scholarly journals Umbilical Cord Blood Microtransplantation in Newly Diagnosed, Elderly Patients with Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2878-2878
Author(s):  
Wen Yao ◽  
Liangquan Geng ◽  
Dongyao Wang ◽  
Huilan Liu ◽  
Baolin Tang ◽  
...  

Abstract Objective: We observed the efficacy and safety of umbilical cord blood microtransplantation (UCBMT) in the treatment of newly diagnosed with acute myeloid leukemia (AML) in the elderly. Methods: Prospective one-arm phase I clinical study. The patients should meet the following criteria: 60-80-year-old; newly diagnosed AML; receive the treatment of chemotherapy combined with UCBMT. Result: In total, 11 patients newly diagnosed with AML received chemotherapy in combination with UCBMT, from November, 2019 to January, 2021, including 7 males and 4 females. The average age was 71 (60-80). For the patients, 7 cases with normal chromosome karyotype, and 2 cases with +8 chromosome, 1 case with 7q- chromosome, and 1 case with karyotype of monomer. In the 7 patients with normal chromosome karyotype, 3 cases were FMS-liketyrosine kinease 3 (FLT3) positive (2 of them in combination with nucleophosmin 1 (NPM1) mutation); in addition, in 4 patients of the 7, one showed double mutation of CEBPA, one showed NPM1 mutation, one showed IDH1 mutation, and one showed IDH2 mutation. In 4 patients with chromosomal abnormalities, one patient showed no special gene, one patient showed ASXL1 mutation, one patient was IDH1 mutation, and one patient was TP53 mutation. All of the patients were treated with IA (IDA 8-10 mg/ m 2/day x 3 days, cytarabine 100 mg/ m 2/day x 7 days) for inducing chemotherapy. For the patients with 60-70-year-old, they were treated with IDA (8 mg/ m 2/day); and for the patients with 70-80-year-old, they were treated with darubicin (10 mg/ m 2/day). In the consolidation phase, the patients were treated with cytarabine (1 g/ m 2, q12h) for 3 consecutive days. There were 3 courses of consolidation chemotherapy. Next, patients received single unrelated cord blood transplantation (UCBT) from China's public umbilical cord blood bank, HLA matching was performed for all patients before treatment. A total of 4 units of UCB with HLA 0-3/6(HLA-A,-B,-DR)matching and the ABO blood type matched with the patient were transfused after induction and consolidation chemotherapy for 24-48 hours, then with follow-up. At the same time, the immunological characteristics of these patients were fully analyzed. We demonstrated that, 8 of 11 patients received one course of induction chemotherapy, and achieved a complete response. The complete response rate was 72.7%. What's more, the median time for neutrophils ≥ 0.5 x 10 9/L and platelete ≥ 20 x 10 9/L was 12 days. There were no treatment-related deaths during induction therapy. The median follow-up was 14 (7-31) months. 1 patient showed monomer karyotype with P53 gene mutation, and got complete remission after one course of induction chemotherapy with IA. However, the patient died for AML recurred. For the other 10 patients, they were alive, and the OS of 1 year was 89.8%. Moreover, we found the expression of PD-1 on CD8 +T cells decreased, while the expression of CD38 increased after therapy. Besides, the proportion of NKp30 +NK cells, as well as the IFN-γ +TFN-α +NK cells increased significantly. Conclusion: UCBMT therapy for newly diagnosed elderly AML patients could accelerate the recovery of hematopoietic function and improve the safety of chemotherapy. This method is effective and worthy of further promotion. Disclosures No relevant conflicts of interest to declare.

2014 ◽  
Vol 34 (2) ◽  
pp. 92-97 ◽  
Author(s):  
Vic J.F. Van Loon ◽  
Carmen J.W. Scheffer ◽  
Herman J. Genn ◽  
Arie C. Hoogendoorn ◽  
Jan W. Greve

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5162-5162
Author(s):  
Ying Pang ◽  
Ying Feng ◽  
Xue Ye ◽  
Hanyun Ren

Abstract Objective To explore the feasibility, long-term hematopoiesis and complication of transplantation with two units of HLA-mismatched unrelated umbilical cord blood in treatment of adult acute myeloid leukemia. Methods A 32 years old, 50kg male with acute myeloid leukemia in complete remission received transplantation with two units of HLA-mismatched unrelated umbilical cord blood.The conditioning regimen were modified(BU/CY)+ATG. The prophylaxis regimen for graft versus-host disease(GVHD) consisted of cyclosporine(CSA) and mycophenolate mofetil(MMF). The umbilical cord blood obtained from two different donors, both with mismatched HLA B/DRB locus from the recipient and mismatched HLA- B locus between the two donors. The umbilical cord blood was preserved in liquid nitrogen, recovered in a 40o C water bath immediately, infused via a catheter from the femoral artery to the arc of aorta, The doses of nucleated cells infusion were 4.4×107/kg (from donor 1) and 2.8×107/kg (from donor 2). Results An absolute neutrophil count of more than 0.5×109/L at day 26,and a platelet count of more than 20×109/L at day 42. Septicemia with MRSA and pseudomomanas occurred at day 9 and day 14 because of agranulocytosis. The infection was controlled by Vancomycin, Tienam and HD-dose Gama immunoglobulin. Neither acute nor chronic GVHD developed in a follow-up period of 90 days. DNA-STR and HLA distinct analysis assay revealed a complete implant of cells from only one donor(donor2). Conclusions 1.No donor with matched HLA bone marrow stem cell was available for the adult patient at the time of his relapse. HLA mismatched umbilical cord blood was obtained from two donors. Although cell counts for transplantation are much lower than the requirement of routine bone marrow transplantation, the speed of blood cell regeneration in the recipient is compatible with routine bone marrow transplantation. 2.Furthermore, Although DNA-STR and HLA analysis indicate complete implant of cells from only one donor, the result indicates transplantation with umbilical cord blood cells obtained from two different donors is promising in the situation where the cell number obtained from one donor is not enough.3.HLA- B/DRB locus was mismatched in the two donors. GVHD did not develop even after tapered off immunosuppresents 3 months post transplantation. No cross rejection observed by clinical presentation and blood cell analysis. The results indicate the incidence of GVHD is low after umbilical cord blood transplantation.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4422-4422
Author(s):  
Chi Kong Li ◽  
Vincent Lee ◽  
Frankie WT Cheng ◽  
Karen Li ◽  
Kent KS Tsang ◽  
...  

Abstract Unrelated umbilical cord blood transplant (UCBT) was performed in 24 children (16 M, 8 F) with leukemia in a single institution from June 1998 to May 2008. The leukemia types were Acute Lymphoblastic Leukemia (ALL, n=13), Acute Myeloid Leukemia (AML, n=9) and Juvenile Myelomonocytic Leukemia (JMML, n=2). The disease status was CR2 in 13, CR3/4 in 3, refractory or relapse in 8. Fifteen patients received single unit (SU) and 9 patients received double unit (DU) UCBT. The mean age and body weight were 5.7 ± 3.7 year and 19.5 ± 7.9 kg for SU, 7.7 ± 4.0 year and 24.6 ± 9.9 kg for DU, respectively. The sources of cord blood units were from local public CB bank (n=20) and 4 overseas public CB banks (n=4). The cord blood units were not more than 2 HLA antigen mismatches from the patients, and the DU cord blood were also not more than 2 antigen mismatches between each other. The minimal requirement was nucleated cell (NC) dose > 2.5×107/kg for SU, and > 3.7 ×107/kg for DU. The conditioning was TBI based for ALL and busulphan-based for myeloid leukemia. ATG was routinely included except in 5 patients. The engraftment rate was 70.8% for the whole group, and 66.7% and 77.8% for SU and DU, respectively. All the 4 overseas UCBT failed to engraft and the engraftment rate for local CB bank units was 85%. The 2 JMML had failed engraftment, one received SU and 1 DU. There was no significant difference in the transplanted cell dose for SU and DU (combined dose), NC 6.2±3.8×107/kg vs 8.2±3.5×107/kg, CD34 cell 5.0±7.2 ×105/kg vs 3.8±1.3×105/kg, respectively. However patients who had successful engraftment received higher cell dose, NC 7.9±3.9×107/kg vs 4.5±1.8×107/kg (p=0.042), CD34 cell 5.4±6.3 ×105/kg vs 2.2±1.6×105/kg (p=0.073), respectively. All the 9 DU UCBT showed signs of engraftment with donor DNA detected, but two did not achieve neutrophil engraftment and subsequently failed engraftment. On the first chimerism study on Day 7–10, 3 had mixed chimerism (MC, 50–60% vs 40–50%) and 2 became single donor complete chimerism (CC) in the second week study, one had persistent MC up to 1 month but required second transplant for failed neutrophil engraftment. Six patients had CC with single CB unit since the week 1 and were maintained in 5, and another one had failed neutrophil engraftment. Finally 7 DU UCBT had sustained CC with single donor unit, however the finally successfully engrafted unit had lower CD34 cell dose as compared to the non-engrafted unit (1.5±0.5×105/kg vs 2.4±1.1 ×105/kg, p=0.004), and the NC dose of the 2 units in DU was similar (3.6±1.7.×107/kg vs 4.4±1.8×107/kg (p=0.042). There was no difference in the degree of HLA mismatch between the engrafted and non-engrafted units of DU. The neutrophil engraftment was more rapid with SU as compared with DU, 14.5 vs 19.7 days, p=0.021, the platelet engratment and number of red cell and platelet transfusion was not different. All those with engraftment developed acute GVHD, and the incidence of grade III–IV was similar between SU and DU (33.3% vs 28.6%), and none died from AGVHD. Nine patients died of non-engraftment or transplant related mortality, 3 from leukemia relapse and 12 were alive (7 patients > 3 years). The 2-year survival after UCBT was 47%. In conclusion, DU cord blood could achieve a higher NC dose, but the engraftment of DU was always single unit and 33% had transient MC in the very early week of UCBT. The DU approach may enhance the engraftment of the finally engrafted unit even that had a lower CD34 cell dose.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4399-4399 ◽  
Author(s):  
Carmen Martinez ◽  
Jorge Gayoso ◽  
Carmen Canals ◽  
Herve Finel ◽  
Andrea Bacigalupo ◽  
...  

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is currently considered the standard of care for those patients with HL that relapse after autologous HSCT. Several studies have shown that fit patients with chemosensitive disease can benefit from alloHSCT using and identical sibling (SIB) or matched-unrelated (MUD) donors. Recently, encouraging results have been obtained using haploidentical donors (HAPLO) and post-transplantation cyclophosphamide (ptCY) as graft-versus-host disease prophylaxis (GVHD). Because information regarding the results of alloHSCT using alternative donors is still scarce, we aimed to compare outcome of umbilical cord blood (UCB) and HAPLO transplants with conventional SIB and MUD for HL. Patients and methods: Information of patients older than 17y with HL who received an alloHSCT from a SIB, MUD (8/8 antigen matched), UCB or a ptCY-based HAPLO between 2010-2013 was downloaded from the EBMT and GETH databases. Results: 773 patients with HL were identified meeting the inclusion criteria. 339 received a transplant from a SIB donor, 276 from a MUD, 101 from HAPLO, and 47 from UCB. A significant higher number of patients treated with alloHSCT from UCB and HAPLO donors received reduced intensity (RIC) regimens in comparison to SIB and MUD (76% and 88% vs. 69% and 69%, respectively, p=0.001). Bone marrow was more frequently used as source of stem cells in the HAPLO group in relation to SIB and MUD (61% vs 10% and 11%, respectively, p=0.001), Other variables such as sex, age, performance status, chemorefractory disease, and previous autologous SCT were balanced. Median follow-up after alloHSCT for all patients was 12 months (1-60). The 1-year probabilities of overall survival (OS) and progression-free survival (PFS) were 80% and 49% after SIB transplant, 69% and 54% after MUD, 65% and 40% after UCB, and 73% and 56% after HAPLO, respectively. The 1-year probabilities of non-relapse mortality (NRM) and relapse rate (RR) were 12% and 38% after SIB, 21% and 25% after MUD, 20% and 40% after UCB, and 18% and 27% after HAPLO. Multivariate analysis showed that, in comparison with standard SIB alloHSCT, UCB was associated with a trend to a higher NRM (p=0.08) and RR (p=0.06), leading to a significant lower OS and PFS (p=0.009, HR 2.1, 95% CI 1.2-3.6; p=0.02, HR 1.6, 95% CI 1.1-2.3; respectively). NRM was also significantly higher after MUD (p=0.004, HR 1.8, 95% CI 1.2-2.6), but in contrast, RR was lower (p=0.003 HR 0.6, 95%CI 0.5-0.9) with a lower OS (p=0.002, HR 1.6, 95% CI 1.2-2.1) and no significant differences in PFS. No significant differences were observed between HAPLO and SIB in NRM, RR, PFS and OS. Conclusions: This registry study suggests that in adults with advanced HL, the outcome of pt-CY-based HAPLO HSCT may be comparable to that of conventional SIB alloHSCT and MUD across multiple centers and conditioning regimens. These findings need to be corroborated by longer follow-up. Figure 1. Figure 1. Disclosures Peggs: Autolus: Consultancy, Equity Ownership; Cellectis: Research Funding. Milpied:Celgene: Honoraria, Research Funding. Afanasiev:CELLTRION, Inc.: Research Funding. Russell:Therakos: Other: shares. Sureda:Takeda: Consultancy, Honoraria, Speakers Bureau.


Sign in / Sign up

Export Citation Format

Share Document