scholarly journals Evaluation of a CD5-specific immunotoxin for treatment of acute graft- versus-host disease after allogeneic marrow transplantation

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 824-830 ◽  
Author(s):  
PJ Martin ◽  
BJ Nelson ◽  
FR Appelbaum ◽  
C Anasetti ◽  
HJ Deeg ◽  
...  
Keyword(s):  
Placebo Group ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Complete Response ◽  
Control Group ◽  
Graft Versus Host ◽  
Allogeneic Marrow Transplantation ◽  
Allogeneic Marrow ◽  
Acute Graft

Acute graft-versus-host disease (GVHD) is most often treated with high dose glucocorticoids, but less than half of patients have durable overall improvement. Previous phase I and phase II studies suggested that treatment with a CD5-specific immunotoxin (XomaZyme-CD5 Plus) could ameliorate symptoms of GVHD. In a randomized, double-blind trial, we compared XomaZyme-CD5 Plus and glucocorticoids versus placebo and glucocorticoids as initial therapy for 243 patients who developed acute GVHD after allogeneic marrow transplantation. The study drug (XomaZyme. CD5-Plus or an identical appearing placebo) was administered at a dose of 0.1 mg/kg body weight on each of 14 consecutive days. All patients were treated concomitantly with a standard regimen of methylprednisolone. At the time of entry on study, 94% of patients had a rash, 56% had hyperbilirubinemia, 61% had diarrhea, and 84% had nausea and vomiting. At 3, 4, and 5 weeks after starting treatment, symptom severity was less in the CD5 group than in the placebo group. At 4 weeks, 40% of patients assigned to the CD5 group had complete response compared with 25% of those assigned to the control group (P = .019). At 6 weeks, 44% of patients assigned to the CD5 group had complete response as compared with 38% in the placebo group (P = .36). Clinical extensive chronic GVHD developed in 65% of patients in the CD5 group compared with 72% in the control group (P = .35). Survival at 1 year after treatment was 49% in the CD5 group and 45% in the control group (P = .68). Side effects required close monitoring and appropriate adjustment of treatment. The combined administration of a CD5-specific immunotoxin and glucocorticoids controls GVHD manifestations more effectively than treatment with glucocorticoids alone during the first 5 weeks after starting treatment. Use of this immunotoxin does not result in any long-term clinical benefit for patients with acute GVHD.

scholarly journals Evaluation of a CD5-specific immunotoxin for treatment of acute graft- versus-host disease after allogeneic marrow transplantation

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 824-830 ◽  
Author(s):  
PJ Martin ◽  
BJ Nelson ◽  
FR Appelbaum ◽  
C Anasetti ◽  
HJ Deeg ◽  
...  
Keyword(s):  
Placebo Group ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Complete Response ◽  
Control Group ◽  
Graft Versus Host ◽  
Allogeneic Marrow Transplantation ◽  
Allogeneic Marrow ◽  
Acute Graft

Abstract Acute graft-versus-host disease (GVHD) is most often treated with high dose glucocorticoids, but less than half of patients have durable overall improvement. Previous phase I and phase II studies suggested that treatment with a CD5-specific immunotoxin (XomaZyme-CD5 Plus) could ameliorate symptoms of GVHD. In a randomized, double-blind trial, we compared XomaZyme-CD5 Plus and glucocorticoids versus placebo and glucocorticoids as initial therapy for 243 patients who developed acute GVHD after allogeneic marrow transplantation. The study drug (XomaZyme. CD5-Plus or an identical appearing placebo) was administered at a dose of 0.1 mg/kg body weight on each of 14 consecutive days. All patients were treated concomitantly with a standard regimen of methylprednisolone. At the time of entry on study, 94% of patients had a rash, 56% had hyperbilirubinemia, 61% had diarrhea, and 84% had nausea and vomiting. At 3, 4, and 5 weeks after starting treatment, symptom severity was less in the CD5 group than in the placebo group. At 4 weeks, 40% of patients assigned to the CD5 group had complete response compared with 25% of those assigned to the control group (P = .019). At 6 weeks, 44% of patients assigned to the CD5 group had complete response as compared with 38% in the placebo group (P = .36). Clinical extensive chronic GVHD developed in 65% of patients in the CD5 group compared with 72% in the control group (P = .35). Survival at 1 year after treatment was 49% in the CD5 group and 45% in the control group (P = .68). Side effects required close monitoring and appropriate adjustment of treatment. The combined administration of a CD5-specific immunotoxin and glucocorticoids controls GVHD manifestations more effectively than treatment with glucocorticoids alone during the first 5 weeks after starting treatment. Use of this immunotoxin does not result in any long-term clinical benefit for patients with acute GVHD.

Serum Cyclosporine Concentration and Risk of Acute Graft-versus-Host Disease after Allogeneic Marrow Transplantation

1988 ◽  
Vol 319 (2) ◽  
pp. 65-70 ◽  
Author(s):  
Gary C. Yee ◽  
Steven G. Self ◽  
Timothy R. McGuire ◽  
Julie Carlin ◽  
Jean E. Sanders ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Host Disease ◽  
Graft Versus Host ◽  
Allogeneic Marrow Transplantation ◽  
Allogeneic Marrow ◽  
Acute Graft

Correlation Between Disparity for the Minor Histocompatibility Antigen HA-1 and the Development of Acute Graft-Versus-Host Disease After Allogeneic Marrow Transplantation

Blood ◽  
1999 ◽  
Vol 94 (8) ◽  
pp. 2911-2914 ◽  
Author(s):  
Li-Hui Tseng ◽  
Ming-Tseh Lin ◽  
John A. Hansen ◽  
Ted Gooley ◽  
Ji Pei ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Odds Ratio ◽  
Acute Gvhd ◽  
Histocompatibility Antigen ◽  
Minor Histocompatibility Antigen ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Allogeneic Marrow Transplantation ◽  
Allogeneic Marrow ◽  
Acute Graft

Results of a previous study suggested that recipient mismatching for the minor histocompatibility antigen HA-1 is associated with acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. In that study, most patients received either cyclosporine or methotrexate for GVHD prophylaxis, and a cytotoxic T-cell clone was used to test for HA-1 disparity. To facilitate large-scale testing, we developed a method that uses genomic DNA to identify HA-1 alleles. A retrospective study was conducted to correlate HA-1 disparity and the occurrence of acute GVHD in 237 HLA-A2–positive white patients who had received a marrow or peripheral blood stem cell transplant from an HLA-identical sibling. All patients received both methotrexate and cyclosporine for GVHD prophylaxis. The presence of HLA-A*0201 was confirmed in 34 of the 36 HA-1 disparate pairs by sequencing the HLA-A locus. Grades II-IV GVHD occurred in 22 (64.7%) of these 34 patients, compared with 86 (42.8%) of the 201 patients without HA-1 disparity (odds ratio, 2.45; 95% confidence interval [CI], 1.15 to 5.23; P = .02). Recipient HA-1 disparity showed a trend for association with acute GVHD (odds ratio, 2.1; 95% CI, 0.91 to 4.68; P = .08) when a multivariable logistic regression model was used to include additional risk factors. These data are consistent with results of the previous study, suggesting an association between HA-1 disparity and risk of acute GVHD, but the strength of this association may be lower in patients who received both methotrexate and cyclosporine than in those who received methotrexate or cyclosporine alone.

A CHRONIC PULMONARY SYNDROME ASSOCIATED WITH GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC MARROW TRANSPLANTATION

1992 ◽  
Vol 54 (6) ◽  
pp. 1002-1007 ◽  
Author(s):  
ANTHONY P. SCHWARER ◽  
J. MICHAEL B. HUGHES ◽  
BEATRICE TROTMAN-DICKENSON ◽  
THOMAS KRAUSZ ◽  
JOHN M. GOLDMAN
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Host Disease ◽  
Graft Versus Host ◽  
Allogeneic Marrow Transplantation ◽  
Allogeneic Marrow

scholarly journals Evidence that sustained growth suppression of intestinal anaerobic bacteria reduces the risk of acute graft-versus-host disease after sibling marrow transplantation

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2668-2676 ◽  
Author(s):  
DW Beelen ◽  
E Haralambie ◽  
H Brandt ◽  
G Linzenmeier ◽  
KD Muller ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Anaerobic Bacteria ◽  
Underlying Disease ◽  
Growth Suppression ◽  
Graft Versus Host ◽  
Sustained Growth ◽  
Acute Graft

Abstract The influence of intestinal bacterial decontamination on the occurrence of grades II to IV acute graft-versus-host disease (GVHD) was retrospectively analyzed in 194 predominantly adult patients treated by genotypically identical sibling marrow transplantation under conditions of strict protective isolation and intestinal antimicrobial decontamination. Forty-five patients (23%) developed acute GVHD and univariate analysis identified four features that significantly increased the risk for this reaction: chronic myeloid leukemia as the underlying disease, as compared with all other disease categories (P < .0001); female marrow donors for male recipients, as compared with other gender combinations (P < .005); ineffective, as compared with sustained growth suppression of intestinal anaerobic bacteria (P < .006); and methotrexate as the sole immunoprophylactic compound, as compared with cyclosporine containing regimens (P < .05). Using the duration of anaerobic growth suppression as a time-dependent explanatory variable, proportional hazards regression analysis confirmed these features as independent predictors for acute GVHD with relative risk estimates of 1.9 (95% confidence interval [CI], 1.3 to 2.7) for the immunoprophylactic regimen (P < .0004), of 1.8 (95% CI, 1.3 to 2.5) for the underlying disease (P < .0005), of 1.7 (95% CI, 1.2 to 2.5) for anaerobic decontamination (P < .002), and of 1.3 (95% CI, 1.1 to 1.6) for the donor/recipient gender combination (P < .008), respectively. Best subset selection modeling also identified the quality of anaerobic decontamination as the third most important predictor for acute GVHD, when all four significant features were included. Estimates of acute GVHD stratified by the quality of anaerobic bacterial growth suppression showed a strong influence of anaerobic decontamination in patients burdened by at least one of the other unfavorable factors (P < .009). In conclusion, this study provides strong evidence that sustained growth suppression of intestinal anaerobic bacteria after clinical sibling marrow transplantation can independently modulate the occurrence of grades II to IV acute GVHD, which is in concordance with previous results from animal transplantation models. Antimicrobial chemotherapy specifically targeted to the intestinal anaerobic bacterial microflora may be complementarily useful in preventing acute GVHD and should be investigated in a prospective trial.

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