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.

Outcomes of Unrelated Umbilical Cord Blood Transplantation Using a Conditioning Regimen of TBI/Ara-c/CY without ATG for Adolescent and Adults Patients with High-Risk Hematologic Malignancies

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4525-4525
Author(s):  
Zimin Sun ◽  
Huilan Liu ◽  
Liangquan Geng ◽  
Xingbing Wang ◽  
Kaiyang Ding ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Adult Patients ◽  
Myeloablative Conditioning ◽  
Blood Transplantation

Abstract Abstract 4525 To retrospectively analyze the curative efficacy of umbilical cord blood transplantation (UCBT) using total body irradiation (TBI)-based myeloablative conditioning regimen without antithymocyte globulin (TBI/Ara-c/CY w/o ATG) in adolescent and adult patients with high-risk hematological malignancies. Outcomes of forty-five consecutive adolescent and adult patients with high-risk hematological malignancies treated with TBI-based myeloablative UCBT without ATG in a single center between September 2006 and February 2012 were retrospectively analyzed. The conditioning regimen included TBI/Ara-c/CY:TBI 12GY (four fractionated) + Ara-C 8g/m2 (two days fractionated) + CY 120mg/kg (two days fractionated), and rhG-CSF was administered for myeloid leukemia by continuous infusion at a dose of 5μg·kg−1·d−1. Infusion of G-CSF was started 24 hours before the first dose of Ara-C and stopped at the completion of the last dose. The patients included 31 males and 14 females, with a median age of 21 years (range: 14–40) and a median weight of 58 kg (range: 42–76). Of those, 17 patients (37.8%) had advanced disease. Double UCB grafts were used for 16 patients, while single UCB graft was used for 29 patients. The median number of nucleated cells infused was 3.57 (1.94∼6.76)×107/kg and the median CD34+cells infused was 2.11 (0.71∼4.95)×105/kg. All patients received a combination of cyclosporine (CSA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. All patients successfully engrafted. The median times to neutrophil (ANC≥0.5×109/L) and platelet (PLT PLT≥20×109/L) recovery were 19 days (range: 13–35 days) and 36 days (range: 24–90 days) respectively after transplantation in 40 evaluable patients. Acute GVHD occurred in 21 patients and the cumulative incidences of gradeII-‡W and grade III-‡W acute GVHD were 24.4% and 11.1%, respectively. Chronic GVHD occurred in five of 40 evaluable patients (12.5%). Of the 45 patients, 9 (20%) had relapse. After a median follow-up of 25.1 months (range: 6–65.1) among survivors, treatment-related mortality (TRM) within 100 days and within one year was 8.9% and 24.4%, respectively. The main causes of death were pneumonia and severe acute GVHD. The probability of three-year disease-free survival and overall survival (OS) was 53.3% and 57.8%, respectively. The TBI/Ara-c/CY myeloablative conditioning regimen has been well tolerated by patients at our institution and seems to be able to establish sustained donor cell engraftment and decrease the risk of transplant-related death. For high risk patients and patients with advanced disease, this conditioning regimen could reduce relapse and chronic GVHD, indicating the feasibility of TBI/Ara-c/CY as a conditioning regimen for CBT in adolescent and adult patients with hematologic malignancies. Disclosures: Sun: Key Scientific and Technological Project of Anhui province “Twelfth Five-Year Plan” (11010402164): Research Funding; the Fund of the Key Medical Project of Anhui Provincial Healthy Department (2010A005): Research Funding; Anhui Provincial “115” Industrial Innovation Program (2009): Research Funding.

Preliminary Results of Combined Haploidentical-Cord Blood Transplantation for Patients Lacking HLA Identical Donors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3015-3015 ◽  
Author(s):  
Elizabeth Shima Rich ◽  
Andrew Artz ◽  
Theodore Karrison ◽  
Amittha Wickrema ◽  
Loren Joseph ◽  
...  
Keyword(s):  
Cord Blood ◽  
Median Time ◽  
Interstitial Pneumonitis ◽  
Bone Marrow Cells ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
Total Body

Abstract Background: Many patients (pts), particularly minorities, lack matched unrelated donors. Mismatched cord blood (CB) transplantation causes less graft versus host disease (GVHD), but is associated with delayed hematopoietic recovery. We studied an alternative donor regimen using T-cell depleted haploidentical stem cells and unrelated CB pioneered by Magro et al. (Haematologica2006;91:640–8) to confirm engraftment with acceptable rates of GVHD. Patients and Methods: We enrolled 15 pts (7 AML, 1 ALL, 2 MDS, 1 CML, 3 NHL, 1 severe aplastic anemia) lacking HLA identical donors. The median age was 28 years (range, 4–66) and median weight was 75 kg (range, 14–124). Twelve pts had active disease at transplant; 2 had prior autologous transplants. Eight pts were Caucasian; 7 other race or ethnicity. The haploidentical donor was the mother in 3; father in 1; child in 4; sibling in 5; and half-sibling in 2 cases. The median haploidentical CD34+ dose was 2.41 × 106/kg (range, 1.25–6.26); CD3+ cells were 0.8 × 104/kg (range, 0.3–1.3). Single unrelated CB units were matched by low resolution at HLA-A and B and high-resolution at DRB1, and matched 6/6 in 1 pt; 5/6 in 7 pts; 4/6 in 6 pts; 3/6 in 1 pt. Median cord total nucleated cells equaled 2.39 × 107/kg (range, 1.07–9.36); CD34+ cells were 0.14 × 106/kg (range, 0.04–0.75). The conditioning regimen for most pts was fludarabine (Flu) (30 mg/m2 × 5 days), thiotepa (5 mg/kg × 2 days), total-body irradiation (TBI) (12 Gy lateral opposed fields), and Thymoglobulin® (rATG) (1.5 mg/kg × 4 days). Five pts unable to tolerate TBI received Flu, melphalan (70 mg/m2 × 2 days), and rATG. GVHD prophylaxis consisted of tacrolimus (Tac) + methylprednisolone or Tac + mycophenolate. Results: Two pts died early (sepsis, CVA). Twelve of the remaining 13 pts engrafted. One pt failed to engraft and died on day (d)36. Median time to ANC &gt;500/mL was 9 days (range, 9–12). Median time to sustained platelets &gt;20,000/mL was 24 days (range, 12–63). Early haploidentical engraftment was replaced by durable engraftment of CB by 100 days. In unfractionated peripheral blood or bone marrow cells, median haploidentical chimerism was 95% (range, 0–100) on d14; 76% (range, 0–93) on d30; 36% (range, 0–83) on d55; 0% (range, 0–42) on d100; and 0% on d180. Median unfractionated cord chimerism was &lt;5% (range, 0–100) on d14; 24% (range, 7–100) on d30; 64% (range, 17–100) on d55; 100% (range, 58–100) on d100; and 100% on d180. In the CD3+ compartment, median haploidentical chimerism was 94% (range, 0–100) on d14; 72% (range, 0–93) on d30; 24% (range, 0–76) on d55; 0% (range, 0–39) on d100; and 0% on d180. Median CD3+ cord chimerism was 6% (range, 0–100) on d14; 28% cord (range, 7–100) on d30; 76% (range, 24–100) on d55; 100% (range, 61–100) on d100; and 100% (range, 90–100) on d180. Four pts died of sepsis. One pt died of VOD; 2 pts who also received TBI developed interstitial pneumonitis, 1 fatal. Two pts relapsed and died. Cumulative d100 treatment-related mortality (TRM) was 44% (95% CI: 22 to 73%). Acute skin GVHD grade I–II occurred in 3 pts. No cases of chronic GVHD developed. Five pts are currently alive and in remission with complete CB chimerism. The median follow up for survivors is 207 days (range, 23–283). The median age of survivors is 27 years (range, 20–67). Conclusions: Combined haploidentical and CB transplantation is a promising strategy for those lacking HLA identical donors - even in the presence of low CB doses - leading to early haploidentical engraftment followed by durable CB predominance by d100. Acute and chronic GVHD are manageable. Complications such as interstitial pneumonitis may be related to the TBI-containing regimen. This donor combination, with further modifications to decrease TRM, warrants further study in pts lacking HLA identical donors.

Unrelated cord blood transplantation for adult patients with de novo acute myeloid leukemia

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 489-491 ◽  
Author(s):  
Jun Ooi ◽  
Tohru Iseki ◽  
Satoshi Takahashi ◽  
Akira Tomonari ◽  
Kashiya Takasugi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cord Blood ◽  
Median Time ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Cord Blood Transplantation ◽  
Adult Patients ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Acute Myeloid

Abstract We report the results of unrelated cord blood transplantation (CBT) for 18 adult patients with de novo acute myeloid leukemia (AML). The median age was 43 years, the median weight was 55.2 kg, and the median number of cryopreserved nucleated cells was 2.51 × 107/kg. Seventeen patients had myeloid reconstitution and the median time to more than 0.5 × 109/L absolute neutrophil count was 23 days. A self-sustained platelet count more than 50 × 109/L was achieved in 16 patients at a median time of 49 days. Acute graft-versus-host disease (GVHD) above grade II occurred in 11 of 17 evaluable patients and chronic GVHD occurred in 14 of 17 evaluable patients. Fourteen patients are alive and free of disease at between 185 and 1332 days after transplantation. The probability of disease-free survival at 2 years was 76.6%. These results suggest that adult AML patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.

Hemophagocytic Syndrome (HPS) Post Reduced Intensity Cord Blood Transplantation (RI-CBT) in Adult Patients with Hematological Diseases.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2743-2743
Author(s):  
Kazuhiro Masuoka ◽  
Shigesaburo Miyakoshi ◽  
Shinsuke Takagi ◽  
Daisuke Kato ◽  
Eiji Kusumi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Risk Factor ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Bone Marrow Examination ◽  
Important Risk Factor ◽  
Adult Patients ◽  
Hematological Diseases ◽  
Gvhd Prophylaxis

Abstract &lt;Introduction&gt; HPS are rare but often-fatal conditions characterized by an inappropriate and sustained activation of the cellular immune system leading to accumulation of activated macrophages and a cytokine storm. HPS consists of primary and secondary Hemophagocytic Lymphohistiocytosis (HLH). Secondary HLH occurs at any age and the genetic contribution remains uncertain. Clinical features in patients with HLH are fever, cytopenias, liver dysfunction, hepato-splenomegaly, and the presence of hemophagocytosis in the bone marrow as well as other reticuloendothelical tissues. We will report on the hematological abnormalities and the clinical course of 20/152 patients who received RI-CBT and developed secondary HLH in adult patients with hematological disease in early phase after RI-CBT. &lt;Object&gt; The 1st purpose was to investigate the incidence of HLH and pattern of chimerism. The 2nd was to identify the risk factors after UCBT. &lt;Patients and Methods&gt; We reviewed medical records of 152 patients with hematological diseases who had received RI-CBT between January 2002 and April 2005 at Toranomon Hospital, Tokyo, Japan. Diagnosis of HLH was made with the followings; high fever, cytopenias, and hemophagocytic findings in bone marrow examination. Time to event curves were plotted by using the actuarial method of Kaplan-Meier, and differences between curves were analyzed by log-rank tests. The following factors were considered potential predictors of outcomes about 2nd purpose: patient’s age, HLA disparity, infused TNC dose/CD34 dose, disease/disease status at transplantation, GVHD prophylaxis and sepsis which coincided with HLH. All factors were tested for the proportional hazards assumption. &lt;Results&gt; Patient’s median age was 55 years (17–79), Primary diseases consisted of standard (n=31) and advanced (n=121). HLA disparities were 4/6 match (n=123), 5/6 (n=22), and others (n=7). Total nucleated cell/CD34 cell dose were 3.46×10E7/kg (1.6–5.2) and 0.78×10E5/kg (0.1–3.3), respectively. Main conditioning regimen was Fludarabine (125mg/m2) +Melphalan (80mg/m2) or Busulfan (8mg/kg) +TBI 4Gy with cyclospoline (n=89) and tacrolimus (n=63) as GVHD prophylaxis and received single cord blood unit. Twenty patients were diagnosis with HLH and the incidence of HLH was 13% (95%CI; 8–18) and median onset day was 18.5 days (range; 10–29). In patients with sepsis (n=46) and without sepsis (n=106), the incidence of HLH was 28% (95%CI; 15–41) and 7% (95%CI; 3–12), respectively (P&lt;0.0002). All patients who were diagnosis with HLH using bone marrow examination achieved 100% of donor chimerism. In multivariate analysis, the most important risk factor of HLH after RI-CBT was sepsis which coincided with HLH at the same times (p&lt;0.05), while other factors did not influence. &lt;Discussion/Conclusion&gt; HLH is fatal complication after allogeneic peripheral stem cell and unrelated bone marrow transplantation. However in RI-CBT, the incidence would be higher and earlier onset than other sources. The most of HLH patients died by multi-organ failure. In this report the most important risk factor was sepsis which coincided with HLH. Figure Figure

Cord Blood Transplantation from Unrelated Donors for Children with Acute Lymphoblastic Leukemia in Japan: The Impact of Methotrexate on the Clinical Outcome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2023-2023
Author(s):  
Koji Kato ◽  
Ayami Yoshimi ◽  
Etsuro Ito ◽  
Kentaro Oki ◽  
Jun Hara ◽  
...  
Keyword(s):  
Cord Blood ◽  
Acute Gvhd ◽  
Lymphoblastic Leukemia ◽  
Cord Blood Transplantation ◽  
Disease Status ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
Cd34 Cells ◽  
Advanced Stages ◽  
Grade Ii

Abstract Cord blood transplantation (CBT) became one of the important alternatives in allogeneic stem cell transplantation for children with hematological malignancies. We have analyzed the clinical outcomes of CBT for children with acute lymphoblastic leukemia (ALL) in Japan and identified risk factors of transplant outcome, when they had no prior transplant. From 1997 to 2006, total 332 children with ALL have undergone CBT from unrelated donor and 270 of them had no prior transplant. They are 0–15 yrs (median 5) and 4 to 60kg of body weight (median 18). Serological disparities of HLA for graft-versus-host disease (GVHD) direction were 0(n=54), 1(n=168) and 2(n=47), and disease status at transplant were 1st complete remission (CR) (n=120), 2nd CR (n=71), and more advanced stages (n=75). The median number of nucleated cells in cord blood unit was 4.93×107/kg (1.35–24.9), and that of CD34+ cells was 1.53×105/kg (0.17–15.0). As preconditioning, total body irradiation (TBI) was given in 194 patients and methotrexate (MTX) was given as GVHD prophylaxis in 159 patients. The neutrophil engraftment was achieved in 88.5% (95%CI: 84.1–91.8%) of patients and platelet engraftment (&gt;50k) was obtained in 72.6% (95%CI: 66.8–77.7). The incidence of grade II–IV and III–IV acute GVHD was 45.6% (95%CI: 39.5–51.4) and 20.4% (95%CI: 15.8–25.4) respectively. Non-relapse mortality was observed in 22.6% (95%CI: 17.7–27.8) and 35.2% (95%CI: 29.2–41.3) of patients relapsed after CBT. The five year event free survival (EFS) of all patients was 38.1% (95%CI: 34.9–41.3); 47.4%(95%CI: 42.4–52.4) in 1st CR, 45.5%(95%CI: 38.9–52.1) in 2nd CR and 15.2%(95%CI: 10.8–38.9) in more advanced stages, respectively. The multivariate analysis revealed that the larger number of CD34+ cells (p&lt;0.01) and administration of granulocyte colony stimulating factor after CBT (p&lt;0.01) were associated with earlier neutrophil engraftment. Preconditioning with TBI (p&lt;0.01) and absence of MTX (p=0.037) significantly affected the development of grade II-IV acute GVHD. Advanced disease at transplant was the most predominant factor for leukemic relapse (p&lt;0.01). GVHD prophylaxis with MTX (p=0.042), less allele mismatches (p=0.013) and disease status of 1st and 2nd CR at transplant (p&lt;0.01) were significantly associated with better EFS. Our results showed the favorable effect of MTX for the development of acute GVHD and EFS. In conclusion, GVHD prophylaxis including MTX is important in CBT for children with ALL.

Acute Graft-Versus-Host Disease Following Umbilical Cord Blood Transplantation: Retrospective Survey Involving 2015 Japanese Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1070-1070
Author(s):  
Shigesaburo Miyakoshi ◽  
Takuhiro Yamaguchi ◽  
Masahiro Kami ◽  
Tomoko Matsumura ◽  
Koichiro Yuji ◽  
...  
Keyword(s):  
Cord Blood ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Event Free Survival ◽  
Free Survival ◽  
Graft Versus Host ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Acute Graft

Abstract BACKGROUND Limited information is available on incidences and clinical features of acute graft-versus host disease (GVHD) after cord blood transplantation and large-sized researches have been awaited. METHODS We investigated the incidences and clinical features of acute GVHD in 2,015 patients reported to the Japan Cord Blood Bank Network, who underwent cord blood transplantation between June 1997 and August 2006. RESULTS Of 2,015 patients, 1481 patients (73%) achieved neutrophil engraftment at a median of day 22 (range, 6–81). Cumulative incidence of neutrophil recovery at day 100 was 0.74 (95%CI, 0.73–0.76). Of 2015 patients, 708 patients developed grade II-IV acute GVHD: grade II (n=423), grade III (n=237), and grade IV (n=48). The median onset was day 19 (range, 4–190). The cumulative incidences of grade II-IV and III-IV acute GVHD at day 100 were 0.35 (95% CI, 0.33–0.37) and 0.14 (95% CI, 0.12–0.15), respectively. Skin and gastrointestinal acute GVHD was documented in 1,006 and 405 patients, respectively, whereas liver GVHD was diagnosed in 149 patients. Multivariate analysis identified the following predictors of grade II-IV acute GVHD: the number of infused nucleated cells, transplantation from female donors to female recipients, TBI-containing preparative regimens, methotrexate-containing GVHD prophylaxis, and tacrolimus-based GVHD prophylaxis. Overall survival rates at three years of patients with grade 0-I, II and III-IV GVHD who survived 100 days or longer were 0.58 (95%CI, 0.53–0.63), 0.61 (95% CI, 0.54–0.67) and 0.40 (95%CI, 0.31–0.49), respectively. CONCLUSIONS Acute GVHD following cord blood transplantation is mild and has graft-versus malignancy effects. Probability of event free survival after cord blood tranplantation in the patients with grade 0-I, II and III-IV who survived 100 days or longer Event - free survival of the patients with grade 0-I, II and III-IV GVHD who survived 100 days or longer was 0.54 (95% CI, 0.49–0.59), 0.58 (95%CI, 0.52–0.65) and 0.41 (95%CI, 0.32–0.49),respectively,3 years after transplantation. Probability of event free survival after cord blood tranplantation in the patients with grade 0-I, II and III-IV who survived 100 days or longer Event - free survival of the patients with grade 0-I, II and III-IV GVHD who survived 100 days or longer was 0.54 (95% CI, 0.49–0.59), 0.58 (95%CI, 0.52–0.65) and 0.41 (95%CI, 0.32–0.49),respectively,3 years after transplantation.

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 &gt;0.5 × 10e9/l occurred after a median of 21 days (range 6–45) and platelet recovery to &gt;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.

The Impact of HLA Haplotype Matching for Mismatched Cord Blood Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1206-1206
Author(s):  
Satoshi Takahashi ◽  
Jun Ooi ◽  
Nobuhiro Tsukada ◽  
Seiko Kato ◽  
Aki Sato ◽  
...  
Keyword(s):  
Cord Blood ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Graft Function ◽  
Matched Pair ◽  
Control Group ◽  
Graft Versus Host ◽  
Matched Group ◽  
Blood Transplantation ◽  
The Impact

Abstract Abstract 1206 Poster Board I-228 [Study purpose] With the increased number of cord blood transplantation (CBT) for adults, more human leukocyte antigen (HLA)-mismatched grafts are selected as alternative donor. In Japan, we have performed more than 5,500 CBT and almost two-third of them has been using 2-loci HLA-mismatched grafts. Slow engraftment and high risk of graft failure should be solved to improve the clinical results. In general, the degree of HLA disparity is known to be associated with risks of poor graft function and of graft-versus-host disease (GVHD). On the other hand, those risks of transplant-related complications are not equivalent even in the donor-recipient pairs who have same number of mismatched HLA antigens. There might be “haplotype matching effect” because novel undetected major histocompatiblility antigen (MHC) resident variation encoded on HLA haplotypes and those mismatching could be responsible for post-transplant risks. In this study, we have analyzed the impact of HLA haplotype matching in HLA-mismatched CBT using the same method in the single institute. [Patients and Methods] We studied the clinical outcomes of 149 consecutive adult patients who received unrelated CBT between August 1998 and June 2009 in the institute of medical Science, University of Tokyo. Patients received previous allogeneic tranplants were excluded from this study. All patients received myeloablative regimens including 12 Gy of total body irradiation, cyclosporine plus short term methotraxate for GVHD prophylaxis and almost the same supportive care. By low-resolution typing method for HLA-A, -B and –DR loci, 9 patients received matched grafts, 46 received 1 antigen-mismatched and 94 received 2 antigens-mismatched grafts in the host-versus-graft (HvG) direction. In the graft-versus-host (GvH) direction, 7 patients received matched grafts, 51 received 1 antigen-mismatched and 91 received 2 antigens-mismatched grafts. When we looked at the maximum number of mismatched antigens for both directions, 38 patients received 1 antigen-mismatched and 111 received 2 antigens-mismatched grafts respectively, but there was no matched pair. Common haplotypes in Japanese population were referred from the 11th International Histocompatibility Workshop and other previous reports. Median numbers of leukocytes and CD34+ progenitor cells before freezing of cord blood grafts were 2.4×107/kg and 0.9×105/kg, respectively. Median follow-up was 39 months. We evaluated the impact of haplotype matching on cumulative incidences of hematopoietic recovery, of GVHD, of relapse and of non-relapse mortality (NRM) using the Pepe and Mori's test. Estimates of overall survival were calculated using the Kaplan-Meier method and analyzed by the log-rank test. [Results] Thirty (11 of 38 one antigen-mismatched and 19 of 111 two antigens-mismatched) among all 149 pairs were defined as the haplotype-matched pairs sharing same haplotypes in both grafts and recipients. The age, sex, cytomegalovirus serological status, diagnosis, risk of the disease at the transplant, numbers of total nucleated cells and CD34+ cells at the cryopreserved were not significantly different between both groups with and without matched haplotypes. Among the 1 antigen-mismatched pairs in the HvG direction, early engraftment of neutrophil after CBT occurred in haplotype-matched group compared with control group (median: 20.5 days versus 23 days, P=0.01). The haplotype matched group had better platelet engraftment in the 1 antigen-mismatched pairs (cumulative incidence on day 120: 86% versus 62%; median: 41 days versus 53 days), but this is not significant (P=0.29). Such correlation between engraftment and haplotype matching was not observed in 2 antigens-mismatched pairs. The cumulative incidences of grades II to IV acute GVHD were not significantly different between haplotype matched and control groups, however, those of grades III and IV in patients with matched-haplotype tended to be lower among 1 antigen-mismatched pairs in GvH direction (P=0.10) and were significantly lower among 2 antigens-mismatched pairs (P=0.02). Those haplotype matching effects were not observed in survival rates, cumulative incidences of relapse and NRM among any HLA mismatched pairs. [Conclusion] Those data suggest that untyped variation carried on the HLA haplotytpe might be better to be matched and the haplotype matching might effect on better engraftment and lower risk of sever acute GVHD after HLA-mismatched CBT. Disclosures: No relevant conflicts of interest to declare.

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