Chinese Journal of Tissue Engineering Research ›› 2020, Vol. 24 ›› Issue (31): 4986-4993.doi: 10.3969/j.issn.2095-4344.2141
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Pretreatment of unrelated umbilical cord blood transplantation without antithymocyte globulin for the treatment of acute myeloid leukemia and acute lymphoblastic leukemia: follow-up evaluation of 306 cases
Zhang Xuhan1, Wang Li2, Tang Baolin1, Wan Xiang1, Yao Wen1, Song Kaidi1, Sun Zimin1
- 1Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China; 2Department of Rehabilitation Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, Anhui Province, China
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Received:2020-02-29Revised:2020-03-06Accepted:2020-04-03Online:2020-11-08Published:2020-09-03 -
Contact:Sun Zimin, Chief physician, Professor, Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China -
About author:Zhang Xuhan, Master, Attending physician, Department of Hematology, The First Affiliated Hospital of USCT, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China -
Supported by:the National Natural Science Foundation of Chin, No. 81470350
CLC Number:
Cite this article
Zhang Xuhan, Wang Li, Tang Baolin, Wan Xiang, Yao Wen, Song Kaidi, Sun Zimin. Pretreatment of unrelated umbilical cord blood transplantation without antithymocyte globulin for the treatment of acute myeloid leukemia and acute lymphoblastic leukemia: follow-up evaluation of 306 cases[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(31): 4986-4993.
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Patient and transplant characteristics Patients and transplant characteristics are summarized in Table 1. Among 306 patients, 112 (36.6%) received transplantation for AML and 194 (63.1%) for ALL. Median age at UCBT was 13.87 years (range, 1-64 years) for patients with AML and 11.89 years (range, 1-50 years) for those with ALL. In the AML group, 65 patients (58%) were transplanted in CR1, 57 (18.7%) in CR2, and 25 (22.3%) in advanced disease status. For the ALL group, 103 patients (53%) were transplanted in CR1, 57 (29.4%) in CR2, and 24 (12.4%) in advanced disease status. Overall, 248 patients (81%) had high-risk disease at diagnosis. Among all patients, 31 (10.1%) received UCB that was 6/6 HLA matched, 152 (49.7%) with a 5/6 HLA match, and 123 (40.2%) with a 4/6 HLA match. A total 118 patients (38.5%) had matched donor ABO compatibility, 101 (33%) had major ABO mismatch, and 87 (28.4%) had minor ABO mismatch. There were 203 patients (66.3% of the entire population, of which 69 had AML and 134 had ALL) who received a conditioning regimen of BUCY2 in combination with fludarabine. Another 103 patients (33.3% of the total population, of which 43 had AML and 60 with ALL) received a conditioning regimen of total body irradiation cyclophosphamide plus cytarabine. For patients with AML, the median total nucleated cell dose and CD34+ cell dose was 4.25 × 107/kg (range: 1.71-17.27 × 107/kg) and 2.18 × 105/kg (range: 0.45-10.55 × 105/kg), respectively. For ALL patients, the median total nucleated cell dose and CD34+ cell dose was 4.22 × 107/kg (range: 1.69-13.5 × 107/kg) and 2.25 × 105/kg (range, 0.4-8.53 × 105/kg), respectively. "
Outcomes of transplantation For the total population of patients with AML and ALL, the engraftment of neutrophil and platelet were similar. The 30-day cumulative incidences of neutrophil engraftment after UCBT in the AML and ALL groups were 95.5% (95% CI: 89.1-98.2) and 94.8% (95% CI: 90.5-97.2), respectively (P=0.718). The median time to neutrophil recovery was 17 (range, 12-30) days and 16 (range, 10-31) days, respectively (Table 2). Fourteen patients did not engraft after UCBT (AML: 5 and ALL: 9); four of those patients—all of whom had ALL-died from severe infection and cerebral hemorrhage (two patients each). The 120-day cumulative incidences of platelet engraftment for AML and ALL was 83.9% (95% CI: 75.6-89.7) and 82.5% (95%CI: 76.3-87.2; P=0.733) and the median time to platelet recovery was 36 (range, 17-121) and 36 (range, 11-196) days, respectively. "
With respect to age groups (≤ 14 years, 15-39 years, ≥ 40 years) (Table 3), adolescents and young adults group had higher engraftment rates for AML than ALL. The 30-day cumulative incidence of neutrophil recovery was higher in patients with AML than in those with ALL (97.9%, 95% CI: 76.8-99.8, vs. 91.1%, 95% CI: 78.7-96.4, P=0.02). In multivariate analysis, CD34+ cell dose and conditioning regimen were independent factors influencing neutrophil recovery. The cumulative incidence of platelet recovery on day 120 was also higher in AML than in ALL (87.2%, 95% CI: 72.8-94.3, vs. 73.2%, 95% CI: 59.2-83.1; P=0.03). In multivariate analysis, CD34+ cell dose was the only independent factor influencing platelet recovery (Table 4). There was no difference between AML and ALL in the groups of children and old adults. "
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Incidences of acute and chronic GVHD For the total population of patients with AML and ALL, the cumulative incidences of acute GVHD (grade II-IV and grade III-IV) at 100 days were similar (grades II-IV: AML, 17.1% (95% CI: 10.8-24.7) and ALL, 14.5% (95% CI: 10.8-24.7), P=0.613; grades III-IV: AML, 11% (95% CI: 5.9-17.4) and children, 8% (95% CI: 4.9-12.7), P=0.489). The 2-years cumulative incidences of cGVHD in patients with AML and ALL were also similar (23%, (95% CI: 15.5-31.4) and 17%, (95% CI: 12.1-22.6, P=0.377). With grouping by age, cumulative incidences of aGVHD and cGVHD were still similar between AML and ALL in children, adolescents and young adults, and older adults. Relapse and non-relapse mortality, overall survival, and GRFS Fifty-four patients had relapse after UCBT (11 with AML and 43 with ALL). The cumulative incidence for relapse at 2 years in patients with ALL was higher than with AML (24%, 95% CI: 17.9-30.6, vs. 10.1% 95% CI: 5.1-17.1, P=0.01) (Figure 1). The median time to relapse was 12.7 (range, 1.1-59.6) months among AML and 10 (range, 1.5-34.8) months among ALL. In the analysis of age-group, both cumulative incidence of relapse and median time to relapse were significantly different between AML and ALL in adolescents and young adults group (relapse: 25%, 95% CI: 1.4-37.1, vs. 9%, 95% CI: 5.3-15.8, P=0.02); median time: 20.4 (range, 18.6-59.6) months vs. 8.1 (range, 2.8-17.7) months). There were no differences between AML and ALL in both children group and old adult group. In multivariate analysis, cGVHD was an independent factor influencing relapse. Sixty patients died without relapse, 23 with AML and 37 with ALL. The median time to non-relapse mortality in AML and ALL was 301 (range: 45-1 044) days and 121 (range: 3-1 392) days, respectively. The cumulative incidence of non-relapse mortality at 2 years was 21.4%(95% CI: 14.1-29.7) for AML and 18.1%(95% CI: 13.0-23.9) for ALL (P=0.738). Causes of death included pulmonary infection (n=30), hemorrhage (n=4), multiorgan failure (n=22), and other causes (n=4). There was no significant difference in non-relapse mortality between AML and ALL by age groups. The median follow-up duration was 21.6 (range, 3-80.7) months. Overall survival at 2 years in AML was similar to that in ALL (72%, 95% CI: 62-79.4, vs. 66%, 95% CI: 59.5-70.3, P=0.263). There was also no difference in overall survival between AML and ALL by age groups. The GRFS at 2 years in AML and ALL was 63.1% (95% CI: 52.9-71.7) and 56.2% (95% CI: 48.7-63.0), respectively (P=0.192). GRFS also showed no difference between AML and ALL by age groups. "
Immune reconstitution Considering the effect of age on the development of the immune system, the immune reconstitution was compared among age groups. In the comparison of outcomes between AML and ALL, we analyzed age groups ≤ 14 years and 15-39 years with respect to CD4+ T cells, CD8+ T cells, natural killer cells, and Treg cells at 1, 2, 3, 4,6, 12, and 18 months after CBT (Figure 2). The results showed that CD4+, CD8+, and Treg cells recovered with time after CBT whereas natural killer cells recovered more quickly (within 1 month) in patients in both age groups. In the group ≤ 14 years, CD4+ T cell counts in AML were lower than in ALL at 2 months after CBT whereas Treg cell counts in AML were higher than in ALL at 4 months post CBT. There was no difference seen in CD8+ and natural killer cells between AML and ALL. The proportion of CD4/CD8 T cells was lowest at 2 months and recovered at 4 months after CBT. In the age group 15-39 years, CD8+ T cell counts in AML at 4 months post CBT were higher than in ALL whereas CD4+, Treg, and natural killer cells showed no difference between AML and ALL. The proportion of CD4+/CD8+ T cells was lowest at 3 months and recovered at 12 months post CBT. "
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