Graft-Versus-Host Disease After Bone Marrow Transplantation for Thalassemia

We evaluated the incidence of GVHD, risk factors and the impact of graft composition on acute GVHD (aGVHD) in 92 children who underwent BMT for thalassemia following busulfan/cyclophosphamide (BUCY)-based conditioning regimens and GVHD prophylaxis with CSA/short-MTX and methylprednisolone. The incidence of grade 2-4 and 3-4 aGVHD was 35% (95% confidence interval (CI) 25-44) and 9% (95% CI 4-16), respectively. We found that CD3 þ and CD34 þ cell doses above the median were associated with high incidence of grade 2-4 aGVHD (49 vs 20%, P ¼ 0.005 and 46 vs 23%, P ¼ 0.021, respectively). In multivariate analysis, high CD3 þ (hazard ratio (HR) 4.6; 95% CI 1.4-14.7; P ¼ 0.010) and CD34 þ (HR 4.3; 95% CI 1.4-12.7; P ¼ 0.011) cell doses were associated with grade 2-4 aGVHD. We further examined the effect of CD3 þ and CD34 þ cell doses on aGVHD using quartile cutoff points and found a minimum threshold for CD3 þ (38 Â 10 6 /kg) and CD34 þ (4 Â 10 6 /kg) cells above which the incidence of grade 2-4 aGVHD is significantly increased. This study shows for the first time a positive correlation between the number of CD3 þ and CD34 þ cells and aGVHD in children receiving sibling BMT, and indicates that using tailored and more intensive post transplant immunosuppression may permit to better control aGVHD.

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Higher CD3+ and CD34+ cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia

Gaziev

Isgrò

Marziali

et al. 2011

“…Other studies have also addressed the impact of risk factors on post-BMT complications. [6][7][8][9][10] During the past decades we have improved our ability to prevent and/or treat such complications, and transplantrelated mortality (TRM) has been considerably reduced 11 and delayed: in our HLA-identical sibling program TRM was 39% before 1990 (385 patients) and occurred at a median interval of 48 days from BMT (range 1-1230); TRM is currently 17% (333 patients) with a median interval from transplant of 103 days (range 8-1419) (P Ͻ 0.00001) (unpublished). Very few patients die before day +7: the 10th percentile is currently day 30, and the 75th percentile is day 202.…”

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confidence: 99%

Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin

Bacigalupo

Oneto

Bruno

et al. 1999

Summary:Transplant-related mortality (TRM) following allogeneic bone marrow transplantation (BMT) remains a major concern and early identification of patients at risk may be clinically relevant. In this study we describe a predictive score based on bilirubin and blood urea nitrogen (BUN) levels on day +7 after BMT. The patient population consisted of 309 consecutive patients who underwent BMT from sibling (n = 263) or unrelated donors (n = 46) for hematologic disorders between December 1990 and December 1996. Of 27 laboratory tests taken on day +7 after BMT, serum bilirubin (P = 0.02) and BUN (P = 0.007) were found to be independent predictors of TRM in multivariate analysis. The median levels of bilirubin (0.9 mg/dl) and of BUN (21 mg/dl) were then used as a cut-off and a score of 1 was given for values equal/greater than the median. There were 216 patients with scores 0-1 (low risk) on day +7 (bilirubin Ͻ0.9 and/or BUN Ͻ21) and 93 patients with score 2 (high risk) (bilirubin у0.9 and BUN у21): the latter had more grade III-IV acute graft-versus-host disease (P = 0.03), slower neutrophil (P = 0.02) and slower platelet engraftment (P = 0.002). The actuarial 5 year TRM is 22% for low risk vs 44% for high risk patients (P = 0.0003). For HLA-identical siblings TRM is 20% vs 35% (P = 0.01), for unrelated donors it is 20% vs 65% (P = 0.01). Day +7 score was highly predictive of TRM on multivariate analysis (hazard ratio 1.9, P Ͻ 0.01), after adjustment for year of transplant (P Ͻ 0.00001), unrelated vs sibling donors (P = 0.001), patient age (P = 0.01) and diagnosis (P = 0.01). These results were validated on an independent group of 82 allogeneic BMT recipients in a pediatric Unit who showed an actuarial TRM of 16% for low risk vs 46% for high risk patients (P = 0.002). This study suggests that it may be possible to identify patients with different risks of TRM on day +7 after BMT: high risk patients could be Allogeneic bone marrow transplantation (BMT) is associated with considerable morbidity and mortality, and several studies have addressed the issue of risk factors for major single complications such as interstitial pneumonitis, 1 acute GVHD 2,3 and graft rejection: 4 patient variables (older age), donor variables (older age, parous female donors for male recipients, degree of HLA matching) and transplant variables (longer interval from diagnosis to transplant, intensive regimens), are among these. A study from the Seattle group has looked at risk factors for veno-occlusive disease of the liver, another important complication of allogeneic BMT 5 and found that early increments in serum bilirubin level and body weight were highly predictive. Other studies have also addressed the impact of risk factors on post-BMT complications. [6][7][8][9][10] During the past decades we have improved our ability to prevent and/or treat such complications, and transplantrelated mortality (TRM) has been considerably reduced 11 and delayed: in our HLA-identical sibling program TRM was 39% before 1990 (385 patients) and occurred at a...

“…It has been shown that cyclosporine plus methotrexate are superior to cyclosporine or methotrexate alone, and cyclosporine plus methotrexate plus steroids are superior to cyclosporine plus methotrexate. 4,87,88 Long-term cyclosporine extended up to 12 months after BMT may decrease the incidence of cGVHD. 4,89 In vivo ablation of alloreactive donor T cells after allogeneic hematopoietic transplantation could significantly contribute to preventing and treating GVHD.…”

Section: Prevention Of Chronic Graft-versus-host Diseasementioning

confidence: 99%

“…4,9 It has been suggested that four features of cGVHD at presentation predict poor outcome: progressive presentation of disease, concomitant thrombocytopenia, lichenoid skin or mucose-membrane histology and liver dysfunction. 10,11 Despite the improved survival in patients with established cGVHD due to the conventional, new approved and investigational therapies, many patients continue to have poor clinical function.…”

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confidence: 99%

Chronic graft-versus-host disease: is there an alternative to the conventional treatment?

Gaziev¹,

Galimberti²,

Lucarelli³

et al. 2000