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Mehdi Hamadani,
Wael Saber,
Kwang Woo Ahn, Jeanette Carreras,
Mitchell S Cairo,
Timothy S Fenske,
Robert Peter Gale,
John Gibson,
Gregory A Hale,
Parameswaran N Hari, [......],
David I Marks,
David A Rizzieri,
Bipin N Savani,
Harry C Schouten,
Edmund K Waller,
Baldeep Wirk,
Ginna G Laport,
Silvia Montoto,
David G Maloney,
Hillard M Lazarus
[show abstract]
[hide abstract]
ABSTRACT: Patients with chemorefractory non-Hodgkin lymphomas (NHL) generally have a poor prognosis. We used the observational database of the CIBMTR to study the outcome of 533 patients with refractory diffuse large B-cell lymphoma (DLBCL) or grade-III follicular lymphoma (FL-III) who underwent allogeneic transplantation (allo-HCT) using either myeloablative (MA; N=307) or reduced intensity/non-myeloablative conditioning (RIC/NST; N=226), between 1998-2010. We analyzed non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Only 45% of the patients at transplant had a Karnofsky performance score of ≥90%. Median follow-up of surviving patients after MA and RIC/NST allo-HCT is 35 months and 30 months, respectively. At 3years, MA allo-HCT was associated with a higher NRM compared to RIC/NST (53% vs. 42%; p=0.03), similar PFS (19% vs. 23%; p=0.40), and lower OS (19% vs. 28%; p=0.02), respectively. On multivariate analysis, FL-III histology was associated with lower NRM (relative-risk [RR]=0.52), reduced risk of relapse/progression (RR=0.42), superior PFS (RR=0.51) and OS (RR=0.53), while MA conditioning was associated with reduced risk of relapse/progression (RR=0.66). Despite a refractory state, a small subset of DLBCL and FL-III patients can attain durable remissions after allo-HCT. Conditioning regimen intensity was not associated with PFS and OS despite a higher risk of relapse/progression with RIC/NST allo-HCT.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2013; · 3.15 Impact Factor
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Mehdi Hamadani,
Wael Saber,
Kwang Woo Ahn, Jeanette Carreras,
Mitchell S Cairo,
Timothy S Fenske,
Robert Peter Gale,
John Gibson,
Gregory A Hale,
Parameswaran N Hari, [......],
Rammurti T Kamble,
Anderas Klein,
Dipnarine Maharaj,
David I Marks,
David A Rizzieri,
Bipin N Savani,
Harry C Schouten,
Edmund K Waller,
Baldeep Wirk,
Hillard M Lazarus
[show abstract]
[hide abstract]
ABSTRACT: Patients with chemorefractory mantle cell lymphoma (MCL) have poor prognosis. We used the CIBMTR database to study the outcome of 202 patients with refractory MCL who underwent allogeneic hematopoietic cell transplantation (allo-HCT) using either myeloablative (MA) or reduced intensity/non-myeloablative conditioning (RIC/NST), during 1998-2010. We analyzed non-relapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS). Seventy-four patients received MA, and 128 underwent RIC/NST. Median ages are 54 and 59 years for MA and RIC/NST allo-HCT recipients, respectively. Median follow-up after MA and RIC/NST allo-HCT is 35 months and 43 months, respectively. At 3 years, comparing MA with RIC/NST allo-HCT, no significant differences were found in terms of NRM (47% vs. 43%; p-value=0.68), relapse/progression (33% vs. 32%; p-value=0.89), PFS (20% vs. 25%; p=0.53), and OS (25% vs. 30%; p-value=0.45). On multivariate analysis no significant differences were observed in NRM, relapse, PFS and OS between MA and RIC/NST allo-HCT; however, receiving a bone marrow or T-cell depleted allograft was associated with an increased risk of NRM and inferior PFS and OS. Despite a refractory disease state, approximately a fourth of MCL patients can attain durable remissions after allo-HCT. Conditioning regimen intensity did not influence the outcomes of patients after allo HCT.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2013; · 3.15 Impact Factor
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Leena V Maramattom,
Parameswaran N Hari,
Linda J Burns, Jeanette Carreras,
William Arcese,
Mitchell S Cairo,
Luciano J Costa,
Timothy S Fenske,
Michael Lill,
Cesar O Freytes, [......],
Jack W Hsu,
David J Inwards,
Hillard M Lazarus,
David I Marks,
David G Maloney,
Richard T Maziarz,
Silvia Montoto,
David A Rizzieri,
Baldeep Wirk,
James L Gajewski
[show abstract]
[hide abstract]
ABSTRACT: Trends in utilization and outcomes after autologous or allogeneic hematopoietic cell transplantation (HCT) for Burkitt Lymphoma (BL) were analyzed in 241 recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 1985 and 2007. The autologous HCT cohort had a higher proportion with chemotherapy sensitive disease, peripheral blood grafts and HCT in first complete remission (CR1). The use of autologous HCT has declined over time with only 19% done after 2001. Overall survival (OS) at 5 years for the autologous cohort was 83% for those in CR1, and 31% for non-CR1 recipients. Corresponding progression free survival (PFS) was 78% and 27%, respectively. After allogeneic HCT, OS at 5 years was 53% and 20% for the CR1 and non-CR1 cohorts while PFS was 50% and 19%, respectively. The most common cause of death was progressive lymphoma. Allogeneic HCT performed in a higher risk subset (per NCCN guidelines) resulted in a 5 year PFS of 27%. Autologous HCT, resulted in a 5 year PFS of 44% in those transplanted in second CR.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2012; · 3.15 Impact Factor
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Minoo Battiwalla, Tao Wang, Jeanette Carreras,
H Joachim Deeg,
Mouhab Ayas,
Rajinder P S Bajwa,
Biju George,
Vikas Gupta,
Ricardo Pasquini,
Hubert Schrezenmeier,
Jakob R Passweg,
Kirk R Schultz,
Mary Eapen
[show abstract]
[hide abstract]
ABSTRACT: The HLA class II DRB1 antigen DR15 (common alleles *1501, *1502) is an important marker in the pathobiology of severe aplastic anemia (SAA). We studied 1204 recipients of HLA-matched sibling bone marrow transplantation for SAA to determine whether HLA DR15 status (as determined by allele-level typing) affected hematopoietic recovery, graft-versus-host disease (GVHD), or overall survival (OS). In multivariate analysis, secondary graft failure rate at 2 years was lower in patients who were HLA DR15+ (hazard ratio = 0.46, P = .01). However, neutrophil recovery at day -28, platelet recovery at day -100, acute GVHD, chronic GVHD, and overall mortality were independent of DR15 status. The 5-year probabilities of OS, after adjusting for age, race, performance score, transplant-conditioning regimen, and year of transplantation, were 78% and 81% for patients who were HLA DR15+ and HLA DR15-, respectively (P = .35). In conclusion, DR15 status is associated with secondary graft failure after HLA-matched sibling bone marrow transplantation for SAA but has no significant impact on survival.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2012; 18(9):1401-6. · 3.15 Impact Factor
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César O Freytes,
Mei-Jie Zhang, Jeanette Carreras,
Linda J Burns,
Robert Peter Gale,
Luis Isola,
Miguel-Angel Perales,
Matthew Seftel,
Julie M Vose,
Alan M Miller, [......],
Rodrigo Martino,
David I Marks,
Gregory A Hale,
Sonali M Smith,
Harry C Schouten,
Simon Slavin,
Thomas R Klumpp,
Hillard M Lazarus,
Koen van Besien,
Parameswaran N Hari
[show abstract]
[hide abstract]
ABSTRACT: We studied the outcome of allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning regimens (reduced-intensity conditioning and nonmyeloablative) in patients with non-Hodgkin lymphoma who relapsed after autologous hematopoietic stem cell transplantation. Nonrelapse mortality, lymphoma progression/relapse, progression-free survival (PFS), and overall survival were analyzed in 263 patients with non-Hodgkin lymphoma. All 263 patients had relapsed after a previous autologous hematopoietic stem cell transplantation and then had undergone allogeneic hematopoietic stem cell transplantation from a related (n = 26) or unrelated (n = 237) donor after reduced-intensity conditioning (n = 128) or nonmyeloablative (n = 135) and were reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2006. The median follow-up of survivors was 68 months (range, 3-111 months). Three-year nonrelapse mortality was 44% (95% confidence interval [CI], 37%-50%). Lymphoma progression/relapse at 3 years was 35% (95% CI, 29%-41%). Three-year probabilities of PFS and overall survival were 21% (95% CI, 16%-27%) and 32% (95% CI, 27%-38%), respectively. Superior Karnofsky Performance Score, longer interval between transplantations, total body irradiation-based conditioning regimen, and lymphoma remission at transplantation were correlated with improved PFS. Allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning is associated with significant nonrelapse mortality but can result in long-term PFS. We describe a quantitative risk model based on pretransplantation risk factors to identify those patients likely to benefit from this approach.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2011; 18(8):1255-64. · 3.15 Impact Factor
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Mary Eapen,
Jennifer Le Rademacher,
Joseph H Antin,
Richard E Champlin, Jeanette Carreras,
Joseph Fay,
Jakob R Passweg,
Jakub Tolar,
Mary M Horowitz,
Judith C W Marsh,
H Joachim Deeg
[show abstract]
[hide abstract]
ABSTRACT: Outcome after unrelated donor bone marrow (BM) transplantation for severe aplastic anemia (SAA) has improved, with survival rates now approximately 75%. Increasing use of peripheral blood stem and progenitor cells (PBPCs) instead of BM as a graft source prompted us to compare outcomes of PBPC and BM transplantation for SAA. We studied 296 patients receiving either BM (n = 225) or PBPC (n = 71) from unrelated donors matched at human leukocyte antigen-A, -B, -C, -DRB1. Hematopoietic recovery was similar after PBPC and BM transplantation. Grade 2 to 4 acute graft-versus-host disease risks were higher after transplantation of PBPC compared with BM (hazard ratio = 1.68, P = .02; 48% vs 31%). Chronic graft-versus-host disease risks were not significantly different after adjusting for age at transplantation (hazard ratio = 1.39, P = .14). Mortality risks, independent of age, were higher after PBPC compared with BM transplantation (hazard ratio = 1.62, P = .04; 76% vs 61%). These data indicate that BM is the preferred graft source for unrelated donor transplantation in SAA.
Blood 06/2011; 118(9):2618-21. · 9.90 Impact Factor
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Vikas Gupta,
Mary Eapen,
Ruta Brazauskas, Jeanette Carreras,
Mahmoud Aljurf,
Robert Peter Gale,
Gregory A Hale,
Osman Ilhan,
Jakob R Passweg,
Ollé Ringdén,
Mitchell Sabloff,
Hubert Schrezenmeier,
Gerard Socié,
Judith C W Marsh
[show abstract]
[hide abstract]
ABSTRACT: Transplantation from an HLA-matched sibling is the treatment of choice for young patients with acquired severe aplastic anemia. For older patients, the acceptable upper age limit for transplantation as first-line treatment varies. The current analysis, therefore, sought to identify age or ages at transplantation at which survival differed.
We studied the effect of patients' age, adjusting for other significant factors affecting outcomes, in 1307 patients with severe aplastic anemia after HLA-matched sibling transplantation using logistic and Cox regression analysis. Age categories (<20 years, 20-40 years, >40 years) were determined using Martingale residual plots for overall survival and categories based on differences in survival.
Patients aged over 40 years old were more likely to have had immunosuppressive therapy, a poor performance score and a longer interval between diagnosis and transplantation. Neutrophil recovery was similar in all age groups but patients aged over 40 years had a lower likelihood of platelet recovery compared to patients aged less than 20 years (OR 0.45, P=0.01) but not compared to those aged 20-40 years (OR 0.60, P=0.10). Compared to the risk of mortality in patients aged less than 20 years, mortality risks were higher in patients over 40 years old (RR 2.70, P<0.0001) and in those aged 20-40 years (RR 1.69, P<0.0001). The mortality risk was also higher in patients aged over 40 years than in those 20-40 years old (RR 1.60, P=0.008).
Mortality risks increased with age. Risks were also higher in patients with a poor performance score and when the interval between diagnosis and transplantation was longer than 3 months, implying earlier referral would be appropriate when this treatment option is being considered.
Haematologica 12/2010; 95(12):2119-25. · 6.42 Impact Factor
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Hillard M Lazarus,
Mei-Jie Zhang, Jeanette Carreras,
Brandon M Hayes-Lattin,
Asli Selmin Ataergin,
Jacob D Bitran,
Brian J Bolwell,
César O Freytes,
Robert Peter Gale,
Steven C Goldstein, [......],
Philip L McCarthy,
Santiago Pavlovsky,
J Douglas Rizzo,
Thomas C Shea,
Harry C Schouten,
Shimon Slavin,
Jane N Winter,
Koen van Besien,
Julie M Vose,
Parameswaran N Hari
[show abstract]
[hide abstract]
ABSTRACT: We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients aged >or=18 years undergoing first autologous (n = 837) or myeloablative (MA) allogeneic hematopoietic cell transplant (HCT) (n = 79) between 1995 and 2003 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Median follow-up was 81 months for allogeneic HCT versus 60 months for autologous HCT. Allogeneic HCT recipients were more likely to have high-risk disease features including higher stage, more prior chemotherapy regimens, and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (relative risk [RR] 4.88, 95% confidence interval [CI], 3.21-7.40, P < .001), treatment failure (RR 2.06, 95% CI, 1.54-2.75, P < .001), and mortality (RR 2.75, 95% CI, 2.03-3.72, P < .001). Risk of disease progression was similar in the 2 groups (RR 1.12, 95% CI, 0.73-1.72, P = .59). In fact, for 1-year survivors, no significant differences were observed for TRM, progression, progression-free (PFS) or overall survival (OS). Increased risks of TRM and mortality were associated with older age (>50 years), lower performance score, chemoresistance, and earlier year of transplant. In a cohort of mainly high-risk DLBCL patients, upfront MA allogeneic HCT, although associated with increased early mortality, was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2010; 16(1):35-45. · 3.15 Impact Factor
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Timothy S Fenske,
Parameswaran N Hari, Jeanette Carreras,
Mei-Jie Zhang,
Rammurti T Kamble,
Brian J Bolwell,
Mitchell S Cairo,
Richard E Champlin,
Yi-Bin Chen,
César O Freytes, [......],
Andrew L Pecora,
Philip A Rowlings,
Thomas C Shea,
Patrick Stiff,
Peter H Wiernik,
Jane N Winter,
J Douglas Rizzo,
Koen van Besien,
Hillard M Lazarus,
Julie M Vose
[show abstract]
[hide abstract]
ABSTRACT: Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens to treat diffuse large B cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, however, many patients develop refractory or recurrent DLBCL and then undergo autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes after AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n = 176; +R cohort) or was not (n = 818; -R cohort) administered with front-line or salvage therapy before AuHCT. The +R cohort had superior progression-free survival (PFS; 50% vs 38%; P = .008) and overall survival (OS; 57% vs 45%; P = .006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Nonrelapse mortality (NRM) did not differ significantly between the 2 cohorts. In multivariate analysis, the +R cohort had improved PFS (relative risk of relapse/progression or death, 0.64; P < .001) and improved OS (relative risk of death, 0.74; P = .039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival after AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2009; 15(11):1455-64. · 3.15 Impact Factor
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Koen van Besien, Jeanette Carreras,
Philip J Bierman,
Brent R Logan,
Arturo Molina,
Roberta King,
Gene Nelson,
Joseph W Fay,
Richard E Champlin,
Hillard M Lazarus,
Julie M Vose,
Parameswaran N Hari
[show abstract]
[hide abstract]
ABSTRACT: We analyzed the outcomes of 283 patients receiving unrelated donor allogeneic hematopoietic cell transplantation for non-Hodgkin lymphoma (NHL) facilitated by the Center for International Blood and Marrow Transplant Research/National Marrow Donor Program (CIBMTR/NMDP) between 1991 and 2004. All patients received myeloablative conditioning regimens. The median follow-up of survivors is 5 years. Seventy-three (26%) patients are alive. The day 100 probability of death from all causes is estimated at 39%. The cumulative incidence of developing grade III-IV acute graft-versus-host disease (aGVHD) at day 100 is 25%. The estimated 5-year survival and failure free survival are 24% (95% confidence interval [CI]: 19-30) and 22% (95% CI: 17-28), respectively. Factors adversely associated with overall survival (OS) included increasing age, decreased performance status, and refractory disease. Follicular lymphoma (FL) and peripheral T cell lymphoma had improved survival compared to aggressive B cell lymphomas. Factors adversely associated with progression-free survival (PFS) included performance status, histology, and disease status at transplant. Long-term failure-free survival is possible following unrelated donor transplantation for NHL, although early mortality was high in this large cohort.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2009; 15(5):554-63. · 3.15 Impact Factor
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John T Horan, Jeanette Carreras,
Sergey Tarima,
Bruce M Camitta,
Robert Peter Gale,
Gregory A Hale,
Wolfgang Hinterberger,
Judith Marsh,
Jakob R Passweg,
Mark C Walters,
Mary Eapen
[show abstract]
[hide abstract]
ABSTRACT: We examined transplantation outcomes after a second HLA-matched sibling transplantation for primary (16%) or secondary (84%) graft failure in 166 patients with severe acquired aplastic anemia (AA). Two-thirds of these patients has a performance score < 90. In most cases (88%), the same donor was used for both transplants, for both transplantations, and 84% of the second transplantations used bone marrow grafts. We identified 2 prognostic factors: intertransplantation interval (surrogate for primary graft failure and early secondary graft failure) and performance status. Shorter intertransplantation interval (<or= 3 months) and poor performance score (< 90) at second transplantation were associated with high mortality. In patients with a performance score of 90% to 100%, the 8-year probability of overall survival (OS) after second transplantation <or= 3 and > 3 months from first transplantation was 56% and 76%, respectively. The corresponding probabilities in patients with lower performance scores were 33% and 61%. The predominant cause of failure after second transplantation was nonengraftment (in 72 of 166 patients), most commonly in patients with primary or early secondary graft failure (51 of 72; 71%). Our data indicate that novel approaches, including conditioning regimens with greater immunosuppression, should be explored for these patients.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2009; 15(5):626-31. · 3.15 Impact Factor
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Marcel P Devetten,
Parameswaran N Hari, Jeanette Carreras,
Brent R Logan,
Koen van Besien,
Christopher N Bredeson,
César O Freytes,
Robert Peter Gale,
John Gibson,
Sergio A Giralt,
Steven C Goldstein,
Vikas Gupta,
David I Marks,
Richard T Maziarz,
Julie M Vose,
Hillard M Lazarus,
Paolo Anderlini
[show abstract]
[hide abstract]
ABSTRACT: Myeloablative allogeneic hematopoietic cell transplantation (HCT) may cure patients with relapsed or refractory Hodgkin lymphoma (HL), but is associated with a high treatment-related mortality (TRM). Reduced-intensity and nonmyeloablative (RIC/NST) conditioning regimens aim to lower TRM. We analyzed the outcomes of 143 patients undergoing unrelated donor RIC/NST HCT for relapsed and refractory HL between 1999 and 2004 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Patients were heavily pretreated, including autologous HCT in 89%. With a median follow-up of 25 months, the probability of TRM at day 100 and 2 years was 15% (95% confidence interval [CI] 10%-21%) and 33% (95% CI 25%-41%), respectively. The probabilities of progression free survival (PFS) and overall survival (OS) were 30% and 56% at 1 year and 20% and 37% at 2 years. The presence of extranodal disease and the Karnofsky Performance Scale (KPS) <90 were significant risk factors for TRM, PFS, and OS, whereas chemosensitivity at transplantation was not. Dose intensity of the conditioning regimen (RIC versus NST) did not impact outcomes. Unrelated donor HCT with RIC/NST can salvage some patients with relapsed/refractory HL, but relapse remains a common reason for treatment failure. Clinical studies should be aimed at reducing the incidence of acute graft-versus-host disease (GVHD) and relapse.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2009; 15(1):109-17. · 3.15 Impact Factor
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Hillard M Lazarus, Jeanette Carreras,
Christian Boudreau,
Fausto R Loberiza,
James O Armitage,
Brian J Bolwell,
César O Freytes,
Robert Peter Gale,
John Gibson,
Gregory A Hale, [......],
Koen van Besien,
Julie M Vose,
Jacob D Bitran,
Issa F Khouri,
Philip L McCarthy,
Hongmei Yu,
Philip Rowlings,
Derek S Serna,
Mary M Horowitz,
J Douglas Rizzo
[show abstract]
[hide abstract]
ABSTRACT: To compare the clinical outcomes of older (age > or =55 years) non-Hodgkin lymphoma (NHL) patients with younger NHL patients (<55 years) receiving autologous hematopoietic cell transplantation (HCT) while adjusting for patient-, disease-, and treatment-related variables, we compared autologous HCT outcomes in 805 NHL patients aged > or =55 years to 1949 NHL patients <55 years during the years 1990-2000 using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). In multivariate analysis, older patients with aggressive histologies were 1.86 times (95% confidence interval [CI] 1.43-2.43, P < .001) more likely than younger patients to experience treatment-related mortality (TRM). Relative death risks were 1.33 times (CI 1.04-1.71, P = .024) and 1.50 times (CI 1.33-16.9, P < .001) higher in older compared to younger patients with follicular grade I/II and aggressive histologies, respectively. Autologous HCT in older NHL patients is feasible, but most disease-related outcomes are statistically inferior to younger patients. Studies addressing supportive care particular to older patients, who are most likely to benefit from this approach, are recommended.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2009; 14(12):1323-33. · 3.15 Impact Factor
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Ricardo Pasquini, Jeanette Carreras,
Marcelo C Pasquini,
Bruce M Camitta,
Anders L Fasth,
Gregory A Hale,
Richard E Harris,
Judith C Marsh,
Anibal J Robinson,
Mei-Jie Zhang,
Mary Eapen,
John E Wagner
[show abstract]
[hide abstract]
ABSTRACT: Related to the underlying DNA repair defect that is the hallmark of Fanconi anemia (FA), preparatory regimen-related toxicities have been obstacles to hematopoietic cell transplantation (HCT). In an attempt to decrease the risk and severity of regimen-related toxicities, nonirradiation regimens have been explored. The aim of this study is to compare outcomes after irradiation and nonirradiation regimens in 148 FA patients and identify risk factors impacting upon HCT outcomes. Hematopoietic recovery, acute and chronic graft-versus-host disease (aGVHD, GVHD), and mortality were similar after irradiation and nonirradiation regimens. In both groups of recipients aged >10 years, prior use of androgens and cytomegalovirus seropositivity in either the donor or recipient were associated with higher mortality. With median follow-ups >5 years, the 5-year probability of overall survival, adjusted for factors impacting overall mortality was 78% and 81% after irradiation and nonirradiation regimens, P = .61. In view of the high risk of cancer and other radiation-related effects on growth and development, these results support the use of nonirradiation preparatory regimens. As the peak time for developing solid tumors after HCT is 8 to 9 years, longer follow-up is required before definitive statements can be made regarding the impact of nonirradiation regimens on cancer risk.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2008; 14(10):1141-7. · 3.15 Impact Factor
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Sonali M Smith,
Koen van Besien, Jeanette Carreras,
Asad Bashey,
Mitchell S Cairo,
Cesar O Freytes,
Robert Peter Gale,
Gregory A Hale,
Brandon Hayes-Lattin,
Leona A Holmberg, [......],
Richard T Maziarz,
Philip L McCarthy,
Willis H Navarro,
Santiago Pavlovsky,
Harry C Schouten,
Matthew Seftel,
Peter H Wiernik,
Julie M Vose,
Hillard M Lazarus,
Parameswaran Hari
[show abstract]
[hide abstract]
ABSTRACT: We determined treatment-related mortality, progression-free survival (PFS), and overall survival (OS) after a second autologous HCT (HCT2) for patients with lymphoma relapse after a prior HCT (HCT1). Outcomes for patients with either Hodgkin lymphoma (HL, n = 21) or non-Hodgkin lymphoma (NHL, n = 19) receiving HCT2 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) were analyzed. The median age at HCT2 was 38 years (range: 16-61) and 22 (58%) patients had a Karnofsky performance score <90. HCT2 was performed >1 year after HCT1 in 82%. The probability of treatment-related mortality at day 100 was 11% (95% confidence interval [CI], 3%-22%). The 1-, 3-, and 5-year probabilities of PFS were 50% (95% CI, 34%-66%), 36% (95% CI, 21%-52%), and 30% (95% CI, 16%-46%), respectively. Corresponding probabilities of survival were 65% (95% CI, 50%-79%), 36% (95% CI, 22%-52%), and 30% (95% CI, 17%-46%), respectively. At a median follow-up of 72 months (range: 12-124 months) after HCT2, 29 patients (73%) have died, 18 (62%) secondary to relapsed lymphoma. The outcomes of patients with HL and NHL were similar. In summary, this series represents the largest reported group of patients with relapsed lymphomas undergoing SCT2 following failed SCT1, and with long-term follow-up. Our series suggests that SCT2 is feasible in patients relapsing after prior HCT1, with a lower treatment-related mortality than that reported for allogeneic transplant in this setting. HCT2 should be considered for patients with relapsed HL or NHL after HCT1 without alternative allogeneic stem cell transplant options.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 08/2008; 14(8):904-12. · 3.15 Impact Factor
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Parameswaran Hari, Jeanette Carreras,
Mei-Jie Zhang,
Robert Peter Gale,
Brian J Bolwell,
Christopher N Bredeson,
Linda J Burns,
Mitchell S Cairo,
César O Freytes,
Steven C Goldstein,
Gregory A Hale,
David J Inwards,
Charles F Lemaistre,
Dipnarine Maharaj,
David I Marks,
Harry C Schouten,
Shimon Slavin,
Julie M Vose,
Hillard M Lazarus,
Koen van Besien
[show abstract]
[hide abstract]
ABSTRACT: Reduced-intensity conditioning (RIC) regimens have been increasingly used for allogeneic hematopoietic stem cell transplantation (HSCT) in follicular lymphoma (FL). We compared traditional myeloablative conditioning regimens to RIC in FL. Outcomes of HLA-identical sibling HSCT for FL in 208 recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 1997 and 2002 were studied. Conditioning regimens were categorized as myeloablative (N = 120) or RIC (N = 88). Use of RIC regimens increased from <10% of transplants in 1997 to >80% in 2002 signaling a major shift in practice. Patients receiving RIC were older and had a longer interval from diagnosis to transplant. These differences did not correlate with outcomes. Median follow-up of survivors was 50 months (4-96 months) after myeloablative conditioning versus 35 months (4-82 months) after RIC (P < .001). At 3 years, overall survival (OS) for the myeloablative and RIC cohorts were 71 (63%-79%) and 62 (51%-72%; P = .15) and progression free survival (PFS), 67 (58%-75%) and 55 (44%-65%; P = .07), respectively. Lower Karnofsky performance score (KPS) and resistance to chemotherapy were associated with higher treatment-related mortality (TRM) and lower OS and PFS. On multivariate analysis, an increased risk of lymphoma progression after RIC was observed (relative risk = 2.97, P = .04). RIC has become the de facto standard in allogeneic HSCT for FL, and appears to result in similar long-term outcomes. Although disease-free survival (DPS) is similar compared to myeloablative conditioning, an increased risk of late disease progression after RIC is concerning.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2008; 14(2):236-45. · 3.15 Impact Factor
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Hillard M Lazarus,
Patrick J Stiff, Jeanette Carreras,
Brent R Logan,
Luke Akard,
Brian J Bolwell,
Richard W Childs,
Robert Peter Gale,
John P Klein,
Michael C Lill,
Waleska S Pérez,
Edward A Stadtmauer,
J Douglas Rizzo
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ABSTRACT: Tandem autotransplants are used to treat advanced testis cancer patients but their value compared to a single autotransplant is unknown. To evaluate the results of autotransplant in relapsed testicular/germ cell cancer, data from 300 patients undergoing autotransplants 1989-2002 were reported to the Center for International Blood and Marrow Transplant Research. We compared results for those patients intended to undergo tandem autotransplant procedures (N = 102) versus patients in whom a second autotransplant was not planned (N = 198). Five-year survival probability was 35% (95% confidence interval = 25%-46%) in the planned tandem transplant cohort compared to 42% (35%-49%) in the group not planned to have a second transplant (P = .29). Probability of progression-free survival at 5 years for these cohorts was 34% (25%-44%) and 38% (31%-45%), respectively (P = .50). The planned tandem autotransplant cohort had significantly more advanced disease at diagnosis and greater likelihood of cisplatin resistance. Patients intended to receive tandem transplants had a lower treatment-related mortality at 1 year (3% versus 10%, P = .02). Using propensity score analysis the planned tandem autotransplant cohort had significantly lower treatment-related mortality (P = .044) but no different risk of relapse (P = .541) compared to the planned single transplant cohort. Tandem autotransplants for testicular cancer are associated with less treatment-related mortality than a planned single transplant, with no differences in disease-related outcomes or overall survival at 3 years. Patient selection bias for either transplant approach, however, may affect the results of this observational study; a randomized trial is needed to determine which approach, if either, is better.
Biology of Blood and Marrow Transplantation 08/2007; 13(7):778-89. · 3.87 Impact Factor
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Julie A Panepinto,
Mark C Walters, Jeanette Carreras,
Judith Marsh,
Christopher N Bredeson,
Robert Peter Gale,
Gregory A Hale,
John Horan,
Jill M Hows,
John P Klein,
Ricardo Pasquini,
Irene Roberts,
Keith Sullivan,
Mary Eapen,
Alina Ferster
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ABSTRACT: We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso-occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received >10 red blood cell transfusions before HCT. Twenty-seven percent of patients had a poor performance score at transplantation. Ninety-four percent received busulfan and cyclophosphamide-containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post-transplant period. Rates of acute and chronic graft-versus-host disease were 10% and 22% respectively. Sixty-four of 67 patients are alive with 5-year probabilities of disease-free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle-related events. This report confirms and extends earlier reports that HCT from HLA-matched related donors offers a very high survival rate, with few transplant-related complications and the elimination of sickle-related complications in the majority of patients who undergo this therapy.
British Journal of Haematology 06/2007; 137(5):479-85. · 4.94 Impact Factor
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John M Pagel,
Frederick R Appelbaum,
Janet F Eary,
Joseph Rajendran,
Darrell R Fisher,
Ted Gooley,
Katherine Ruffner,
Eneida Nemecek,
Eileen Sickle,
Larry Durack, Jeanette Carreras,
Mary M Horowitz,
Oliver W Press,
Ajay K Gopal,
Paul J Martin,
Irwin D Bernstein,
Dana C Matthews
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ABSTRACT: In an attempt to improve outcomes for patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT), we conducted a phase 1/2 study in which targeted irradiation delivered by 131I-anti-CD45 antibody was combined with targeted busulfan (BU; area-under-curve, 600-900 ng/mL) and cyclophosphamide (CY; 120 mg/kg). Fifty-two (88%) of 59 patients receiving a trace 131I-labeled dose of 0.5 mg/kg anti-CD45 murine antibody had higher estimated absorbed radiation in bone marrow and spleen than in any other organ. Forty-six patients were treated with 102 to 298 mCi (3774-11 026 MBq) 131I, delivering an estimated 5.3 to 19 (mean, 11.3) Gy to marrow, 17-72 (mean, 29.7) Gy to spleen, and 3.5 Gy (n = 4) to 5.25 Gy (n = 42) to the liver. The estimated 3-year nonrelapse mortality and disease-free survival (DFS) were 21% and 61%, respectively. These results were compared with those from 509 similar International Bone Marrow Transplant Registry patients who underwent transplantation using BU/CY alone. After adjusting for differences in age and cytogenetics risk, the hazard of mortality among all antibody-treated patients was 0.65 times that of the Registry patients (95% CI 0.39-1.08; P = .09). The addition of targeted hematopoietic irradiation to conventional BU/CY is feasible and well tolerated, and phase 2 results are sufficiently encouraging to warrant further study.
Blood 04/2006; 107(5):2184-91. · 9.90 Impact Factor
