scholarly journals Adult Recipients of Matched Related Donor Blood Cell Transplants Given Myeloablative Regimens Including Pretransplant Antithymocyte Globulin Have Lower Mortality Related to Graft-versus-Host Disease: A Matched Pair Analysis

2007 ◽  
Vol 13 (3) ◽  
pp. 299-306 ◽  
Author(s):  
James A. Russell ◽  
A. Robert Turner ◽  
Loree Larratt ◽  
Ahsan Chaudhry ◽  
Donald Morris ◽  
...  
Keyword(s):  
Blood Cell ◽  
Graft Versus Host Disease ◽  
Antithymocyte Globulin ◽  
Matched Pair ◽  
Donor Blood ◽  
Graft Versus Host ◽  
Matched Pair Analysis ◽  
Cell Transplants ◽  
Related Donor ◽  
Pair Analysis

Adult Recipients of Matched Related Donor Blood Cell Transplants (BCT) Given Pretransplant Low-Dose Antithymocyte Globulin (ATG) Have Less Chronic Graft-Versus-Host Disease (cGVHD) and Transplant-Related Mortality (TRM): A Matched Pair Analysis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2250-2250
Author(s):  
James A. Russell ◽  
A. Robert Turner ◽  
Loree Larratt ◽  
Ahsan M. Chaudhry ◽  
Oluyeme Jeje ◽  
...  
Keyword(s):  
Blood Cell ◽  
Graft Versus Host Disease ◽  
Antithymocyte Globulin ◽  
Progression Free Survival ◽  
Not Given ◽  
Free Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Related Donor ◽  
Related Mortality

Abstract Because pretransplant antithymocyte globulin (ATG) seems to reduce graft-versus-host disease (GVHD) and transplant-related mortality (TRM) after unrelated donor bone marrow transplant (BMT) we have investigated this agent in matched related donor (MRD) blood cell transplant (BCT). Of 82 adults receiving myeloablative conditioning and first MRD BCT between 01/99 and 05/02, 54 were matched for disease and stage with 54 patients (pts) not given ATG between 12/94 and 11/98. Median age was 42 (range 18 – 63) for ATG pts and 41 (range 22 – 54) for controls. Included in each group were 22 standard-risk pts (16 AML CR1, 6 ALL CR1), and 14 with high-risk acute leukemia of whom 12 had active AML (7 arising from MDS, 3 induction failures, 1 refractory, 1 relapse), and 2 ALL (1 refractory, 1 relapse). An additional 18 pts included 2 AML CR2, 1 ALL CR2, 2 CML AP/CP2, 2 MM, 8 relapsed/refractory NHL (2 mantle cell, 4 low, 1 intermediate, 1 high-grade) and 3 relapsed/refractory CLL. More control pts had conditioning incorporating TBI (32 vs 11, p<0.0001). All pts were given cyclosporine A and “short course” methotrexate with folinic acid. The study group received Thymoglobulin (Genzyme) (ATG) 4.5 mg/kg in divided doses over 3 consecutive days pretransplant finishing D0. ATG recipients were followed for 22 to 62 months (median 46) and control patients for 65–112 months (median 84). The actuarial incidence of acute GVHD grades II – IV was 25±6% in ATG recipients compared with 37±7% in the controls (p = ns). The figures for grade III – IV disease were 13±5% and 20±7% respectively (p = ns). Incidence of cGVHD at two years was 40±7% with ATG vs 97±3% without ATG (p < 0.0001), figures for extensive disease were 32±7% and 94±3% respectively (p < 0.0001). Sites of involvement by cGVHD were similar apart from gastrointestinal disease which was relatively more frequent in those ATG recipients who developed cGVHD (26% vs 5%, p = 0.03). Non-relapse mortality with and without ATG respectively was 4±3% vs 17±5% at 100 days and 9±4% vs 32±7% at 2 years (p = 0.004). Deaths were GVHD related in 3 ATG treated patients vs 13 controls (p=0.01). In the control group 2 year TRM was 26±8% in 32 TBI recipients compared with 42±11% in 22 patients not given TBI (p = ns). Relapse rate at 2 years was 36±7% for ATG recipients and 23±7% in controls (p = 0.06). Six of 21 relapsing patients in the ATG group survive having achieved another remission (4) or disease stabilization (2) after more treatment. One of 12 control patients who relapsed is currently alive in remission after a second BCT. Survival at 2 years was 70±6% in the patients given ATG vs. 54±7% in the controls (p=0.08) and progression-free survival was 57±7% vs 52±7% respectively. This study indicates that MRD BCT recipients given pretransplant ATG experience less cGVHD, less overall TRM and lower mortality related to both acute and chronic GVHD. These findings are not due to more control pts receiving TBI. Despite a trend to more relapse progression-free survival is unaffected, there is a trend to improved survival and presumably quality of life is generally better in ATG recipients because fewer of them have cGVHD.

Adult Recipients of Matched Related Donor Blood Cell Transplants Given Pretransplant Antithymocyte Globulin Have Less Graft-Versus-Host Disease and Transplant-Related Mortality: Follow-Up of a Matched Pair Analysis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2865-2865
Author(s):  
James A. Russell ◽  
Loree M. Larratt ◽  
A. Robert Turner ◽  
M. Ahsan Chaudhry ◽  
Oluyeme Jeje ◽  
...  
Keyword(s):  
Blood Cell ◽  
Antithymocyte Globulin ◽  
Chronic Gvhd ◽  
Immunosuppressive Treatment ◽  
Matched Pair ◽  
Control Group ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Related Donor ◽  
And Control

Abstract Because pretransplant antithymocyte globulin (ATG) seems to reduce GVHD and TRM after unrelated donor BMT we have investigated this agent in matched related donor (MRD) blood cell transplant (BCT). Fifty-four adults receiving rabbit ATG (Thymoglobulin, Genzyme), cyclosporine A (CSA) and methotrexate with a first MRD BCT were matched for disease and stage (AML 16 CR1, 2 CR2, 12 advanced, ALL 6 CR1, 1 CR2, 2 advanced, CML 1 AP, 1 CP2, CLL 3 rel/ref, NHL 8 rel/ref, MM 2 rel/ref) with 54 patients not given ATG. Myeloablative conditioning for ATG pts comprised fludarabine (Flu) 50 mg/m 2 x 5 with busulfan (Bu) 4mg/kg PO x 4 (7), Bu 3.2mg. kg IV x 4 (36) or Bu 3.2mg. kg IV x 4 plus TBI 200cGy x 2 (10) and VP16 60mg/kg + TBI 1200cGy (1). Controls were given VP16 60mg/kg + TBI 1200cGy (26) or 500cGy (2), TBI 1200cGy + Cyclophosphamide (Cy) 120mg/kg (2) or Cy 180mg/kg (2), Bu 4mg/kg PO x 4 + Cy 120mg/kg and Bu 4mg/kg PO x 4 + Flu 50 mg/m 2 x 5. The ATG was given at a total dose of 4.5 mg/kg over 3 days finishing day 0. Surviving ATG recipients were followed for 49 to 89 months (median 72) and control pts for 90–137 months (median 110). Rates of acute GVHD (aGVHD) grade II–IV, aGVHD grade III–IV, chronic GVHD (cGVHD) and extensive cGVHD were 15±5% vs. 32±6% (p=0.036), 6±3% vs. 13±5% (p = ns), 67±7% vs. 97±3% (p = 0.035) and 50±7%vs. 95±5% (p = 0.005) in the ATG and control groups respectively. Patients given ATG had fewer sites of involvement by cGVHD than the control group (mean 1.87±0.22 vs 2.72±0.24, p = 0.013). Those ATG pts with cGVHD were treated for a median of 382 days compared with 473 for controls (p = ns). Of 46 ATG recipients with grade 0 - I aGVHD 41 lived beyond 105 days. Twenty-five discontinued CSA at 44 – 890 days (median 75) and 16 developed cGVHD while still on CSA. Of 37 control patients with grade 0 - I aGVHD 31 lived beyond 105 days, 8 stopped CSA at 62 – 145 days (median 110) and 21 developed cGVHD while still taking CSA. Of 35 ATG recipients alive beyond 4 years 11 had never received immunosuppressive treatment for cGVHD compared with one of 27 controls (p = 0.008). Non-relapse mortality with and without ATG respectively was 4±3% vs 17±5% at 100 days and 9±4% vs 34±7% at 4 years (p = 0.002). Three of 9 pts given oral Bu with Flu died of transplant-related causes. Deaths were GVHD related in 3 ATG treated patients vs 14 controls (p=0.007). Despite a trend to more relapse with ATG (43±7% vs. 22±7% at 4 years, p = 0.053) survival was 66±7% in the patients given ATG vs 50±7% in the controls (p=0.046). This study indicates that MRD BCT recipients given regimens including Flu, oral or IV Bu and ATG experience less cGVHD, lower mortality related to both acute and cGVHD and probably improved quality of life in survivors compared with previous protocols. It is unlikely that substituting Flu for Cy with Bu or differences in CSA taper contributed to the improved results but it is possible that IV Bu may have done so to some extent. Attempts to improve outcomes further will need to address the problem of relapse.

Antithymocyte Globulin (ATG), Cyclosporine (CyA), and Danazol Versus ATG and CyA As Treatment for Children with Aplastic Anemia: Result of Matched-Pair Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2400-2400
Author(s):  
Kazuko Kudo ◽  
Ryoji Kobayashi ◽  
Yoshiyuki Kosaka ◽  
Masahiro Tsuchida ◽  
Hideo Mugishima ◽  
...  
Keyword(s):  
Overall Survival ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Response Rate ◽  
Clonal Evolution ◽  
Survival Rates ◽  
Matched Pair ◽  
Free Survival ◽  
Matched Pair Analysis ◽  
Pair Analysis

Abstract Abstract 2400 Introduction: Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) plus cyclosporine A (CyA) has been the standard therapy for aplastic anemia (AA) patients. Recently, telomerase shortening was observed in constitutional marrow failure and some acquired AA patients. In addition, constitutional marrow failure syndrome of variable severity may be present in otherwise phenotypically normal individuals and can masquerade as acquired AA. Calado et al. reported that androgens increased telomerase activity in vitro. The addition of androgens to immunosuppressive therapy may increase the response rate by the effect for these hidden patients. Because all patients in the AA-92 study received danazol and patients in AA 97 study did not receive danazol, we have a unique chance to evaluate the effects of androgen. In this report we present results comparing AA-92 (ATG+CyA+danazol) with AA-97 (ATG+CyA) protocol for children with AA using a matched-pair analysis. Patients and Methods: We conducted two prospective multicenter studies: the AA-92 and AA-97, which began in November 1992 and October 1997, respectively. From 1992 to 2009, 530 children with AA were treated with IST. IST consisted of horse ATG (15 mg/kg/day, days 1 to 5), CyA (6 mg/kg/day, days 1 to 180) and methylprednisolone. All patients in the AA-92 study received danazol at a dose of 5 mg/kg/day for 6 months. We selected pairs of patients treated with either AA-92 or AA-97 by matching the variables of disease severity, age, sex, and duration from diagnosis to IST. We assessed hematologic response at 3 and 6 months after initiation of therapy as well as overall survival and failure-free survival. Definition of treatment failure was death, relapse, disease progression requiring stem cell transplantation or second IST, and clonal evolution. Results: Among 530 patients, 104 pairs were matched and their disease severity was very severe (VSAA) (n=43), severe (SAA) (n=34), and non-severe (NSAA) (n=27). Median age was 8 years (1–15) and 53 (51.0%) were male. In the AA-92 study, the response rates at 3 and 6 months were 48/104 (46.2%) and 71/104 (68.3%), respectively. In the AA-97 study, the response rates at 3 and 6 months were 49/103 (47.6%) and 59/104 (56.7%), respectively. The overall 10-year survival rates in AA-92 and AA-97 were 82.7% and 93.6%, respectively. In VSAA patients, the response rate at 6 months in AA-92 was significantly higher than in AA-97 (69.8% vs 46.5%, p=0.029). However, the overall 10-year survival rates for patients with VSAA in AA-92 and AA-97 were 81.4% and 90.4%, respectively. The failure-free 7-year survival rates for patients with VSAA in AA-92 and AA-97 were 55.5% and 61.5%, respectively. The cumulative incidence of clonal evolution between studies did not differ. Conclusions: Our results showed that the response rate of VSAA patients at 6 months in the danazol group was significantly higher than in those not receiving danazol, but overall survival and failure-free survival were not different. There is a possibility that a number of cases with androgen-responsive congenital bone marrow failure syndrome, such as dyskeratosis congenita, were hidden in our series of AA patients, which may explain the higher response rate with danazol in AA-92. Disclosures: No relevant conflicts of interest to declare.

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