Rainer Storb

Publications (246)1487.41 Total impact

• Article: Impact of acute kidney injury on long-term mortality after nonmyeloablative hematopoietic cell transplantation.

  Chirag R Parikh, Sri G Yarlagadda, Barry Storer, Mohamed Sorror, Rainer Storb, Brenda Sandmaier
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  ABSTRACT: Acute kidney injury (AKI) occurs frequently after nonmyeloablative hematopoietic cell transplantation (HCT). The severity of AKI after nonmyeloablative HCT has association with short-term mortality. However, the long-term effect of AKI on survival after nonmyeloablative HCT is not known. We performed a retrospective analysis of patients who underwent an HLA matched nonmyeloablative HCT between 1997 and 2006. Patients were followed for a median of 36 (range: 3-99) months. AKI occurring up to day 100 was defined as a >2-fold increase in serum creatinine or requirement of dialysis. Of the 358 patients who were included in the analysis, 200 (56%) had AKI, 158 (44%) had no AKI. Overall, 158 patients (43%) died during follow-up. After controlling for potential confounders, the adjusted hazard ratio for overall mortality associated with AKI was 1.57 (95 % confidence interval [CI] 1.2-2.3; P = .0006). The adjusted hazards ratio of nonrelapse mortality (NRM) associated with AKI was 1.72 (95% CI 0.9-3.1; P = .07). AKI is an independent predictor of overall mortality after nonmyeloablative HCT. This finding reiterates the importance of identifying preventative strategies in nonmyeloablative HCT for attenuating incidence and severity of AKI.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2008; 14(3):309-15. · 3.15 Impact Factor
• Article: Comparable outcomes after nonmyeloablative hematopoietic cell transplantation with unrelated and related donors.

  Marco Mielcarek, Barry E Storer, Brenda M Sandmaier, Mohamed L Sorror, David G Maloney, Effie Petersdorf, Paul J Martin, Rainer Storb
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  ABSTRACT: We sought to determine whether patients with hematologic malignancies treated by nonmyeloablative hematopoietic cell transplantation (HCT) at a single institution between December 1997 and June 2006 had worse outcomes with grafts from unrelated donors (URDs) (n = 184) compared with HLA-identical related donors (n = 221). The nonmyeloablative preparative regimen consisted of 2 Gy of total body irradiation (TBI) with (78%) or without (22%) fludarabine, along with posttransplantation mycophenolate mofetil (MMF) and cyclosporine (CSa). After adjusting for the HCT comorbidity index, relapse risk, patient age, stem cell source, preparative regimen, previous cytomegalovirus (CMV) infection, and sex mismatch of donor and recipient in multivariate analysis, we found no statistically significant differences between unrelated and related HCT recipients in terms of risk of nonrelapse mortality (NRM; hazard ratio [HR] = 0.98; 95% confidence interval = 0.6-1.6; P = .94), relapse (HR = 1.04; 95% confidence interval = 0.7-1.5; P = .82), or overall mortality (HR = 0.99; 95% confidence interval = 0.7-1.4; P = .94). Overall rates of severe acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) also were not significantly different between the 2 groups. We conclude that within the limitations of a retrospective study, these results indicate that candidates for nonmyeloablative HCT without suitable related donors may expect similar outcomes with grafts from URDs.
  Biology of Blood and Marrow Transplantation 01/2008; 13(12):1499-507. · 3.87 Impact Factor
• Article: Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences.

  Mohamed L Sorror, Sergio Giralt, Brenda M Sandmaier, Marcos De Lima, Munir Shahjahan, David G Maloney, H Joachim Deeg, Frederick R Appelbaum, Barry Storer, Rainer Storb
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  ABSTRACT: A new hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was effective in predicting outcomes among patients with hematologic malignancies who underwent HCT at Fred Hutchinson Cancer Research Center (FHCRC). Here, we compared the performance of the HCT-CI to 2 other indices and then tested its capacity to predict outcomes among 2 cohorts of patients diagnosed with a single disease entity, acute myeloid leukemia in first complete remission, who underwent transplantation at either FHCRC or M. D. Anderson Cancer Center (MDACC). FHCRC patients less frequently had unfavorable cytogenetics (15% versus 36%) and HCT-CI scores of 3 or more (21% versus 58%) compared with MDACC patients. We found that the HCT-CI had higher sensitivity and outcome predictability compared with the other indices among both cohorts. HCT-CI scores of 0, 1 to 2, and 3 or more predicted comparable nonrelapse mortality (NRM) among FHCRC and MDACC patients. In multivariate models, HCT-CI scores were associated with the highest hazard ratios (HRS) for NRM and survival among each cohort. The 2-year survival rates among FHCRC and MDACC patients were 71% versus 56%, respectively. After adjustment for risk factors, including HCT-CI scores, no difference in survival was detected (HR: 0.98, P = .94). The HCT-CI is a sensitive and informative tool for comparing trial results at different institutions. Inclusion of comorbidity data in HCT trials provides valuable, independent information.
  Blood 01/2008; 110(13):4606-13. · 9.90 Impact Factor
• Article: HLA-matched related donor hematopoietic cell transplantation in 43 patients with Fanconi anemia conditioned with 60 mg/kg of cyclophosphamide.

  Carmem M Bonfim, Carlos R de Medeiros, Marco A Bitencourt, José Zanis-Neto, Vaneuza A M Funke, Daniela C Setubal, Jefferson Ruiz, Jean E Sanders, Mary E D Flowers, Hans-Peter Kiem, Rainer Storb, Ricardo Pasquini
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  ABSTRACT: Cells from Fanconi anemia (FA) patients are hypersensitive to alkylating agents and radiation traditionally used as conditioning regimens for marrow cell transplantation, and patients experience serious toxicities. To reduce toxicities, we used progressively lower doses of cyclophosphamide (CY) for conditioning. Here, we report the results in 43 FA patients who received marrow transplantation from HLA-matched related donors (37 siblings and 6 other relatives). Conditioning consisted of 15 mg CY/kg/day for 4 days along with Mesna. Methotrexate and cyclosporine were given for graft-versus-host disease (GVHD) prophylaxis. Forty patients (93%) are alive with a median follow-up of 3.7 (range 0.6 to 7.9) years. One patient with primary graft failure was successfully retransplanted. Three of 4 patients with late graft failures were retransplanted, and 2 of those are alive; 1 died before a second marrow graft. Twelve patients including 3 with rejection had cytogenetic abnormalities in their marrow cells before transplantation. Acute grade II-III and chronic GVHD (aGVHD, cGVHD) were seen in 17% and 28.5% of patients, respectively. These results confirm and extend our previous observations that conditioning with 60 mg CY/kg allows for sustained engraftment of HLA-matched related marrow grafts in most FA patients and is associated with low toxicity, low incidences of aGVHD and cGVHD, and excellent long-term survival.
  Biology of Blood and Marrow Transplantation 01/2008; 13(12):1455-60. · 3.87 Impact Factor
• Article: Nonmyeloablative allogeneic hematopoietic cell transplantation in relapsed, refractory, and transformed indolent non-Hodgkin's lymphoma.

  Andrew R Rezvani, Barry Storer, Michael Maris, Mohamed L Sorror, Edward Agura, Richard T Maziarz, James C Wade, Thomas Chauncey, Stephen J Forman, Thoralf Lange, Judith Shizuru, Amelia Langston, Michael A Pulsipher, Brenda M Sandmaier, Rainer Storb, David G Maloney
  [show abstract] [hide abstract]
  ABSTRACT: Few effective treatment options exist for chemotherapy-refractory indolent or transformed non-Hodgkin's lymphoma (NHL). We examined the outcome of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in this setting. Sixty-two patients with indolent or transformed NHL were treated with allogeneic HCT from related (n = 34) or unrelated (n = 28) donors after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Nine unrelated donors were mismatched for >/= one HLA antigen. Sixteen patients had histologic transformation before HCT. Twenty patients (32%) had progressive disease after previous high-dose therapy with autologous HCT. Median age was 54 years, and patients had received a median of six lines of treatment before HCT. Median follow-up time after HCT was 36.6 months. At 3 years, the estimated overall survival (OS) and progression-free survival (PFS) rates were 52% and 43%, respectively, for patients with indolent disease, and 18% and 21%, respectively, for patients with transformed disease. Patients with indolent disease and related donors (n = 26) had 3-year estimated OS and PFS rates of 67% and 54%, respectively. The incidences of grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 and 4 acute GVHD, and extensive chronic GVHD were 63%, 18%, and 47%, respectively. Among survivors, the median Karnofsky performance status at last follow-up was 85%. Nonmyeloablative allogeneic HCT can produce durable disease-free survival in patients with relapsed or refractory indolent NHL, even in this relatively elderly and heavily pretreated cohort. Outcomes were particularly good in patients with untransformed disease and related donors, whereas patients with transformed disease did poorly. Long-term survivors reported good overall functional status.
  Journal of Clinical Oncology 01/2008; 26(2):211-7. · 18.37 Impact Factor
• Article: Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia.

  Mohamed L Sorror, Barry E Storer, David G Maloney, Brenda M Sandmaier, Paul J Martin, Rainer Storb
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  ABSTRACT: Allogeneic conventional hematopoietic cell transplantation (HCT) can be curative treatment for lymphoid malignancies, but it has been characterized by high nonrelapse mortality (NRM). Here, we compared outcomes among patients with lymphoma or chronic lymphocytic leukemia given either nonmyeloablative (n = 152) or myeloablative (n = 68) conditioning. Outcomes were stratified by the HCT-specific comorbidity index. Patients in the nonmyeloablative group were older, had more previous treatment and more comorbidities, more frequently had unrelated donors, and more often had malignancy in remission compared with patients in the myeloablative group. Patients with indolent versus aggressive malignancies were equally distributed among both cohorts. After HCT, patients without comorbidities both in the nonmyeloablative and myeloablative cohorts had comparable NRM (P = .74), overall survival (P = .75), and progression-free survival (P = .40). No significant differences were observed (P = .91, P = .89, and P = .40, respectively) after adjustment for pretransplantation variables. Patients with comorbidities experienced lower NRM (P = .009) and better survival (P = .04) after nonmyeloablative conditioning. These differences became more significant (P < .001 and .007, respectively) after adjustment for other variables. Further, nonmyeloablative patients with comorbidities had favorable adjusted progression-free survival (P = .01). Patients without comorbidities could be enrolled in prospective randomized studies comparing different conditioning intensities. Younger patients with comorbidities might benefit from reduced conditioning intensity.
  Blood 01/2008; 111(1):446-52. · 9.90 Impact Factor
• Article: Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

  Christoph Kahl, Barry E Storer, Brenda M Sandmaier, Marco Mielcarek, Michael B Maris, Karl G Blume, Dietger Niederwieser, Thomas R Chauncey, Stephen J Forman, Edward Agura, [......], Benedetto Bruno, Amelia Langston, Michael A Pulsipher, Peter A McSweeney, James C Wade, Elliot Epner, Finn Bo Petersen, Wolfgang A Bethge, David G Maloney, Rainer Storb
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  ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m(2); n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT.
  Blood 11/2007; 110(7):2744-8. · 9.90 Impact Factor
• Chapter: Nonmyeloablative Therapy and Hematopoietic Cell Transplantation for Hematologic Disorders

  Brenda M. Sandmaier, Rainer Storb
  10/2007: pages 1164 - 1176; , ISBN: 9780470987070
• Chapter: Allogeneic Hematopoietic Cell Transplantation for Aplastic Anemia

  George E. Georges, Rainer Storb
  10/2007: pages 979 - 1001; , ISBN: 9780470987070
• Article: Extended mycophenolate mofetil and shortened cyclosporine failed to reduce graft-versus-host disease after unrelated hematopoietic cell transplantation with nonmyeloablative conditioning.

  Frédéric Baron, Brenda M Sandmaier, Barry E Storer, Michael B Maris, Amelia A Langston, Thoralf Lange, Effie Petersdorf, Wolfgang Bethge, Richard T Maziarz, Peter A McSweeney, Michael A Pulsipher, James C Wade, Thomas R Chauncey, Judith A Shizuru, Mohamed L Sorror, Ann E Woolfrey, David G Maloney, Rainer Storb
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  ABSTRACT: We previously reported data from 103 patients with hematologic malignancies (median age 54 years) who received peripheral blood stem cell (PBSC) grafts from HLA-matched unrelated donors after nonmyeloablative conditioning and were given postgrafting immunosuppression consisting of mycophenolate mofetil (MMF; administered from day 0 until day +40 with taper through day +96) and cyclosporine (CSP; given from day -3 to day +100, with taper through day 180) (historical patients). The incidences of grade II-IV acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were 52% and 49%, respectively, and the 1-year probabilities of relapse, nonrelapse mortality (NRM), and progression-free survival (PFS) were 26%, 18%, and 56%, respectively. Here, we treated 71 patients with hematologic malignancies (median age 56 years) with unrelated PBSC grafts and investigated whether postgrafting immunosuppression with an extended course of MMF, given at full dosing until day +150 and then tapered through day +180, and a shortened course of CSP, through day +80, would promote tolerance induction and reduce the incidence of GVHD (current patients). We observed 77% grade II-IV aGVHD and 45% extensive cGVHD (P=.03, and P=.43, respectively, in current compared to historical patients). The 1-year probabilities of relapse, NRM, and PFS were 23%, 29%, and 47%, respectively (P=.89, P=.02, and P=.08 compared to the historical patients). We conclude that postgrafting immunosuppression with extended MMF and shortened CSP failed to decrease the incidence of GVHD among unrelated PBSC recipients given nonmyeloablative conditioning.
  Biology of Blood and Marrow Transplantation 10/2007; 13(9):1041-8. · 3.87 Impact Factor
• Article: Outcomes among patients with recurrent high-risk hematologic malignancies after allogeneic hematopoietic cell transplantation.

  Marco Mielcarek, Barry E Storer, Mary E D Flowers, Rainer Storb, Brenda M Sandmaier, Paul J Martin
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  ABSTRACT: We retrospectively analyzed outcomes among 307 consecutive patients who had recurrent or persistent acute leukemia (n = 244), chronic myelogenous leukemia in blast phase (CML; n = 28), or advanced myelodysplastic syndromes (MDS; n = 35) after allogeneic hematopoietic cell transplantation and who received at least 1 relapse-directed intervention: withdrawal of immunosuppression, chemotherapy, or donor lymphocyte infusion (DLI). Transplants were performed at a single institution between 1995 and 2004, and outcomes were analyzed according to time intervals from transplantation to detection of malignancy: "early," <100 days (n = 111); "intermediate," 100-200 days (n = 73); and "late," >200 days (n = 123). The overall remission rate was 30%. Compared to early recurrence, intermediate recurrence and late recurrence were associated with increasing probabilities of remission (hazard ratios, 1.89 and 2.16; P = .05 and .02) and decreasing risks of overall mortality (hazard ratios, 0.73 and 0.33; P = .05 and <.0001). The 2-year overall survival (OS) estimates for patients with early, intermediate, and late recurrence were 3%, 9%, and 19%, respectively. Remission was associated with a median survival prolongation of 9.5 months. Individual types or combinations of these nonrandomly assigned relapse-directed interventions were not associated with higher or lower probabilities of remission or survival. More effective intervention strategies are needed for treatment of recurrent high-risk hematologic malignancies after hematopoietic cell transplantation. In the absence of innovative clinical trials, patients with early recurrence might wish to forego further interventions in favor of palliative care.
  Biology of Blood and Marrow Transplantation 10/2007; 13(10):1160-8. · 3.87 Impact Factor
• Article: Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation.

  Mohamed L Sorror, Brenda M Sandmaier, Barry E Storer, Michael B Maris, Frédéric Baron, David G Maloney, Bart L Scott, H Joachim Deeg, Frederick R Appelbaum, Rainer Storb
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  ABSTRACT: Retrospective studies have shown similar survival among patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) after nonmyeloablative compared with myeloablative conditioning. Refined risk stratification is required to design prospective trials. We stratified outcomes among patients with AML (n = 391) or MDS (n = 186) who received either nonmyeloablative (n = 125) or myeloablative (n = 452) allogeneic hematopoietic cell transplantation (HCT) based on comorbidities, as assessed by a HCT-specific comorbidity index (HCT-CI), as well as disease status. Patients receiving nonmyeloablative conditioning were older, more frequently pretreated, more often received unrelated grafts, and more often had HCT-CI scores of 3 compared with patients who received myeloablative conditioning. Patients with HCT-CI scores of 0 to 2 and either low or high disease risks had probabilities of overall survival at 2 years of 70% and 57% after nonmyeloablative conditioning compared with 78% and 50% after myeloablative conditioning, respectively. Patients with HCT-CI scores of 3 and either low or high disease risks had probabilities of overall survival of 41% and 29% with nonmyeloablative conditioning compared with 45% and 24% with myeloablative regimens, respectively. After adjusting for pretransplantation differences, stratified outcomes were not significantly different among patients receiving nonmyeloablative compared with myeloablative conditioning, with the exception of lessened nonrelapse mortality (hazard ratio, 0.50; P = .05) in the highest risk group. Patients with low comorbidity scores could be candidates for prospective randomized trials comparing nonmyeloablative and myeloablative conditioning regardless of disease status. Additional data are required for patients with low-risk diseases and high comorbidity scores. Novel antitumor agents combined with nonmyeloablative HCT should be explored among patients with high comorbidity scores and advanced disease.
  Journal of Clinical Oncology 10/2007; 25(27):4246-54. · 18.37 Impact Factor
• Article: Hematopoietic cell transplantation directly into dystrophic muscle fails to reconstitute satellite cells and myofibers.

  Christian S Kuhr, Marilena Lupu, Rainer Storb
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  ABSTRACT: We sought to determine whether wild-type hematopoietic cell transplantation directly into muscle could restore dystrophin expression in a relevant preclinical canine model of Duchenne muscular dystrophy. In recipients rendered tolerant to their dog leukocyte antigen-matched unaffected littermates through hematopoietic stem cell transplantation, intramuscular injection of donor marrow cells produced no evidence of dystrophin expression, and clonal analysis of satellite cells failed to reveal any donor contribution.
  Biology of Blood and Marrow Transplantation 09/2007; 13(8):886-8. · 3.87 Impact Factor
• Article: Long-term tolerance to kidney allografts in a preclinical canine model.

  Christian S Kuhr, Murad Yunusov, George Sale, Carol Loretz, Rainer Storb
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  ABSTRACT: Durable immune tolerance supporting vascularized allotransplantation offers the possibility of extending graft survival and avoiding harmful complications of chronic immunosuppression. Immune tolerance to renal allografts was induced in a preclinical canine model through engraftment of donor hematopoietic cells using a combination of low-dose total body irradiation and a short course of immunosuppression. Subsequently, donor renal allografts were transplanted accompanied by bilateral native nephrectomies. With 5-year follow up, we found normal renal function in all recipients and no histological evidence of acute or chronic rejection. This tolerance does not extend universally to donor skin grafts, however, with two of four animals rejecting delayed donor skin grafts. Hematopoietic chimerism produces durable and robust immune tolerance to kidney allografts, although incomplete tolerance to donor skin grafting.
  Transplantation 09/2007; 84(4):545-7. · 4.00 Impact Factor
• Article: Stable trichimerism after marrow grafting from 2 DLA-identical canine donors and nonmyeloablative conditioning.

  Scott S Graves, William Hogan, Christian S Kuhr, Razvan Diaconescu, Michael A Harkey, George E Georges, George E Sale, Eustacia Zellmer, Szczepan W Baran, Szczepan Baran, Christoph Jochum, Brad Stone, Rainer Storb
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  ABSTRACT: Although hematopoietic cell transplantation (HCT) is generally accomplished using a single donor, multiple donors have been used to enhance the speed of engraftment, particularly in the case of umbilical cord blood grafts. Here we posed the question in the canine HCT model whether stable dual-donor chimerism could be established using 2 DLA-identical donors. We identified 8 DLA-identical littermate triplets in which the marrow recipients received 2 Gy total body irradiation followed by marrow infusions from 2 donors and postgrafting immunosuppression. All 8 dogs showed initial "trichimerism," which was sustained in 5 dogs, while 2 dogs rejected one of the allografts and remained mixed chimeras, and 1 dog rejected both allografts. Immune function in one trichimeric dog, as tested by mixed leukocyte culture response and antibody response to sheep red blood cells, was found to be normal. Five dogs received kidney grafts from one of their respective marrow donors at least 6 months after HCT without immunosuppressive drugs, and grafts in 4 dogs are surviving without rejection. In summary, following nonmyeloablative conditioning, simultaneous administration of marrow grafts from 2 DLA-identical littermates could result in sustained trichimerism, and immunologic tolerance could include a kidney graft from one of the marrow donors.
  Blood 08/2007; 110(1):418-23. · 9.90 Impact Factor
• Article: High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study.

  Richard A Nash, Peter A McSweeney, Leslie J Crofford, Muneer Abidi, Chien-Shing Chen, J David Godwin, Theodore A Gooley, Leona Holmberg, Gretchen Henstorf, C Fred LeMaistre, [......], Bernadette McLaughlin, Jerry A Molitor, J Lee Nelson, Howard Shulman, Rainer Storb, Federico Viganego, Mark H Wener, James R Seibold, Keith M Sullivan, Daniel E Furst
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  ABSTRACT: More effective therapeutic strategies are required for patients with poor-prognosis systemic sclerosis (SSc). A phase 2 single-arm study of high-dose immunosuppressive therapy (HDIT) and autologous CD34-selected hematopoietic cell transplantation (HCT) was conducted in 34 patients with diffuse cutaneous SSc. HDIT included total body irradiation (800 cGy) with lung shielding, cyclophosphamide (120 mg/kg), and equine antithymocyte globulin (90 mg/kg). Neutrophil and platelet counts were recovered by 9 (range, 7 to 13) and 11 (range, 7 to 25) days after HCT, respectively. Seventeen of 27 (63%) evaluable patients who survived at least 1 year after HDIT had sustained responses at a median follow-up of 4 (range, 1 to 8) years. There was a major improvement in skin (modified Rodnan skin score, -22.08; P < .001) and overall function (modified Health Assessment Questionnaire Disability Index, -1.03; P < .001) at final evaluation. Importantly, for the first time, biopsies confirmed a statistically significant decrease of dermal fibrosis compared with baseline (P < .001). Lung, heart, and kidney function, in general, remained clinically stable. There were 12 deaths during the study (transplantation-related, 8; SSc-related, 4). The estimated progression-free survival was 64% at 5 years. Sustained responses including a decrease in dermal fibrosis were observed exceeding those previously reported with other therapies. HDIT and autologous HCT for SSc should be evaluated in a randomized clinical trial.
  Blood 08/2007; 110(4):1388-96. · 9.90 Impact Factor
• Article: Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novo disease and disease following prior therapy or antecedent hematologic disorders.

  Chunkang Chang, Barry E Storer, Bart L Scott, Eileen M Bryant, Howard M Shulman, Mary E Flowers, Brenda M Sandmaier, Robert P Witherspoon, Richard A Nash, Jean E Sanders, Antonio Bedalov, John A Hansen, Bruce E Clurman, Rainer Storb, Frederick R Appelbaum, H Joachim Deeg
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  ABSTRACT: We analyzed outcomes after hematopoietic cell transplantation (HCT) in 257 patients, 3 to 72.7 years old (median, 43 y), with secondary myelodysplastic syndrome (MDS) including those with transformation to acute myeloid leukemia (tAML). Conditioning regimens included high-dose total-body irradiation (TBI)/chemotherapy (n = 83); busulfan (BU)/cyclophosphamide (CY) (BUCY, n = 122; with BU targeting [tBUCY], n = 93); fludarabine (Flu) with tBU (FLUtBU; n = 12); Flu plus 200 cGy TBI (n = 26); and miscellaneous regimens (n = 14). Donors were HLA-identical or partially mismatched family members in 135 and unrelated individuals in 122 patients. Five-year relapse-free survival was highest (43%) and nonrelapse mortality lowest (28%) among tBUCY-conditioned patients. Outcomes were compared with results in 339 patients who received transplants for de novo MDS/tAML, and a multivariate analysis failed to show significant differences in outcome between the 2 cohorts. Relapse probability and relapse-free survival correlated significantly with disease stage (P < .001) and karyotype (P < .001). Relapse incidence was lower (P = .003) and relapse-free survival superior (P = .02) with unrelated donor transplants. The data suggest that overall inferior outcome in patients with secondary MDS/tAML was related to the frequency of high-risk cytogenetics. For both cohorts, transplantation outcomes improved over the time interval studied.
  Blood 08/2007; 110(4):1379-87. · 9.90 Impact Factor
• Article: Sustained AAV-mediated dystrophin expression in a canine model of Duchenne muscular dystrophy with a brief course of immunosuppression.

  Zejing Wang, Christian S Kuhr, James M Allen, Michael Blankinship, Paul Gregorevic, Jeffrey S Chamberlain, Stephen J Tapscott, Rainer Storb
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  ABSTRACT: Adeno-associated virus-based vector (AAV)-mediated gene delivery has been successful in some animal models of human disease such as the mdx mouse model of human Duchenne muscular dystrophy (DMD). However, recent evidence of immune-mediated loss of vector persistence in dogs and humans suggests that immune modulation might be necessary to achieve successful long-term transgene expression in these species. We have previously demonstrated that direct intramuscular injection of AAV2 or AAV6 in wild-type random-bred dogs resulted in a robust immune response to capsid or capsid-associated proteins. We now demonstrate that a brief course of immunosuppression with a combination of anti-thymocyte globulin (ATG), cyclosporine (CSP), and mycophenolate mofetil (MMF) is sufficient to permit long-term and robust expression of a canine micro-dystrophin (c-micro-dys) transgene in the skeletal muscle of a dog model for DMD (canine X-linked muscular dystrophy, or cxmd dog) and that its expression restored localization of components of the dystrophin-associated protein complex at the muscle membrane. This protocol has potential applications to human clinical trials to enhance AAV-mediated therapies.
  Molecular Therapy 07/2007; 15(6):1160-6. · 6.87 Impact Factor
• Article: Intussusception in canine recipients of hematopoietic cell grafts and surgical correction.

  Murad Y Yunusov, Fabio Kerbauy, Kraig Abrams, Eustacia Zellmer, Michele Spector, Christian S Kuhr, Billanna Hwang, Barry Storer, George E Georges, Benjamin J Weigler, Rainer Storb, Richard A Nash
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  ABSTRACT: Intussusception is a common complication after canine hematopoietic cell transplantation (HCT). The present study was undertaken to evaluate predisposing factors of intussusception and to test whether intussusception can be managed surgically during the period immediately after HCT. We determined the incidence of intussusception after HCT was performed in 325 canine recipients (autologous, n = 43; allogeneic, n = 282) during the interval from January 2002 to May 2005. Intussusception was diagnosed in 16 of 325 dogs (4.9%). Intussusception was not significantly associated with the dose of irradiation, source of hematopoietic graft, use of immunosuppressive agents, gender, or age at transplant. A group of 9 of the affected dogs underwent small-bowel resection after diagnosis, and 7 were managed without surgical intervention. Despite complicating factors such as gastrointestinal toxicity and low neutrophil and platelet counts induced by the marrow conditioning regimen and the use of immunosuppressive agents, successful surgical management of intussusception was achieved in 6 of 9 dogs, as compared with successful management of 0 of 7 without surgery. Intussusception did not recur after surgical intervention in any dog. Recent HCT and post-transplant immunosuppressive therapy are not absolute contraindications to surgical intervention for intussusception in canine recipients of HCT.
  Comparative medicine 07/2007; 57(3):287-91. · 1.05 Impact Factor
• Article: Nonmyeloablative unrelated donor hematopoietic cell transplantation to treat patients with poor-risk, relapsed, or refractory multiple myeloma.

  George E Georges, Michael B Maris, David G Maloney, Brenda M Sandmaier, Mohamed L Sorror, Judith A Shizuru, Thoralf Lange, Edward D Agura, Benedetto Bruno, Peter A McSweeney, Michael A Pulsipher, Thomas R Chauncey, Marco Mielcarek, Barry E Storer, Rainer Storb
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  ABSTRACT: The purpose of this study was to determine long-term outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation (HCT) in patients with poor-risk multiple myeloma. A total of 24 patients were enrolled; 17 patients (71%) had chemotherapy-refractory disease, and 14 (58%) experienced disease relapse or progression after previous autologous transplantation. Thirteen patients underwent planned autologous transplantation followed 43-135 days later with unrelated transplantation, whereas 11 proceeded directly to unrelated transplantation. All 24 patients were treated with fludarabine (90 mg/m(2)) and 2 Gy of total body irradiation before HLA-matched unrelated peripheral blood stem cell transplantation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. The median follow-up was 3 years after allografting. One patient experienced nonfatal graft rejection. The incidences of acute grades II and III and chronic graft-versus-host disease were 54%, 13%, and 75%, respectively. The 3-year nonrelapse mortality (NRM) was 21%. Complete responses were observed in 10 patients (42%); partial responses, in 4 (17%). At 3 years, overall survival (OS) and progression-free survival (PFS) rates were 61% and 33%, respectively. Patients receiving tandem autologous-unrelated transplantation had superior OS and PFS (77% and 51%) compared with patients proceeding directly to unrelated donor transplantation (44% and 11%) (PFS P value = .03). In summary, for patients with poor-risk, relapsed, or refractory multiple myeloma, cytoreductive autologous HCT followed by nonmyeloablative conditioning and unrelated HCT is an effective treatment approach, with low NRM, high complete remission rates, and prolonged disease-free survival.
  Biology of Blood and Marrow Transplantation 05/2007; 13(4):423-32. · 3.87 Impact Factor