High Rate of Engraftment and Low Regimen-Related Toxicity Using Fludarabine, Melphalan and Thiotepa Conditioning for Unrelated Donor Cord Blood Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4414-4414
Author(s):  
Stefan O Ciurea ◽  
Partow Kebriaei ◽  
Issa F Khouri ◽  
Muzaffar H. Qazilbash ◽  
Roy B Jones ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Adult Patients ◽  
High Rate ◽  
Unrelated Donor ◽  
Platelet Recovery ◽  
Blood Transplantation

Abstract BACKGROUND: Cord blood transplantation (CBT) represents an alternative source of stem cells for adult patients who lack a matched sibling or unrelated donor. However, the optimal type and intensity of the preparative regimen for patients receiving a CBT is not clear. We hypothesized that a conditioning regimen consisting of fludarabine, melphalan and thiotepa will be associated with an acceptable rate of engraftment and treatmentrelated mortality in patients receiving a CBT. METHODS: 37 patients, median age 31 years (2–57) and a median weight of 73kg, were treated between 8/2003 and 5/2008. All had advanced hematologic malignancies (24 with acute leukemia, 12 with lymphoma and one with CLL) At the time of transplant, 21 pts (57%) were in complete remission (CR) (first CR=20%) and 16 had relapsed/refractory disease. Grafts consisted of double (29 pts) or single (8 pts) CB units. Cytogenetics for patients with acute leukemia were poor in 11, intermediate in 9, good in 1 and unknown in 3 pts. Donor recipient HLA matching was (intermediate resolution class I HLA A and B and high-resolution DRB1): 3/6 (n=1, 1.5%), 4/6 (n=47, 71.2%) and 5/6 (n=18, 27.3%) alleles (n=66 units). Median total nucleated cell count was 1.8×107/kg (range 1–5.8). Nineteen patients received ex-vivo expanded units. The conditioning regimen consisted of melphalan 140 mg/m2 on day -8, thiotepa 10 mg/m2 on day -7, fludarabine 160 mg/m2 over 4 days on days -6, -5, -4, -3, and rabbit ATG 1.25 mg/kg on day -4 and 1.75 mg/kg on day -3 (FMT). Patients with CD 20+ lymphoid malignancies also received rituximab 375mg/m2 on day -9 (n=8, 22%). GVHD prophylaxis was tacrolimus and mini-methotrexate in 23 (62%) and tacrolimus and mycophenolate in 14 pts (38%). RESULTS: 36 patients (97%) were evaluable for engraftment. 1 patient died within 30 days due to progressive leukemia. 34/36 patients (95%) engrafted neutrophils and had hematopoietic recovery with 100% cord blood-derived cells. At day 30, of the 29 patients who received a double CBT, 75% had chimerism derived entirely from one donor while 25% had mixed donors chimerism. Neutrophil recovery to ANC >0.5 × 10e9/l occurred after a median of 21 days (range 6–45) and platelet recovery to >20 × 10e9/l after a median of 37 days (range 26–134, N=24; 67%). 32/37 pts (87%) were in CR after transplant with 16 surviving after a median follow-up of 12.1 months. Thirteen patients (36%) developed gr II–IV aGVHD (gr III–IV aGVHD in 5 patients, 14%), and 13 of 32 patients had cGVHD (40%), with the majority experiencing extensive GVHD. 11 patients (29.7%) relapsed after a median of 7 months post transplant and 12 died of nonrelapse causes. Day-100 treatment-related mortality in this heavily pre-treated population was 10%. Overall, causes of death included disease relapse (n=9), infections (n=6), organ failure (n=3), pulmonary hemorrhage (n=1) and GVHD (n=2). CONCLUSIONS: The FMT regimen was sufficiently immunosuppressive to support high rate of engraftment with acceptable TRM in heavily pre-treated adult patients with advanced hematologic malignancies undergoing CBT. These results support further evaluation of this regimen in CBT.

Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies

Blood ◽  
2004 ◽  
Vol 104 (12) ◽  
pp. 3813-3820 ◽  
Author(s):  
Satoshi Takahashi ◽  
Tohru Iseki ◽  
Jun Ooi ◽  
Akira Tomonari ◽  
Kashiya Takasugi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Cord Blood ◽  
Marrow Transplantation ◽  
Cord Blood Transplantation ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Adult Patients ◽  
Transplant Recipients ◽  
Blood Transplantation

Unrelated cord blood transplantation (CBT) has now become more common, but as yet there have been only a few reports on its outcome compared with bone marrow transplantation (BMT), especially for adults. We studied the clinical outcomes of 113 adult patients with hematologic malignancies who received unrelated BM transplants (n = 45) or unrelated CB transplants (n = 68). We analyzed the hematopoietic recovery, rates of graft-versus-host disease (GVHD), risks of transplantation-related mortality (TRM) and relapse, and disease-free survival (DFS) using Cox proportional hazards models. The time from donor search to transplantation was significantly shorter among CB transplant recipients (median, 2 months) than BM transplant recipients (median, 11 months; P < .01). Multivariate analysis demonstrated slow neutrophil (P < .01) and platelet (P < .01) recoveries in CBT patients compared with BMT patients. Despite rapid tapering of immunosuppressants after transplantation and infrequent use of steroids to treat severe acute GVHD, there were no GVHD-related deaths among CB transplant recipients compared with 10 deaths of 24 among BM transplant recipients. Unrelated CBT showed better TRM and DFS results compared with BMT (P = .02 and P < .01, respectively), despite the higher human leukocyte antigen mismatching rate and lower number of infused cells. These data strongly suggest that CBT could be safely and effectively used for adult patients with hematologic malignancies.

scholarly journals Treosulfan-based conditioning is feasible and effective for cord blood recipients: a phase 2 multicenter study

2020 ◽  
Vol 4 (14) ◽  
pp. 3302-3310
Author(s):  
Filippo Milano ◽  
Jonathan A. Gutman ◽  
H. Joachim Deeg ◽  
Eneida R. Nemecek ◽  
Joachim Baumgart ◽  
...  
Keyword(s):  
Cord Blood ◽  
Clinical Outcomes ◽  
Hematopoietic Cell Transplantation ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Hematologic Malignancies ◽  
Phase 2 ◽  
Acute Leukemias ◽  
Blood Transplantation

Abstract Although the use of treosulfan (TREO) in conventional donor hematopoietic cell transplantation (HCT) has been extensively evaluated, its use in cord blood transplantation (CBT) for hematologic malignancies has not been reported. Between March 2009 and October 2019, 130 CBT recipients were enrolled in this prospective multicenter phase 2 study. The conditioning regimen consisted of TREO, fludarabine, and a single fraction of 2 Gy total-body irradiation. Cyclosporine and mycophenolate mofetil were used for graft-versus-host disease prophylaxis. The primary end point was incidence of graft failure (GF), and based on risk of GF, patients were classified as low risk (arm 1, n = 66) and high risk (arm 2, n = 64). The median age was 45 years (range, 0.6-65 years). Disease status included acute leukemias in first complete remission (CR; n = 56), in ≥2 CRs (n = 46), and myelodysplastic (n = 25) and myeloproliferative syndromes (n = 3). Thirty-five patients (27%) had received a prior HCT. One hundred twenty-three patients (95%) engrafted, with neutrophil recovery occurring at a median of 19 days for patients on arm 1 and 20 days for patients on arm 2. The 3-year overall survival, relapse-free survival (RFS), transplant-related mortality, and relapse for the combined groups were 66%, 57%, 18%, and 24%, respectively. Among patients who had a prior HCT, RFS at 3 years was 48%. No significant differences in clinical outcomes were seen between the 2 arms. Our results demonstrate that TREO-based conditioning for CBT recipients is safe and effective in promoting CB engraftment with favorable clinical outcomes. This trial was registered at www.clinicaltrials.gov as #NCT00796068.

scholarly journals Early infections in adult patients undergoing unrelated donor cord blood transplantation

2002 ◽  
Vol 30 (12) ◽  
pp. 937-943 ◽  
Author(s):  
S Saavedra ◽  
GF Sanz ◽  
I Jarque ◽  
F Moscardó ◽  
C Jiménez ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Adult Patients ◽  
Unrelated Donor ◽  
Blood Transplantation

Unrelated Cord Blood Transplantation: Comparison After Single Unit Cord Blood Intrabone Injection and Double Unit Cord Blood Transplantation In Patients with Hematological Malignant Disorders. A Eurocord-EBMT Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 223-223 ◽  
Author(s):  
Vanderson Rocha ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Marina Podestà ◽  
Dolores Caballero ◽  
...  
Keyword(s):  
Cord Blood ◽  
Median Time ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Adult Patients ◽  
Myeloablative Conditioning ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
The Impact

Abstract Abstract 223 The use of single cord blood unit for transplantation in adult patients is limited due to the high risk of graft failure and delayed neutrophil and platelet recoveries. The limited hematopoietic progenitors in UCB grafts and their homing after IV injection, have prompted investigators to study the design of delivering CB grafts directly into the bone marrow (BM) space (IBCBT) or to use double cord blood transplantation (dUCBT) to improve engraftment. To evaluate the impact of IBCBT, we made a retrospective based registry comparison with dUCBT performed in the same time period (2006-2010) and reported to Eurocord-EBMT. We included 87 and 149 patients who received either IBCBT or dUCBT, respectively, after a myeloablative conditioning regimen for malignant disorders. IBCBT was performed in 8 EBMT centers whereas dUCBT was performed in 56 EBMT centers. Majority of patients in both groups had acute leukemia. IBCBT patients were older (p<0.001), more frequently received an autologous graft (p<0.001) and had positive CMV serology (p<0.001), and importantly had more advanced disease at transplantation (p=0.04). Median number of infused (after thawing) nucleated cells injected intrabone was 2.5×107/kg and it was 3.9×107/kg in dUCBT (p<0.001). In 72% of both groups, CB grafts were HLA 4/6 (the highest HLA disparity was taken into consideration in dUCBT). Other differences were regarding GVHD prophylaxis that was based on CSA+MMF in 100% of IBCBT and in 62% of dUCBT cases; ATG was used in all IBCBT and 40% of dUCBT. Median follow-up time was 18 months in IBCBT and 17 months in dUCBT. At day 30, cumulative incidence (CI) of neutrophil recovery (ANC >500) was 83% after IBCBT and 63% after dUCBT, and at day 60, it was 90% in both groups; the median time to reach ANC>500 was 23 and 28 days after IBCBT and after dUCBT (p=0.001) respectively. At Day-180 CI of platelets recovery was 81% after IBCBT and 65% after dUCBT (p<0.001) with a median time of 36 days and 49 respectively (p=0.002). At day 100, CI of acute GVHD (II-IV) was 19% and 47% (p<0.001) and chronic GVHD 34% and 37% respectively (p=NS) respectively. Unadjusted 2 years-CI of NRM and RI were 31% and 23% after IBCBT and 35% and 28% after dUCBT, respectively (p=NS). Unadjusted 2 y-DFS estimation was 47% after IBCBT and 37% after dUCBT (p=NS). In multivariate analysis adjusting for statistical differences between 2 groups (such as status of the disease at transplant, age, CMV, previous transplants, GVHD prophylaxis), recipients of IBCBT had improved DFS (HR: 1.64, p=0.035), faster platelet recovery (HR:2.13, p<0.001) and decreased acute GVHD (HR:0.31; p<0.001) compared to dUCBT recipients. We did not find a cut-off value of number of nucleated cells after IBCBT or dUCBT that could be associated with outcomes after both approaches. In conclusion, both strategies have extended the use of CB transplants to adults in need of cord blood transplantation. Therefore, IBCBT is an option to transplant adult patients with single CB units after myeloablative conditioning regimen and may impact the total costs of cord blood transplantation. Based on these results, intra-bone technique may disclose new transplant potentialities also with other HSC sources. Disclosures: No relevant conflicts of interest to declare.

Irradiation-Based Myeloablative Cord Blood Transplantation for Hematologic Malignancies In Adults.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4583-4583
Author(s):  
Huilan Liu ◽  
Xingbing Wang ◽  
Liangquan Geng ◽  
Kaiyang Ding ◽  
Baolin Tang ◽  
...  
Keyword(s):  
Cord Blood ◽  
Total Dose ◽  
Research Funding ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Hematologic Malignancies ◽  
Adult Patients ◽  
Pcr Analysis ◽  
Myeloablative Conditioning ◽  
Blood Transplantation

Abstract Abstract 4583 We retrospectively analyzed of the engraftment, Transplant-related complications and survival after unrelated cord blood transplantation (UCBT) using irradiation-based myeloablative conditioning in adult with hematologic malignancies. Between September 2006 and June 2010, 29 consecutive adult patients with hematological malignancies were treated with UCBT, Thirteen of them were advanced-stage disease and 11 of them were high risk or refractory disease. All patients received four fractionated 12 Gy TBI, total dose 12 g/m2 cytarabine and total dose 120 mg/kg cyclophosphamide as myeloablative conditioning. The median age was 21 years; the median weight was 57 kg. Double or multiple UCB grafts were used for 17 patients, while single UCB graft for 12 patients. the median number of nucleated cells was 3.83×107/kg and 5.25×107/kg. All patients were given a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. All patients obtained engraftment. Median time to neutrophil≥0.5×109/L was 20 days (range 14–37) and platelet engraftment in 25 patients (≥20×109/L) was 35 days (range 25–49). Chimerism was assessed by PCR analysis of short tandem repeat (STR) sequences on whole blood or bone marrow weekly in cases who were fully donor chimeric from 7 days to 21 days after transplantation. 16 cases developed acute GVHD, more than grade II in three cases. Six of twenty-four patients who survived more than 100 days developed limited chronic GVHD.17 cases were alive and in hematologic remission at a median follow-up of 504 days (range 49 ~ 1245). The probability of over survival at 3 years was 58.6%. Five cases relapsed. Nine of twelve cases died of transplant related complications and infection. These results suggest that UCBT after TBI-based myeloablative conditioning could be safely and effectively used for adult patients with hematologic malignancies. Disclosures: Sun: the Fund of the Key Medical Project of Anhui Provincial healthy department (2010A005): Research Funding; the Clinical Technology foundation of Anhui Provincial healthy department (2008A011): Research Funding; the Fund of Anhui Provincial “115” Industrial Innovation Program: Research Funding.

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