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O Ringdén,
S Shrestha,
G T da Silva,
M-J Zhang,
A Dispenzieri,
M Remberger,
R Kamble,
C O Freytes,
R P Gale, J Gibson,
V Gupta,
L Holmberg,
H Lazarus,
P McCarthy,
K Meehan,
H Schouten,
G A Milone,
S Lonial,
P N Hari
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ABSTRACT: We evaluated the effect of acute and chronic GVHD on relapse and survival after allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005, following NMA (n=98) or RIC (n=79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (aGVHD; grades I-IV) was 42% (95% confidence interval (CI), 35-49%) and of chronic GVHD (cGVHD) at 5 years was 59% (95% CI, 49-69%), with 70% developing extensive cGVHD. In multivariate analysis, aGVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42, P=0.016), whereas limited cGVHD significantly decreased the risk of myeloma relapse (RR=0.35, P=0.035) and was associated with superior EFS (RR=0.40, P=0.027). aGVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52, P=0.001). The reduction in relapse risk associated with cGVHD is consistent with a beneficial graft-vs-myeloma effect, but this did not translate into a survival advantage.
Bone marrow transplantation 09/2011; 47(6):831-7. · 3.00 Impact Factor
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Parameswaran N Hari,
Navneet S Majhail,
Mei-Jie Zhang,
Anna Hassebroek,
Fareeha Siddiqui,
Karen Ballen,
Asad Bashey,
Jenny Bird,
Cesar O Freytes, John Gibson, [......],
Nancy Omondi,
Donna E Reece,
Matthew Seftel,
Michael Trigg,
David Vesole,
Brendan Weiss,
Peter Wiernik,
Stephanie J Lee,
J Douglas Rizzo,
Paulette Mehta
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ABSTRACT: Blacks are twice as likely to develop and die from multiple myeloma (MM), and are less likely to receive an autologous hematopoietic-cell transplant (AHCT) for MM compared to Whites. The influence of race on outcomes of AHCT for MM is not well described. We compared the probability of overall survival (OS), progression-free survival (PFS), disease progression, and nonrelapse mortality (NRM) among Black (N=303) and White (N=1892) recipients of AHCT for MM, who were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2005. The Black cohort was more likely to be female, and had better Karnofsky performance scores, but lower hemoglobin and albumin levels at diagnosis. Black recipients were younger and more likely to be transplanted later in their disease course. Disease stage and treatment characteristics prior to AHCT were similar between the 2 groups. Black and White recipients had similar probabilities of 5-year OS (52% versus 47%, P=.19) and PFS (19% versus 21%, P=.64) as well as cumulative incidences of disease progression (72% versus 72%, P=.97) and NRM (9% versus 8%, P=.52). In multivariate analyses, race was not associated with any of these endpoints. Black recipients of AHCT for MM have similar outcomes compared to Whites, suggesting that the reasons underlying lower rates of AHCT in Blacks need to be studied further to ensure equal access to effective therapy.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2009; 16(3):395-402. · 3.15 Impact Factor
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P N Hari,
M-J Zhang,
V Roy,
W S Pérez,
A Bashey,
L B To,
G Elfenbein,
C O Freytes,
R P Gale, J Gibson,
R A Kyle,
H M Lazarus,
P L McCarthy,
G A Milone,
S Pavlovsky,
D E Reece,
G Schiller,
J Vela-Ojeda,
D Weisdorf,
D Vesole
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ABSTRACT: The international staging system (ISS) for multiple myeloma (MM) is a validated alternative to the Durie-Salmon staging system (DSS) for predicting survival at diagnosis. We compared these staging systems for predicting outcomes after upfront autologous stem cell transplantation by analyzing the outcomes of 729 patients between 1995 and 2002. With a median follow-up of 56 months, the univariate probabilities (95% CI) of non-relapse mortality (NRM), relapse, progression-free survival (PFS) and overall survival (OS) at 5 years were 7, 68, 25 and 52%, respectively. The median OS for stages I, II, III by DSS and ISS were 82, 68, 50 and 64, 68, 45 months, respectively. The concordance between the two staging systems was only 36%. Staging systems were formally compared using Cox models fit with DSS and ISS stages. The relative risks of PFS and OS were significantly different for stages I vs II and II vs III for DSS, but only for stages II vs III for ISS. Although both systems were predictive of PFS and OS, the DSS was superior in formal statistical comparison using Brier score. However, neither system was strongly predictive of outcomes, indicating the need for newer schemes incorporating other prognostic markers.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 04/2009; 23(8):1528-34. · 8.30 Impact Factor
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D E Reece,
C Bredeson,
W S Pérez,
S Jagannath,
M J Zhang,
K K Ballen,
G J Elfenbein,
C O Freytes,
R P Gale,
M A Gertz, [......],
D Marcellus,
P L McCarthy,
G A Milone,
S D Nimer,
S Pavlovsky,
L B To,
D J Weisdorf,
P H Wiernik,
J R Wingard,
D H Vesole
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ABSTRACT: The role of autologous stem cell transplantation (AuSCT) in older multiple myeloma patients is unclear. Using data from the Autologous Blood and Marrow Transplant Registry, we compared the outcome of 110 patients >/=the age of 60 (median 63; range 60-73) years, undergoing AuSCT with that of 382 patients <60 (median 52; range 30-59) years. The two groups were similar except that older patients had a higher beta(2)-microglobulin level at diagnosis (P=0.016) and fewer had lytic lesions (P=0.007). Day 100 mortality was 6% (95% confidence interval 4-9) and 1-year treatment-related mortality (TRM) was 9% (6-13) in patients <60 years, compared with 5% (2-10) and 8% (4-14), respectively, in patients >/=60 years. The relapse rate, progression-free survival (PFS) and overall survival (OS) in the two groups were also similar. Multivariate analysis of all patients identified only an interval from diagnosis to AuSCT >12 months and the use of two prior chemotherapy regimens within 6 months of AuSCT as adverse prognostic factors. Our results indicate that AuSCT can be safely performed in selected older patients: the best results were observed in patients undergoing AuSCT relatively early in their disease course.
Bone Marrow Transplantation 12/2003; 32(12):1135-43. · 3.75 Impact Factor
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H M Lazarus,
F R Loberiza,
M J Zhang,
J O Armitage,
K K Ballen,
A Bashey,
B J Bolwell,
L J Burns,
C O Freytes,
R P Gale, [......],
D Marks,
J Mason,
A M Miller,
G A Milone,
S Pavlovsky,
D E Reece,
J D Rizzo,
K van Besien,
J M Vose,
M M Horowitz
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ABSTRACT: Although patients with relapsed Hodgkin's disease have a poor prognosis with conventional therapies, high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autotransplantation) may provide long-term progression-free survival. We reviewed data from the Autologous Blood and Marrow Transplant Registry (ABMTR) to determine relapse, disease-free survival, overall survival, and prognostic factors in this group of patients. Detailed records from the ABMTR on 414 patients with Hodgkin's disease in first relapse (n = 295) or second complete remission (CR) (n = 119) receiving an autotransplant from 1989 to 1995 were reviewed. Median age was 29 (range, 7-64) years. Median time from diagnosis to relapse was 18 (range, 6-219) months; median time from relapse to transplant was 5 (range, <1-215) months. Most patients received high-dose chemotherapy without total body irradiation for conditioning (n = 370). The most frequently used high-dose regimen was cyclophosphamide, BCNU, VP-16 (CBV) (n = 240). The graft consisted of bone marrow (n = 246), blood stem cells (n = 112), or both (n = 56). Median follow-up was 46 (range, 5-96) months. One hundred-day mortality (95% confidence interval) was 7 (5-9)%. One hundred and sixty-five of 295 patients (56%) transplanted in relapse achieved CR after autotransplantation. Of these, 61 (37%) recurred. Twenty-four of 119 patients (20%) transplanted in CR recurred. The probability of disease-free survival at 3 years was 46 (40-52)% for transplants in first relapse and 64 (53-72)% for those in second remission (P < 0.001). Overall survival at 3 years was 58 (52-64)% after transplantation in first relapse and 75 (66-83)% after transplantation in second CR (P < 0.001). In multivariate analysis, Karnofsky performance score <90% at transplant, abnormal serum LDH at transplant, and chemotherapy resistance were adverse prognostic factors for outcome. Progression of Hodgkin's disease accounted for 69% of all deaths. Autotransplantation should be considered for patients with Hodgkin's disease in first relapse or second remission. Future investigations should focus on strategies designed to decrease relapse after autotransplantation, particularly in patients at high risk for relapse.
Bone Marrow Transplantation 02/2001; 27(4):387-96. · 3.75 Impact Factor
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[show abstract]
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ABSTRACT: Aplastic anemia is caused by several diverse factors, including a lack of or defective hematopoietic stem cells, immune abnormalities, and disorders of the bone marrow microenvironment. The outcome of transplanting bone marrow from genetically identical twins into patients with aplastic anemia may help define how frequently these factors play a role in this condition.
To determine the outcome of transplanting bone marrow from genetically identical twins into patients with aplastic anemia.
Observational study.
31 centers participating in the international Bone Marrow Transplant Registry.
40 patients with aplastic anemia who received bone marrow transplants from their genetically identical twins between 1964 and 1992.
23 patients received their first bone marrow transplant without pretransplantation conditioning; 17 received it after pretransplantation conditioning with cyclophosphamide alone or combined with other drugs or radiation. Six patients received post-transplantation immunosuppressive therapy with methotrexate, cyclosporine, and corticosteroids, alone or in combination.
Outcomes of transplantation, including hematologic recovery and survival.
Seven of 23 patients who received their first transplant without receiving conditioning had sustained complete hematologic recovery. One of 16 patients who did not have complete recovery after the first transplantation recovered after a second transplantation, which was not preceded by conditioning. The other 15 patients had two to five transplantations that were preceded by conditioning; in 13 patients, sustained bone marrow function was recovered. Twelve of 17 patients whose first transplantation was preceded by conditioning had sustained complete hematologic recovery. The likelihood of hematologic recovery was greater in patients who had conditioning before the first transplantation (P = 0.033). The actuarial 10-year survival rate for the 40 patients was 78% (95% CI, 59% to 92%). The survival rate was higher in patients who did not have conditioning before the first transplantation (patients without conditioning, 87% [range, 65% to 99%]; patients with conditioning, 70% [range, 47% to 89%]; P = 0.037).
Most patients with aplastic anemia recover bone marrow function after receiving a transplant from a genetically identical twin. Pretransplantation conditioning may increase the chance of bone marrow recovery but does not seem to improve survival.
Annals of internal medicine 02/1997; 126(2):116-22. · 16.73 Impact Factor
