Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO)

Blood ◽  
2001 ◽  
Vol 98 (10) ◽  
pp. 2942-2947 ◽  
Author(s):  
Andrea Bacigalupo ◽  
Teresa Lamparelli ◽  
Paolo Bruzzi ◽  
Stefano Guidi ◽  
Paolo Emilio Alessandrino ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Antithymocyte Globulin ◽  
Advanced Disease ◽  
Chronic Gvhd ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Unrelated Donors ◽  
To Receive ◽  
Grade Iii

Abstract One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n = 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n = 29) ; (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n = 28) versus 15 mg/kg rabbit ATG (n = 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P = .8) in the first and in 50% versus 11% (P = .001) in the second trial. Transplant-related mortality (TRM), relapse, and actuarial 3-year survival rates were comparable in both trials. In fact, despite the reduction of GVHD in the second trial, a higher risk for lethal infections (30% vs 7%; P = .02) was seen in the arm given 15 mg/kg ATG. Extensive chronic GVHD developed overall more frequently in patients given no ATG (62% vs 39%;P = .04), as confirmed by multivariate analysis (P = .03). Time to 50 × 109/L platelets was comparable in the first trial (21 vs 24 days; P = .3) and delayed in the ATG arm in the second trial (23 vs 38 days;P = .02). These trials suggest that (1) 15 mg/kg ATG before BMT significantly reduces the risk for grade III-IV acute GVHD, (2) this does not translate to a reduction in TRM because of the increased risk for infections, and (3) though survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG.

Increased risk of extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation using unrelated donors

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 548-551 ◽  
Author(s):  
Mats Remberger ◽  
Dietrich W. Beelen ◽  
Axel Fauser ◽  
Nadezda Basara ◽  
Oliver Basu ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Unrelated Donors

AbstractThe long-term follow-up of a study including 214 patients receiving either peripheral blood stem cells (PBSCs) or bone marrow (BM) from an HLA-A, -B, and -DR–compatible unrelated donor is presented. Median follow-up was 4.4 (2.3-7.3) and 5.0 (0.7-8.4) years in the 2 groups, respectively. Cumulative incidence of overall chronic graft-versus-host disease (GVHD) was similar in the 2 groups (78% vs 71%), while extensive chronic GVHD was significantly more common in the PBSC group compared with the BM group (39% vs 24%, P = .03). The 5-year transplant-related mortality (TRM) was 37% in the PBSC group and 35% in the BM controls (P = .7), and overall survival was 42% in both groups. The relapse incidences were 26% and 27% in the 2 groups, respectively, resulting in a disease-free survival of 41% in both groups. In conclusion, PBSCs from HLA-compatible unrelated donors results in similar outcome compared to BM but implies an increased risk for extensive chronic GVHD.

Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3683-3686 ◽  
Author(s):  
Samar Kulkarni ◽  
Ray Powles ◽  
Jennie Treleaven ◽  
Unell Riley ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Pneumococcal Infection ◽  
Pneumococcal Infections ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Penicillin Prophylaxis

Abstract Incidences of and risk factors for Streptococcus pneumoniaesepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997. SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months). The infection was fatal in 7 patients. The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively. Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS. Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P = .03) and chronic GVHD (10-year probability, 14% vs 4%; P = .002) were associated with significantly higher risk for SPS. All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127;P = .07). Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis. None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus. Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16;P = .04). We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD. Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk. These patients should receive lifelong pneumococcus prophylaxis. Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections. Further studies are required to determine the optimum prophylactic strategy in patients at risk.

scholarly journals Adverse events in second- and third-line treatments for acute and chronic graft-versus-host disease: systematic review

2020 ◽  
Vol 11 ◽  
pp. 204062072097703
Author(s):  
Vladica M. Velickovic ◽  
Emily McIlwaine ◽  
Rongrong Zhang ◽  
Tim Spelman
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Pharmaceutical Management ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Third Line

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased risk of graft- versus-host disease (GvHD), a strong prognostic predictor of early mortality within the first 2 years following allo-HSCT. The objective of this study was to describe the harm outcomes reported among patients receiving second- and third-line treatment as part of the management for GvHD via a systematic literature review. Methods: A total of 34 studies met the systematic review inclusion criteria, reporting adverse events (AEs) across 12 different second- and third-line therapies. Results: A total of 14 studies reported AEs across nine different therapies used in the treatment of acute GvHD (aGvHD), 17 studies reported AEs of eight different treatments for chronic GvHD (cGvHD) and 3 reported a mixed population. Infections were the AE reported most widely, followed by haematologic events and laboratory abnormalities. Reported infections per patient were lower under extracorporeal photopheresis (ECP) for aGvHD (0.267 infections per patient over 6 months) relative to any of the therapies studied (ranging from 0.853 infections per patient per 6 months under etanercept up to 1.998 infections per patient on inolimomab). Conclusion: The reported incidence of infectious AEs in aGvHD and grade 3–5 AEs in cGvHD was lower on ECP compared with pharmaceutical management.

Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3683-3686 ◽  
Author(s):  
Samar Kulkarni ◽  
Ray Powles ◽  
Jennie Treleaven ◽  
Unell Riley ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Pneumococcal Infection ◽  
Pneumococcal Infections ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Penicillin Prophylaxis

Incidences of and risk factors for Streptococcus pneumoniaesepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997. SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months). The infection was fatal in 7 patients. The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively. Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS. Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P = .03) and chronic GVHD (10-year probability, 14% vs 4%; P = .002) were associated with significantly higher risk for SPS. All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127;P = .07). Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis. None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus. Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16;P = .04). We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD. Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk. These patients should receive lifelong pneumococcus prophylaxis. Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections. Further studies are required to determine the optimum prophylactic strategy in patients at risk.

scholarly journals Final Results of a Multicenter Prospective Phase II Trial of Allogeneic Transplantation for Relapsed/Refractory CD20+ B-Cell Lymphomas: Effect of Rituximab on Graft-Versus-Host Disease-Free/Relapse-Free Survival (GRFS)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3473-3473
Author(s):  
Anna Dodero ◽  
Francesca Patriarca ◽  
Giuseppe Milone ◽  
Barbara Sarina ◽  
Rosalba Miceli ◽  
...  
Keyword(s):  
B Cell ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
High Dose ◽  
B Cell Lymphomas ◽  
Host Disease ◽  
Graft Versus Host ◽  
Prospective Phase ◽  
Unrelated Donors

Abstract Introduction: Patients with refractory and relapsed B-cell lymphomas have few curative options. Despite novel target therapies, only patients receiving allogeneic stem cell transplantation (alloSCT) can achieve a long-term disease control. A lot of effort has been done over the last years to produce strategies reducing non-relapse mortality (NRM) without damaging the graft-versus-lymphoma effect. We conducted a multicenter prospective phase II trial to evaluate the benefit of high-dose Rituximab (R) in the conditioning regimen before alloSCT. The primary end-point of the study was progression-free (PFS) survival. We evaluated also the long-term outcome with the novel composite end-point of graft-versus-host disease-free/relapse-free survival (GRFS). Methods:The study enrolled 121 adult patients who received alloSCT for relapsed/refractory B-cell lymphomas [n=35 (28%) follicular lymphomas; n=29 (24%) chronic-lymphocytic leukemia; n=35 (28%) diffuse large B-cell lymphomas; n= 22 (18%) mantle cell lymphomas]. The median age was 52 years (range, 23-65). Seventy-four pts (61%) failed a previous autograft. The conditioning regimen consisted of thiotepa (12 mg/kg), cyclophosphamide (60 mg/kg) and fludarabine (60 mg/m2) and high-dose of rituximab (500 mg/m2 on day-6),. Graft-versus-host disease (GVHD) prophylaxis was based on cyclosporine and mini-methotrexate; ATG (7 mg/kg) was given to the patients allografted from unrelated donors. Sixty-seven (55%) and fifty-four (45%) patients received grafts from related and unrelated donors, respectively. Results: At a median follow-up of 41 months (range 6-95 months), the estimated 3-years PFS and overall survival (OS) were 50% (95%CI, 41%-61%) and 61% (95%CI, 51%-71%), respectively. The 1 and 3-years GRFS were 40% (95%CI, 32%-50%) and 34% (95%CI, 26%-44%), respectively. The GRFS was significantly better in patients affected by indolent disease (43% versus 22%, long-rank test, p=0.02); in addition there was a tendency for better GRFS for those transplanted from unrelated donors (41% versus 27%, p=0.096). The 3-years GRFS were 41% and 30% in patients with complete remission (CR) and partial remission (PR) at the time of transplant, respectively (p=0.185). The multivariate analysis showed that patients affected by aggressive histotype and with bone marrow (BM) infiltration at time of transplant had a poor outcome in terms of PFS, OS and GRFS [hystotype: PFS, HR 3.30 (p=0.003); OS, HR 3.73 (p=0.007); GRFS, HR 2.02 (p=0.026); BM infiltration: PFS, HR 4.79 (p<0.001); OS, HR 6.00 (p<0.001); GRFS, HR 2.7 (p=0.004)]. The crude cumulative incidence (CCI) of NRM was 21% (95%CI, 14%-30%) at 3-years whereas the CCI of acute GVHD grade II-IV was 22% (95%CI,15%-30%). The CCI of acute GVHD was not statistically significant different in matched sibling donors and unrelated donors (21% versus 22%, respectively p=0.717). According to the modified Seattle criteria, the CCI of extensive GVHD was 17% (95%CI, 11%-27%) whereas the limited form was 27% (95%CI, 19%-39%). In the univariable Fine and Gray model, the only factor that was protective against the occurrence of chronic GVHD was the transplant from unrelated donors when R and ATG were combined together [HR 0.50 (95%CI, 0.25-0.99), p=0.05]. In fact, the CCI of chronic GVHD at 3-years from matched sibling donors was 54% (95%CI,42%-71%) as opposed to 31% from unrelated donors (95%CI, 19%-49%) (p=0.04). Conclusions: Our trial showed:1) R did not improve PFS as compared with our historical control; 2) the combination of R and ATG is synergistic and resulted protective against chronic GVHD; 3) GRFS analysis showed that 34% of the patients are alive without any complications at 3-years after allograft and this should be the standard to compare novel drug results. Future protocols should consider the use of GRFS as endpoint and inclusion of ATG also for those receiving sibling grafts. Disclosures Cascavilla: Janssen-Cilag: Honoraria.

Prognostic Relevance of “Early-Onset” Graft-Versus-Host Disease Following Nonmyeloablative Hematopoietic Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 423-423
Author(s):  
Marco Mielcarek ◽  
Lauri Burroughs ◽  
Wendy Leisenring ◽  
Paul Martin ◽  
Razvan Diaconezcu ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Early Onset ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Host Disease ◽  
Graft Versus Host ◽  
Unrelated Donors

Abstract We have shown that graft-versus-host disease (GVHD) after nonmyeloablative hematopoietic cell transplantation (HCT) occurs a median of 2 months later than after myeloablative HCT (Blood 102:756, 2003). Here, we asked whether there was an association between the time of onset of GVHD and survival after nonablative HCT. We retrospectively analyzed outcomes among 395 patients with hematologic diseases who had nonmyeloablative HCT from HLA-matched related (n=297) or unrelated donors (n=98). The nonablative regimen consisted of 2 Gy total body irradiation with or without fludarabine followed by postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. The cumulative incidences of grades II-IV acute GVHD and extensive chronic GVHD were 45% and 47%, respectively, with grafts from related donors, and 68% and 68%, respectively, with those from unrelated donors. The median time to prednisone initiation, a marker for the onset of both acute and chronic GVHD, was 79 (range, 8–799) days among patients with sibling donors and 28 (range, 5–104) days among patients with unrelated donors. Among patients with GVHD following related grafts (n=187), the cumulative incidence of non-relapse mortality (NRM) at 4 years was 55% among the tertile of patients who initiated prednisone before day 50 (“early initiation”), and 29% when prednisone was initiated on or after day 50 (“late initiation”; p&lt;0.001). After controlling for patient age, diagnosis, type of preparative regimen, number of previous chemotherapies and donor/recipient gender combinations in multivariate analysis, early initiation of prednisone was identified as an independent predictor of increased NRM (Table). The presence of comorbidid conditions at the time of transplant (Charlson Comorbidity Index &gt;=1) was neither predictive for the time of onset nor the overall incidence of GVHD. Among patients who initiated prednisone for the treatment of GVHD, those with pretransplant comorbidities had a significantly greater hazard of NRM than those without comorbidities (hazard ratio, 2.6; 95% confidence interval, 1.2–5.4; p=0.01). There was no association between time to prednisone initiation and survival after nonmyeloablative HCT from unrelated donors. In conclusion, early-onset GVHD (prednisone initiation before day 50) was associated with increased NRM and poor survival after nonmyeloablative HCT from HLA-identical related donors and identified a subgroup of patients who might benefit from more aggressive primary therapy of GVHD. Hazard of Non-Relapse Mortality According to Time to Prednisone Initiation (HLA-Matched Related Transplants) Prednisone Initiation for Treatment of GVHD [Day] Hazard Ratio† 95% Confidence Interval P* P** †Cox proportional hazards model treating “early vs. late prednisone initiation” as a time-dependent covariate; *compared to “not initiated”; **comparison of prednisone initiation &lt;day 50 vs.≥day 50 Not initiated 1.0 --- --- --- &lt;50 11.4 5.3–24.4 &lt;0.001 --- ≥50 6.3 2.8–14.5 &lt;0.001 0.04

Effect Analysis of Antithymocyte Globulin Versus Antilymphocyte Globulin for Graft Versus Host Disease Prophylaxis in 102 Cases of Allogeneic Hematopoitic Stem Cell.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4325-4325
Author(s):  
Chengcheng Fu ◽  
Shiqiang Qu ◽  
Wu Depei ◽  
Aining Sun ◽  
Zhengming Jin ◽  
...  
Keyword(s):  
Allergic Reaction ◽  
Graft Versus Host Disease ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cell Counts ◽  
Gvhd Prophylaxis ◽  
Increased Risk ◽  
Preparative Regimen

Abstract Abstract 4325 Objective Retrospective analysis the therapeutic and side effect of the rabbit antithymocyte (ATG) versus swine ALG within the preparative regimen of allogeneic hematopoietic transplantation (allo-HSCT) for graft versus host disease (GVHD) prophylaxis. Methods Totally 102 patients who had admitted to our hospital and been treated by allo-HSCT with the preparative regimen including ATG/ALG were followed up from June 2002 to June 2008. They were divided into ATG group and ALG group. The allergic reaction, effect of GVHD prophylaxis, transplantation related mortality (TRM), disease free survival (DFS) and relapse rate (RR) of these groups were retrospectively analyzed. Cumulative rate were analyzed by the Kaplan-Meier method and the factors associated with the III?‘‡W AGVHD were analyzed with the COX regression model. Results ALG group had more allergic reaction than ATG, but ATG group had more bacteremia and cytomegalovirus (CMV) antigenaemia. The haematopoiesis reconstitution was comparable in two groups. The III?‘‡W AGVHD, two-year TRM,DFS and RR were (40% vs 21%,p=0.028),(54% vs 29%,p=0.039),(41% vs 53%,p=0.174),(10% vs 24%,p=0.306),respectively in ATG/ALG groups. In multivariate analysis,10mg/kg ATG as a protective variable to III?‘‡W AGVHD occurrence(RR=0.53 ;95%CI, 0.38?‘0.71),The CD3+ cell counts of administration was associated with an increased risk for III?‘‡W GVHD(RR=4.43 ;95%CI, 3.87?‘4.95). Conclusion 10mg/kg ATG significantly decreased the risks for III?‘‡W AGVHD and extensive chronic GVHD(ecGVHD); The lethal infections became the most important cause of death in the ATG group, but the increased risk for infection did not neutralize the reduction of TRM induced by the decrease of severe GVHD. Disclosures: No relevant conflicts of interest to declare.

Administration of cyclosporine for 24 months compared with 6 months for prevention of chronic graft-versus-host disease: a prospective randomized clinical trial

Blood ◽  
2001 ◽  
Vol 98 (13) ◽  
pp. 3868-3870 ◽  
Author(s):  
Emin Kansu ◽  
Ted Gooley ◽  
Mary E. D. Flowers ◽  
Claudio Anasetti ◽  
H. Joachim Deeg ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Clinical Manifestations ◽  
Disease Free Survival ◽  
Free Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Alternative Donor ◽  
To Receive ◽  
Related Mortality

Abstract This study compared the incidence of clinical extensive chronic graft-versus-host disease (GVHD), transplantation-related mortality, survival, and relapse-free survival among recipients randomly assigned to receive a 24-month or a 6-month course of cyclosporine prophylaxis after transplantation of allogeneic marrow from an HLA-identical sibling or alternative donor. Patients who did not have clinical manifestations of chronic GVHD on day 80 after transplantation were eligible for the study if they previously had acute GVHD or if a skin biopsy showed histologic evidence of chronic GVHD. Clinical extensive chronic GVHD developed in 35 of the 89 patients (39%) in the 24-month group and 37 of the 73 patients (51%) in the 6-month group. The hazard of developing chronic GVHD was not significantly different in the 2 groups (hazard ratio = 0.76; 95% confidence interval, 0.48-1.21; P = .25). In addition, there were no significant differences between the 2 groups in transplantation-related mortality, survival, or disease-free survival.

scholarly journals Tacrolimus and minidose methotrexate for prevention of acute graft- versus-host disease after matched unrelated donor marrow transplantation

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4383-4389 ◽  
Author(s):  
D Przepiorka ◽  
C Ippoliti ◽  
I Khouri ◽  
M Woo ◽  
R Mehra ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Advanced Disease ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Unrelated Donors ◽  
Acute Graft

Abstract Thirty adults with leukemia or lymphoma undergoing marrow transplantation from HLA-compatible unrelated donors received tacrolimus (FK506), a new immunosuppressive macrolide lactone, and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 36 years (range 21 to 49 years). Twenty-four patients had advanced disease, and 11 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/d intravenously (i.v.) by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6, and 11. All patients engrafted. Grades 2–4 GVHD occurred in 34% (95% CI, 17% to 52%), and grades 3–4 GVHD in 17% (95% CI, 3% to 31%). Mild renal toxicity was common before day 100; 63% of patients had a doubling of creatinine, and 52% had a peak creatinine greater than 2 mg/dL, but only one patient was dialyzed. The median last i.v. dose of tacrolimus was 53% of the scheduled dose, and the median oral dose on day 100 was 41% of that scheduled. Overall survival at 1 year was 47% (95% CI, 27% to 66%). We conclude that tacrolimus can be combined safely with minidose methotrexate, and the combination has substantial activity in preventing acute GVHD after unrelated donor marrow transplantation.

scholarly journals Recovery of antibody production in human allogeneic marrow graft recipients: influence of time posttransplantation, the presence or absence of chronic graft-versus-host disease, and antithymocyte globulin treatment

Blood ◽  
1981 ◽  
Vol 58 (2) ◽  
pp. 360-368 ◽  
Author(s):  
RP Witherspoon ◽  
R Storb ◽  
HD Ochs ◽  
N Fluornoy ◽  
KJ Kopecky ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Antithymocyte Globulin ◽  
Hematologic Malignancy ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Antibody Responses ◽  
Secondary Response ◽  
Significant Information ◽  
Host Disease ◽  
Graft Versus Host

Abstract One-hundred fifty-three recipients of HLA-identical sibling marrow transplants for aplastic anemia or hematologic malignancy were injected with bacteriophage phi X174 (phage), pneumococcal polysaccharide antigen (PPA), or keyhole limpet hemocyanin (KLH). Antibody levels were determined several times in the 6 wk after injection. Multiple regression techniques were used to determine what factors played significant roles in the antibody response. The most significant factors were the time elapsed from transplantation, chronic graft- versus-host disease (GVHD), and antithymocyte globulin (ATG) treatment. All patients had low antibody responses to all antigens in the first 180 days from transplant. Beyond 180 days patients without chronic GVHD showed antibody responses indistinguishable from those of normal donors. However, patients with chronic GVHD had the following impairments: (1) primary response to phage, (2) conversion from IgM to IgG in secondary response to phage, (3) secondary response to KLH, and (4) response to PPA. ATG treatment given to patients either prophylactically or therapeutically for acute GVHD was followed by lower primary responses to phage in the first 180 days and poor ability to switch from IgM to IgG antibody in the secondary response beyond 180 days postgrafting. Other factors did not yield additional significant information about ability to predict antibody responses including diagnosis, conditioning regimen, treatment in or out of laminar air flow rooms, transplantation, pretransplant refractoriness of the recipient to platelet transfusions from random donors, donor age or donor sex, and steroid administration for treatment for prevention of GVHD. The data indicate that, given enough time after transplantation, the ability to produce normal antibody function recovers except in those patients experiencing chronic GVHD.

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