Chronic Graft Versus Host Disease (cGVHD) Following Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT): Higher Response Rate in Recipients of Unrelated Donor (URD) Umbilical Cord Blood (UCB).

Abstract

The nature of chronic graft versus host disease (cGVHD) after umbilical cord blood (UCB) transplant has not been well characterized. We analyzed clinical presentation and response to treatment in 170 patients with cGVHD (123 following transplant from an unrelated donor (URD) and 47 following transplant from UCB). URD transplant recipients were significantly younger (median age 25 (0.5–57) versus 39 (0.2–61) years, p = 0.002; and were less likely to receive a transplant from an HLA mismatched donor (33% versus 90%, p<0.0001). Seven% and 43% of patients underwent a transplant using a non myeloablative conditioning in the URD and UCB groups, respectively (p< 0.001). Progressive onset of cGVHD was seen in 27% and 19% of patients in URD and UCB cohorts (p =0.15) and platelet count of < 100,000/μl was seen in 36% and 15% of patients (p =0.014), respectively. The median follow up was 5 (0.14–10.8) and 1.5 (0.02–8.8) years in the 2 groups, respectively. A higher rate of response (CR+PR) to treatment was seen in UCB group across all time periods. Rates of response were 48% versus 74% at 2 months (p =0.005); 49% versus 78% at 6 months (p =0.001) and 51% versus 72% at 1 year (p =0.03) in the URD and UCB groups, respectively. Overall survival at 2 years was 59% (50–67%) versus 71% (53–83%) at 2 years and at 5 years was 54% (44–63%) versus 64% (42–79%) (p=0.17). In multivariate analysis, progressive onset of CGVHD (RR=2.3, 95% CI 1.4–3.8−2.3,p=0.002), platelet count of <100,000/μl (RR=3.5, 95% CI 1.7–7.3,p=0.0009), liver involvement (RR=2.5, 95% CI 1.4–4.6,p=0.002), and no CR or PR at 2 months (RR=3.5, 95% CI 2.1–5.9,p<0.0001) were associated with significantly increased mortality. These data suggests that among patients undergoing transplant from unrelated donor or cord blood, despite similar clinical presentation, higher rates of response to treatment were seen in UCB recipients. Early identification of high risk groups (progressive onset, less than PR at 2 months, platelet count < 100,000/μl and liver involvement should facilitate timely assignment of intensified therapy. Response to Treatment Response 2 mo 2 mo 6 mo 6 mo 1 year 1year URD UCB URD UCB URD UCB CR+PR 49 (48) 29 (74) 54 (49) 32 (78) 53 (51) 23 (72) SD+Prog 53 (52) 10 (26) 56 (51) 9 (22) 52 (49) 9 (28)

Similar outcomes of allogeneic hematopoietic cell transplantation from unrelated donor and umbilical cord blood vs. sibling donor for pediatric acute myeloid leukemia: Multicenter experience in China

“…So higher degrees of HLA mismatches between UCB and patients have been proved to be better tolerated by means of a reduced risk for lethal GVHD, lower incidences of cGVHD, and more treatment responsive GVHD. Hwang et al reported a meta-analysis of studies of UCB and URD in pediatric AML and found that the incidence of cGVHD was lower with UCBT, but the incidence of grade III-IV aGVHD did not differ (24)(25)(26).…”

Clinical outcomes of unrelated cord blood transplantation in children with malignant and non‐malignant diseases: Multicenter experience in China

“…Extensive research over recent years has established the safety and efficacy of UBCT in children with a variety of malignant and nonmalignant diseases. 6,15,16 UBCT presents the following advantages: a lower incidence and lower severity of GVHD, 17,18 in patients with leukemia 20,21 showed that the median duration to neutrophil and platelet engraftment was 23-27 and 38-60 days, respectively. Other studies 3,15,25 showed that UCBT was effective in children with non-malignant diseases, in whom the median duration to neutrophil and platelet recovery was 22-25 and 40-87 days, respectively.…”

“…In the malignant disease group, three patients who received UCB died before engraftment. The median duration to neutrophil and platelet engraftment was 16 [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] and 35 (6-107) days, respectively ( The median duration to neutrophil engraftment and platelet engraftment was similar between the two groups (P = .986, P = .133).…”

Extracorporeal photopheresis for graft‐versus‐host disease: the role of patient, transplant, and classification criteria and hematologic values on outcome—results from a large single‐center study

“…A total of 34 patients underwent ECP for steroid-refractory aGVHD from June 2001 to September 2013. A median of 11 ECP procedures per patient were performed (range, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. The median follow-up for surviving patients was 4 years (range, 2 months-12 years), while it was 7 months for deceased patients (range, 35 days-11 months).…”

“…7,8 Furthermore, despite better donor selection, GVHD prophylaxis, and treatment, chronic GVHD (cGVHD) affects 50% of long-term transplant survivors and is lethal in 20% to 40% of affected patients. 9 Primary therapy for extensive cGVHD usually includes steroids and calcineurin inhibitors, [10][11][12][13][14][15][16][17][18] but the probability of cGVHD response is highly variable. [19][20][21][22][23] Extracorporeal photopheresis (ECP) was introduced nearly 30 years ago to treat cutaneous T-cell lymphoma and autoimmune diseases, such as scleroderma.…”