impact Factor

Publication Stats

8k Citations
932.19 Total Impact Points


  • 2001–2014
    • University of Washington Seattle
      • • Department of Medicine
      • • Department of Urology
      Seattle, Washington, United States
    • VA Puget Sound Health Care System
      Washington, Washington, D.C., United States
    • University of Texas Health Science Center at San Antonio
      • Division of Hospital Medicine
      San Antonio, Texas, United States
  • 1995–2013
    • Fred Hutchinson Cancer Research Center
      • Division of Clinical Research
      Seattle, Washington, United States
  • 2003–2010
    • Baylor University
      Waco, Texas, United States
    • Stanford University
      Palo Alto, California, United States
  • 2006
    • University of Utah
      • School of Medicine
      Salt Lake City, Utah, United States
    • University of Leipzig
      Leipzig, Saxony, Germany
  • 2002
    • University of Colorado
      Denver, Colorado, United States
    • Puget Sound Blood Center
      Seattle, Washington, United States