-
Rainer Storb,
Boglarka Gyurkocza,
Barry E Storer,
Mohamed L Sorror,
Karl Blume,
Dietger Niederwieser,
Thomas R Chauncey,
Michael A Pulsipher,
Finn B Petersen,
Firoozeh Sahebi, [......],
Andrew M Yeager,
Kai Hübel,
H Joachim Deeg,
George E Georges,
Mary E D Flowers,
Paul J Martin,
Marco Mielcarek, Ann E Woolfrey,
David G Maloney,
Brenda M Sandmaier
[show abstract]
[hide abstract]
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; · 18.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Purpose: To assess the risk factors for intensive care unit admission among children receiving hematopoietic stem cell transplantation (HSCT) and to test the hypothesis that multiple organ failure (MOF) increases the odds of death among HSCT patients who receive mechanical ventilation (MV). Methods: The chart of all consecutive HSCTs at Seattle Children's Hospital and pediatric HSCT patients admitted to the pediatric critical care unit of a tertiary care pediatric hospital from January 2000 to September 2006 were reviewed retrospectively. Results: Charts of 266 HSCT patients were reviewed. Nonmalignant disease compared to hematologic malignancy, acute graft versus host disease grades III and IV, and second transplant increased the odds of pediatric intensive care unit admission. Among patients receiving MV for >24 hours, 9 (25%) survived for 6 months, while 8 patients (22%) were long-term survivors with a median follow-up time of 3.6 years, a significant improvement compared to a long-term survival of 7% (odds ratio 0.25, 95% confidence intervals: 0.09-0.72, P = .01) reported in a previously published cohort of pediatric HSCT patients at the same institution from 1983 to 1996. Cardiovascular failure, duration of MV for greater than 1 week, and prolonged receipt of continuous renal replacement therapy (CRRT) increased the risk of mortality. Conclusions: Six-month survival of pediatric HSCT patients was 25% and the odds of death were increased by cardiovascular failure but not by MOF. Receipt of mechanical support (ventilation, CRRT) or cardiovascular support (inotropic agents) decreased the likelihood of long-term survival.
Journal of Intensive Care Medicine 08/2012;
-
[show abstract]
[hide abstract]
ABSTRACT: Selection of a suitable graft for allogeneic hematopoietic stem cell transplantation involves consideration of both donor and recipient characteristics. Of primary importance is sufficient donor-recipient HLA matching to ensure engraftment and acceptable rates of GVHD. In this Perspective, the National Marrow Donor Program and the Center for International Blood and Marrow Transplant Research provide guidelines, based on large studies correlating graft characteristics with clinical transplantation outcomes, on appropriate typing strategies and matching criteria for unrelated adult donor and cord blood graft selection.
Blood 05/2012; 120(2):259-65. · 9.90 Impact Factor
-
Lauri M Burroughs, Ann E Woolfrey,
Barry E Storer,
H Joachim Deeg,
Mary E D Flowers,
Paul J Martin,
Paul A Carpenter,
Kris Doney,
Frederick R Appelbaum,
Jean E Sanders,
Rainer Storb
[show abstract]
[hide abstract]
ABSTRACT: Allogeneic marrow transplantation offers curative therapy for children with severe aplastic anaemia (SAA). We report the outcomes of 148 children with SAA who received human leucocyte antigen (HLA)-matched related marrow grafts between 1971 and 2010. Patients were divided into three groups, reflecting changes in conditioning and graft-versus-host disease (GVHD) prophylaxis regimens that occurred over time. Patients in Group 1 were conditioned with cyclophosphamide (CY; 200 mg/kg) followed by 'long' (102 d) methotrexate (MTX). Patients in Groups 2 and 3 received CY alone (Group 2) or combined with anti-thymocyte globulin (Group 3) followed by 'short' (days 1, 3, 6, and 11) MTX and ciclosporin (until day 180). With a median follow-up of 25 years, the 5-year survivals were 66%, 95%, and 100% for Groups 1, 2, and 3, respectively (overall P < 0·0001). The 3-year estimates of graft rejection were 22%, 32%, and 7%, respectively. The probabilities of grades III-IV acute and 2-year chronic GVHD were 15%, 0%, and 3%, and 21%, 21%, and 10%, respectively. Advances in preparative and GVHD prophylaxis regimens, and supportive care during the past 40 years have led to improved outcomes for children with SAA. These results confirm the use of allogeneic marrow transplantation for children with SAA who have HLA-matched related donors.
British Journal of Haematology 04/2012; 158(1):120-8. · 4.94 Impact Factor
-
George E. Georges,
Michael Maris,
Brenda M. Sandmaier,
David G. Maloney,
LyleFeinstein,
Dietger Niederweiser,
Judith A. Shizuru,
Peter A. McSweeney,
Thomas R. Chauncey,
Edward Agura,
Marie-Trse Little,
Firoozeh Sahebi,
Ute Hegenbart,
Michael A. Pulsipher,
Benedetto Bruno,
Stephen Forman, Ann E. Woolfrey,
Jerald P. Radich,
Karl G. Blume,
Rainer Storb
[show abstract]
[hide abstract]
ABSTRACT: Patients with advanced hematological malignancies ineligible for conventional myeloablative allogeneic hematopoietic stem
cell transplantation (HSCT) due to advanced age or medical contraindications were enrolled in a multi-center study to investigate
the safety and efficacy of nonmyeloablative HSCT using a 2 Gy total body irradiation (TBI)-based regimen. A total of 192 patients
(median age 55) were treated with HLA-matched sibling peripheral blood stem cell (PBSC) grafts, and 63 patients (median age
53) received a 10 of 10 HLA-antigen matched unrelated donor (URD) HSCT (PBSC graft, n=48; marrow graft, n=15). Diagnoses included
multiple myeloma (n=61), myelodysplastic syndrome (n=55), chronic myeloid leukemia (n=31), non-Hodgkin lymphoma (n=31), acute
myeloid leukemia (n=28), chronic lymphocytic leukemia (n=24), Hodgkin Disease (n=14). The conditioning regimen was fludarabine
30 mg/m2/d × 3 days and 2 Gy TBI. Ninety-five related HSCT patients received 2 Gy TBI without fludarabine. Postgrafting immunosuppression
was combined mycophenolate mofetil and cyclosporine. Transplants were well tolerated with a median of 0 days of hospitalization
in the first 60 days for eligible patients. For related HSCT recipients, median follow-up was 289 (100–1188) days. Nonfatal
graft rejection occurred in 6.8%. Of those with sustained engraftment, graft-versus-host disease (GVHD) occurred in 49% (33%
grade II, 11% grade III, 5% grade IV). Day-100 non-relapse mortality was 6%. Overall, 59% (114/192) of patients were alive.
The relapse/disease progression mortality was 18%, and non-relapse mortality was 22%. The projected 2-year survival and progression-free
survival were 50% and 40%. For the URD HSCT recipients, median follow-up was 190 (100–468) days. Graft rejection occurred
in 27% (17/63) of patients, mostly in recipients of marrow grafts (9/15). Acute GVHD occurred in 63% (50% grade II, 13% grade
III) of 46 engrafted patients. Chronic GVHD requiring therapy occurred in 50% of patients. Of the 63 URD HSCT patients, 54%
were alive, 37% in CR, 3% PR, and 14% with disease progression or relapse. Related and unrelated nonmyeloablative HSCT is
feasible and potentially curative in patients with advanced hematological malignancies who have no other treatment options.
International Journal of Hematology 04/2012; 76:184-189. · 1.27 Impact Factor
-
Karen K Ballen, Ann E Woolfrey,
Xiaochun Zhu,
Kwang Woo Ahn,
Baldeep Wirk,
Mukta Arora,
Biju George,
Bipin N Savani,
Brian Bolwell,
David L Porter, [......],
Mahmoud D Aljurf,
Matthew H Carabasi,
Mehdi Hamadani,
Philip McCarthy,
Steven Pavletic,
Vikas Gupta,
H Joachim Deeg,
Richard T Maziarz,
Mary M Horowitz,
Wael Saber
[show abstract]
[hide abstract]
ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT) is curative for selected patients with advanced essential thrombocythemia (ET) or polycythemia vera (PV). From 1990 to 2007, 75 patients with ET (median age 49 years) and 42 patients with PV (median age 53 years) underwent transplantations at the Fred Hutchinson Cancer Research Center (FHCRC; n = 43) or at other Center for International Blood and Marrow Transplant Research (CIBMTR) centers (n = 74). Thirty-eight percent of the patients had splenomegaly and 28% had a prior splenectomy. Most patients (69% for ET and 67% for PV) received a myeloablative (MA) conditioning regimen. Cumulative incidence of neutrophil engraftment at 28 days was 88% for ET patients and 90% for PV patients. Acute graft-versus-host disease (aGVHD) grades II to IV occurred in 57% and 50% of ET and PV patients, respectively. The 1-year treatment-related mortality (TRM) was 27% for ET and 22% for PV. The 5-year cumulative incidence of relapse was 13% for ET and 30% for PV. Five-year survival/progression-free survival (PFS) was 55%/47% and 71%/48% for ET and PV, respectively. Patients without splenomegaly had faster neutrophil and platelet engraftment, but there were no differences in TRM, survival, or PFS. Presence of myelofibrosis (MF) did not affect engraftment or TRM. Over 45% of the patients who undergo transplantations for ET and PV experience long-term PFS.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2012; 18(9):1446-54. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Aplastic anemia (AA), a potentially fatal disease, may be cured with marrow transplantation. Survival in pediatric patients has been excellent early after transplantation, but only limited data are available regarding late effects. This study evaluates late effects among 152 patients followed 1-38 years (median, 21.8 years). Transplantation-preparative regimes were mostly cyclophosphamide with or without antithymocyte globulin. Survival at 30 years for the acquired AA patients is 82%, and for the Fanconi anemia patients it is 58% (P = .01). Multivariate analysis demonstrated that chronic GVHD (P = .02) and Fanconi anemia (P = .03) negatively impacted survival. Two Fanconi patients and 18 acquired AA patients developed a malignancy that was fatal for 4. There was an increased incidence of thyroid function test abnormalities among those who received total body irradiation. Cyclophosphamide recipients demonstrated normal growth, basically normal development, and pregnancies with mostly normal offspring. Quality-of-life studies in adult survivors of this pediatric transplantation cohort indicated that patients were comparable with control patients except for difficulty with health and life insurance. These data indicate that the majority of long-term survivors after transplantation for AA during childhood can have a normal productive life.
Blood 06/2011; 118(5):1421-8. · 9.90 Impact Factor
-
Eneida R Nemecek,
Kristin Ellis,
Wensheng He,
Nancy J Bunin,
Rajinder S Bajwa,
Alexandra Cheerva,
Mitchell S Cairo,
Christopher Dvorak,
Michel Duval,
Stella Davies,
Mary Eapen,
Thomas G Gross,
Ayad A Hussein,
Margaret L MacMillan,
Parinda A Mehta,
Michael A Pulsipher,
Adriana Seber, Ann E Woolfrey,
Haydar A Frangoul,
Paul A Carpenter
[show abstract]
[hide abstract]
ABSTRACT: We conducted a retrospective study of 155 children who underwent unrelated donor hematopoietic cell transplantation (HCT) between 1990 and 2005 for acute lymphoblastic leukemia in third remission. The median patient age was 11 years, the median time from diagnosis to first relapse was 36 months, and the median time from first relapse to second relapse was 26 months. Stem cell sources were bone marrow (n = 115), peripheral blood (n = 11), and cord blood (n = 29). All patients received a myeloablative pretransplantation conditioning regimen. The 5-year estimates of leukemia-free survival, relapse, and nonrelapse mortality were 30%, 25%, and 45%, respectively. In multivariate analysis, the only risk factor associated with relapse was the interval between the first relapse and the second relapse. Second relapses occurring >26 months from the first relapse were associated with lower risk for post-HCT relapse compared with second relapses occurring at ≤26 months (relative risk, 0.4; P = .01). Relapse risk was lowest when late second relapse was preceded by late first relapse (>36 months from diagnosis), as demonstrated by a 3-year relapse rate of 9% (P = .0009). Our data indicate that long-term leukemia-free survival can be achieved in children with acute lymphoblastic leukemia in third remission using unrelated donor HCT, especially when the second relapse occurs late.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2011; 17(12):1833-40. · 3.15 Impact Factor
-
Ron Ram,
Rainer Storb,
Brenda M Sandmaier,
David G Maloney,
Ann Woolfrey, Mary E D Flowers,
Michael B Maris,
Ginna G Laport,
Thomas R Chauncey,
Thoralf Lange,
Amelia A Langston,
Barry Storer,
George E Georges
[show abstract]
[hide abstract]
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. · 6.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The controversy surrounding private banking of umbilical cord blood units (CBU), as a safeguard against future malignancy or other life-threatening conditions, raises many questions in pediatric clinical practice. Recent favorable experiences with autologous transplantation for severe aplastic anemia using privately stored CBU, suggested a possible utility. While private banking is difficult to justify statistically or empirically, there may exist rare cases where autologous transplant of stored umbilical CBU could be beneficial. The reality of privately banked CBU and the possibility for future discovery of additional indications for autologous cord blood transplant, motivated us to re-examine our attitudes towards private cord blood banking.
Pediatric Blood & Cancer 03/2011; 56(7):1009-12. · 1.89 Impact Factor
-
Eneida R Nemecek,
Katherine A Guthrie,
Mohamed L Sorror,
Brent L Wood,
Kristine C Doney,
Ralf A Hilger,
Bart L Scott,
Tibor J Kovacsovics,
Richard T Maziarz, Ann E Woolfrey,
Antonio Bedalov,
Jean E Sanders,
John M Pagel,
Eileen J Sickle,
Robert Witherspoon,
Mary E Flowers,
Frederick R Appelbaum,
H Joachim Deeg
[show abstract]
[hide abstract]
ABSTRACT: In this prospective study 60 patients of median age 46 (range: 5-60 years), with acute myelogenous leukemia (AML; n = 44), acute lymphoblastic leukemia (ALL; n = 3), or myelodysplastic syndrome (MDS; n = 13) were conditioned for allogeneic hematopoietic cell transplantation with a treosulfan/fludarabine (Flu) combination. Most patients were considered at high risk for relapse or nonrelapse mortality (NRM). Patients received intravenous treosulfan, 12 g/m(2)/day (n = 5) or 14 g/m(2)/day (n = 55) on days -6 to -4, and Flu (30 mg/m(2)/day) on days -6 to -2, followed by infusion of marrow (n = 7) or peripheral blood stem cells (n = 53) from HLA-identical siblings (n = 30) or unrelated donors (n = 30). All patients engrafted. NRM was 5% at day 100, and 8% at 2 years. With a median follow-up of 22 months, the 2-year relapse-free survival (RFS) for all patients was 58% and 88% for patients without high-risk cytogenetics. The 2-year cumulative incidence of relapse was 33% (15% for patients with MDS, 34% for AML in first remission, 50% for AML or ALL beyond first remission and 63% for AML in refractory relapse). Thus, a treosulfan/Flu regimen was well tolerated and yielded encouraging survival and disease control with minimal NRM. Further trials are warranted to compare treosulfan/Flu to other widely used regimens, and to study the impact of using this regimen in more narrowly defined groups of patients.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2011; 17(3):341-50. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Effectiveness of double umbilical cord blood (dUCB) grafts relative to conventional marrow and mobilized peripheral blood from related and unrelated donors has yet to be established. We studied 536 patients at the Fred Hutchinson Cancer Research Center and University of Minnesota with malignant disease who underwent transplantation with an human leukocyte antigen (HLA)-matched related donor (MRD, n = 204), HLA allele-matched unrelated donor (MUD, n = 152) or 1-antigen-mismatched unrelated adult donor (MMUD, n = 52) or 4-6/6 HLA matched dUCB (n = 128) graft after myeloablative conditioning. Leukemia-free survival at 5 years was similar for each donor type (dUCB 51% [95% confidence interval (CI), 41%-59%]; MRD 33% [95% CI, 26%-41%]; MUD 48% [40%-56%]; MMUD 38% [95% CI, 25%-51%]). The risk of relapse was lower in recipients of dUCB (15%, 95% CI, 9%-22%) compared with MRD (43%, 95% CI, 35%-52%), MUD (37%, 95% CI, 29%-46%) and MMUD (35%, 95% CI, 21%-48%), yet nonrelapse mortality was higher for dUCB (34%, 95% CI, 25%-42%), MRD (24% (95% CI, 17%-39%), and MUD (14%, 95% CI, 9%-20%). We conclude that leukemia-free survival after dUCB transplantation is comparable with that observed after MRD and MUD transplantation. For patients without an available HLA matched donor, the use of 2 partially HLA-matched UCB units is a suitable alternative.
Blood 11/2010; 116(22):4693-9. · 9.90 Impact Factor
-
Lauri M Burroughs,
Troy R Torgerson,
Rainer Storb,
Paul A Carpenter,
David J Rawlings,
Jean Sanders,
Andrew M Scharenberg,
Suzanne Skoda-Smith,
Janet Englund,
Hans D Ochs, Ann E Woolfrey
[show abstract]
[hide abstract]
ABSTRACT: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is characterized by severe systemic autoimmunity caused by mutations in the forkhead box protein 3 (FOXP3) gene. Hematopoietic cell transplantation is currently the only viable option for long-term survival, but patients are frequently very ill and may not tolerate traditional myeloablative conditioning regimens.
Here we present the outcome of hematopoietic cell transplantation using a low-intensity, nonmyeloablative conditioning regimen in 2 patients with IPEX syndrome and significant pretransplant risk factors.
Two high-risk patients with IPEX syndrome received HLA-matched related bone marrow or unrelated peripheral blood stem cell grafts following conditioning with 90 mg/m(2) fludarabine and 4 Gy total body irradiation. Postgrafting immunosuppression consisted of mycophenolate mofetil and cyclosporine. Immune reconstitution and immune function was evaluated by measurement of donor chimerism, regulatory T-cell numbers, absolute lymphocyte subsets, and T-cell proliferation assays.
Both patients experienced minimal conditioning toxicity and successfully engrafted after hematopoietic cell transplantation. With a follow-up of 4 and 1 years, respectively, patients 1 and 2 have full immune function and normal FOXP3 protein expression.
A low-intensity, nonmyeloablative conditioning regimen can establish stable engraftment and correct the life-threatening immune deficiency and enteropathy of IPEX syndrome despite the presence of comorbidities that preclude conventional hematopoietic cell transplantation.
The Journal of allergy and clinical immunology 11/2010; 126(5):1000-5. · 9.17 Impact Factor
-
Matt E Kalaycio,
Manisha Kukreja, Ann E Woolfrey,
Jeffrey Szer,
Jorge Cortes,
Richard T Maziarz,
Brian J Bolwell,
Andreas Buser,
Edward Copelan,
Robert Peter Gale,
Vikas Gupta,
Dipnarine Maharaj,
David I Marks,
Steven Z Pavletic,
Mary M Horowitz,
Mukta Arora
[show abstract]
[hide abstract]
ABSTRACT: The poor prognosis of patients with prolymphocytic leukemia (PLL) has led some clinicians to recommend allogeneic hematopoietic cell transplant (HCT). However, the data to support this approach is limited to case-reports and small case series. We reviewed the database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to determine outcomes after allotransplant for patients with PLL. We identified 47 patients with a median age of 54 years (range: 30-75 years). With a median follow-up of 13 months, progression-free survival (PFS) was 33% (95% confidence interval [CI] 20%-47%) at 1 year. The most common cause of death was relapse or progression in 49%. The cumulative incidence of treatment-related mortality (TRM) at 1-year posttransplant was 28%. The small patient population prohibited prognostic factor analysis, but these data support consideration of allotransplant for PLL. Further study of a larger population of patients is needed to determine which patients are more likely to benefit.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2009; 16(4):543-7. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Growing evidence supports the efficacy of cord blood transplantation (CBT), and the number of CBTs is increasing. Numerous studies confirm the presence of a graft-versus-leukemia (GVL) effect following CBT, and preliminary data suggests that double-unit CBT may be associated with a decreased risk of relapse. We have observed a low relapse rate following CBT among patients with acute leukemias in morphologic complete remission (CR) at the time of myeloablative (MA) transplant. To further assess this observation, we conducted a matched cohort analysis comparing relapse rates and outcomes for patients receiving CBTs versus patients receiving matched unrelated donor (MURD) and mismatched unrelated donor (MMURD) transplants at our center. Thirty-one consecutive CBT patients (aged 0.6-42 years, median 22 years), transplanted between April 2006 and June 2008, were compared to matched subjects selected on the basis of disease type and remission number, cytogenetic risk status, minimal residual disease status (MRD), time from diagnosis to first relapse (for patients beyond CR1), use of imatinib for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) patients, age, and date of transplant. With a median follow-up among surviving CBT patients of 21.1 months (range: 6.6-32.6 months), there has been 1 relapse among cord patients versus 8 relapses among MURD patients (P=.018) and 7 relapses among MMURD patients (P=.019). Treatment-related mortality (TRM) between cohorts is comparable. Although we have observed a high incidence of acute graft-versus-host disease (aGVHD) following CBT, the incidence of National Institutes of Health (NIH) consensus criteria chronic GVHD (cGVHD) has been low. These data support increased investigation of the use of CBT.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2009; 15(9):1122-9. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Preformed host antibodies may contribute to graft rejection after hematopoietic stem-cell transplantation. In cord blood transplantation (CBT), donor-directed host antibodies may be particularly relevant because patients are often markedly mismatched to donors, and limited donor cells preclude cross-matching. The recent development of single human leukocyte antigen (HLA) microbead array assays allows characterization of host alloreactivity to individual HLA antigens with sufficient sensitivity and specificity to allow consideration of "virtual crossmatch" testing as a surrogate for conventional crossmatch testing in the CBT setting. We report results of prospective monitoring for alloimmunization in our recent CBT experience. Among 46 consecutive patients, four patients (9%) (5 of 88 units [6%]) had evidence of at least moderate antibodies to HLA antigens on cord units originally selected for transplantation. Virtual crossmatch can be used to screen for donor-directed antibodies in CBT. As possible, units should be changed to avoid sensitized mismatches.
Transplantation 03/2009; 87(3):415-8. · 4.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Thyroid dysfunction is a known complication after hematopoietic cell transplantation (HCT) in children with reports involving relatively short follow-up and small patient numbers. This study involves 791 patients less than 18 years of age at HCT at the Fred Hutchinson Cancer Research Center with follow-up from 1969 through 2007. Thyroid dysfunction continued for 28 years after transplantation. Hypothyroidism was the most common abnormality with other abnormalities of hyperthyroidism and thyroiditis. Multivariate analysis showed that thyroid dysfunction was more likely if patients were less than 10 years of age (P < .001), but there was no difference between receiving a total body irradiation or busulfan based regimens (P = .48) compared with cyclophosphamide conditioning alone (P = .008). Thyroid tumors occurred at a median of 9.9 (4.5-22.3) years after HCT and included 13 with papillary carcinoma and 5 with benign adenomas. Children who receive a HCT should be monitored for thyroid abnormalities throughout life.
Blood 10/2008; 113(2):306-8. · 9.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study tested whether donor-derived HIV-specific immune responses could be detected when viral replication was completely suppressed by the continuous administration of highly active antiretroviral therapy (HAART). A regimen of fludarabine and 200 cGy total body irradiation was followed by infusion of allogeneic donor peripheral blood cells and posttransplantation cyclosporine and mycophenolate mofetil. Viral load, lymphocyte counts, and HIV-1-specific CD8(+) cell immune responses were compared before and after hematopoietic cell transplantation (HCT). Uninterrupted administration of HAART was feasible during nonmyeloablative conditioning and after HCT. The HIV RNA remained undetectable and no HIV-associated infections were observed. CD8(+) T-cell responses targeting multiple epitopes were detected before HCT. After HCT a different pattern of donor-derived HIV-specific CTL responses emerged by day +80, presumably primed in vivo. We conclude that allogeneic HCT offers the unique ability to characterize de novo HIV-1-specific immune responses. This clinical trial was registered at ClinicalTrials.gov (identifier: NCT00112593).
Blood 09/2008; 112(8):3484-7. · 9.90 Impact Factor
-
Stephanie J Lee,
Manisha Kukreja, Tao Wang,
Sergio A Giralt,
Jeffrey Szer,
Mukta Arora, Ann E Woolfrey,
Francisco Cervantes,
Richard E Champlin,
Robert Peter Gale, [......],
Joseph H Antin,
Brian J Bolwell,
Matthew H Carabasi,
Edward Copelan,
Osman Ilhan,
Mark R Litzow,
Harold C Schouten,
Axel R Zander,
Mary M Horowitz,
Richard T Maziarz
[show abstract]
[hide abstract]
ABSTRACT: Imatinib mesylate (IM, Gleevec) has largely supplanted allogeneic hematopoietic cell transplantation (HCT) as first line therapy for chronic myeloid leukemia (CML). Nevertheless, many people with CML eventually undergo HCT, raising the question of whether prior IM therapy impacts HCT success. Data from the Center for International Blood and Marrow Transplant Research on 409 subjects treated with IM before HCT (IM(+)) and 900 subjects who did not receive IM before HCT (IM(-)) were analyzed. Among patients in first chronic phase, IM therapy before HCT was associated with better survival but no statistically significant differences in treatment-related mortality, relapse, and leukemia-free survival. Better HLA-matched donors, use of bone marrow, and transplantation within one year of diagnosis were also associated with better survival. A matched-pairs analysis was performed and confirmed a higher survival rate among first chronic phase patients receiving IM. Among patients transplanted with advanced CML, use of IM before HCT was not associated with treatment-related mortality, relapse, leukemia-free survival, or survival. Acute graft-versus-host disease rates were similar between IM(+) and IM(-) groups regardless of leukemia phase. These results should be reassuring to patients receiving IM before HCT.
Blood 08/2008; 112(8):3500-7. · 9.90 Impact Factor
-
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
[show abstract]
[hide abstract]
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
