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 (>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<0.01) and administration of granulocyte colony stimulating factor after CBT (p<0.01) were associated with earlier neutrophil engraftment. Preconditioning with TBI (p<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<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<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.

Outcome and Prognostic Factors after Unrelated Donor Umbilical Cord Blood Transplantation in Adult Patients with Hematologic Malignancies Transplanted in Early Disease Stages.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2149-2149 ◽  
Author(s):  
Guillermo Sanz ◽  
Ignacio Lorenzo ◽  
Federico Moscardo ◽  
Dolores Planelles ◽  
Luis Larrea ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Hematologic Malignancies ◽  
Unrelated Donor ◽  
Early Disease ◽  
Blood Transplantation ◽  
Cd34 Cells ◽  
Grade Ii ◽  
Disease Stages

Abstract Stage of the disease at transplant is critical for outcome after unrelated donor umbilical cord blood transplantation (UD-UCBT). The results of UD-UCBT in adults transplanted early in the course of their disease are unclear. Thus, UD-UCBT remains as the last resort for most patients. The major aim of this report was to study the outcome of a series of adult patients with hematologic malignancies undergoing UD-UCBT early in the course of their disease in a single institution. From May 1997 to May 2004, 40 patients in early disease stages underwent UD-UCBT. All patients received thiotepa, busulfan (orally in 29, intravenously in 11), cyclophosphamide, and antithymocyte globulin (Lymphoglobulin in 24 and Thymoglobulin in 16) as conditioning, cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis, and filgrastim to fasten engraftment. Diagnosis were chronic myeloid leukemia in chronic phase in 14 cases, high-risk acute lymphoblastic leukemia in 14 (12 in CR1, 1 in CR2, and 1 in CR3), high-risk acute myeloblastic leukemia in 8 (7 in CR1 and 1 in CR2), and high-risk myelodysplastic syndrome in 4 (3 untreated and 1 in CR1). Median age was 27 years (range, 16–46). The degree of HLA match (HLA-A and -B by serology and -DRB1 by high-resolution DNA typing) was 6/6 in 2 (5%), 5/6 in 18 (45%), and 4/6 in 20 cases (50%). The median number of nucleated and CD34+ cells infused was 1.8 x 107/kg (range, 0.9–4) and 0.8 x 105/kg (range, 0.1–5.7) respectively. Median time to PMN above 0.5 x 109/L and to platelets above 20 x 109/L was 22 days (range, 13–44) and 69 days (range, 32–188), and the cumulative incidence of myeloid and platelet engraftment was 90% (95% CI, 81–99%) and 70% (95% CI, 57–86%), respectively. Time to myeloid engraftment showed a direct relationship with the number of CFU-GM and CD34 cells cryopreserved (P = .02 and .01 respectively) and infused (P = .0001 and .0004 respectively). Platelet engraftment was faster in patients receiving grafts with a higher number of CFU-GM (P = .005) and CD34+ cells (P = .04), in those receiving Thymoglobulin (P = .02) and in those not developing acute GVHD above grade II (P = .04). Eight patients (20%) developed acute GVHD above grade II, and 9 of 25 patients at risk had extensive chronic GVHD. Patients receiving Thymoglobulin had a lower risk of acute GVHD (P = .0003). With a median follow-up of 33 months (range, 3–87), the probability of disease-free survival (DFS) at 3 years was 48% (95% CI, 30–66%) and was related directly to age (P = .004) and inversely to the development of acute GVHD above grade II (P = .004). The probability of DFS at 3 years was 66 % for patients younger than 31 years and 54% for those not developing acute GVHD above grade II. Cell dose, degree of HLA mismatch, and diagnosis did not clearly influence DFS. These results compare to those obtained after matched unrelated donor bone marrow transplantation, and suggest that UD-UCBT is a reasonable first-line option for adults with hematologic malignancies requiring transplantation and lacking a HLA-matched sibling donor.

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.

Impact of Acute GVHD on Immune Reconstitution after Cord Blood Transplantation in Adult.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 984-984 ◽  
Author(s):  
Tokiko Nagamura-Inoue ◽  
Satoshi Takahashi ◽  
Jun Ooi ◽  
Akira Tomonari ◽  
Toru Iseki ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cord Blood ◽  
Nk Cells ◽  
Immune Reconstitution ◽  
Cord Blood Transplantation ◽  
Adult Patients ◽  
Blood Transplantation ◽  
Cd34 Cells ◽  
Grade Ii

Abstract BACKGROUND: Immune reconstitution following unrelated cord blood transplantation (UCBT) in adult patients is of great concern because of immaturity of cord blood immunological cells. STUDY DESIGN AND METHODS: Twenty-six adult patients (15 to 58 year-old) with hematological malignancies, who underwent UCBT and sustained engraftment were enrolled in this study. Infused number of immunological cells in thawed CB units including T cells (CD3+), B cells (CD19+), NK cells (CD3-CD56+), monocytes (CD14+) and also CD34 + cells was analysed using bead-contained TRUCOUNT tube (BD, CA). Dead cells after thawing were excluded by gating out with 7AAD dye. Immune reconstitution was analysed every 30 days by 120 days after CBT. Four-colour FACS Caliber and TRUCOUNT tube were utilized to calculate the absolute number of immune cells concentration in blood after UCBT. We put strict volume of 50μl fresh unmanipulated blood in each TRUCOUNT tube. RESULTS: Thawed-transplanted NC 2.3±x107/kg, CD34 was 0.72±0.3x105/kg (4.1x106 total), T cells; 3.1±1.6x106/kg with CD4/8 ratio of 3.2±2.0, B cells; 1.2±0.5x106/kg, NK cells; 1.0±0.5x106/kg and monocytes; 1.6±0.6x106/kg. There were no correlations between infused CD34+ cells number and T, B, NK and monocytes numbers. Monocytes increased in blood rapidly after CBT at 30 days, then, declined to the normal value. NK cells was recovered in the early after CBT and then did not so change in number from 30 to 120 days after CBT, while T cells increased time dependent manner, and B cells appeared late but influenced by acute GVHD grade. Within 120 days after CBT, T cells showed also CD4+dominant in most cases with relatively high CD25+CD4+ regulatory T (rT) cells compared to normal control. The patients with grade II to IV aGVHD showed significantly higher number of rT cells on 30 days (P<0.05) compared to those with grade 0–I aGVHD. On day 30, the number of rT cells showed 7.7±5.9/μl in grade 0–I aGVHD and 19.4±13.3/ μl in grade II–IV. The patients with grade II to IV aGVHD showed significant delayed recovery of B cells on 90 days after CBT compared to those with 0–I aGVHD (P<0.001). CONCLUSION: aGVHD in adult patients may influence on the number of regulatory T cells in the early period after UCBT and delayed recovery of B cells.

Double Cord Blood Transplantation in Bone Marrow Failure Syndromes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2018-2018
Author(s):  
Regis Peffault de Latour ◽  
Vanderson Rocha ◽  
Marie Robin ◽  
Celso A. Rodrigues ◽  
Delphine Rea ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Bone Marrow Failure ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Bone Marrow Failure Syndromes ◽  
Cord Blood Unit ◽  
Grade Ii

Abstract The outcome of severe aplastic anemia, refractory to immunosuppressive therapy or observed in case of Fanconi anemia (FA), is usually poor in the absence of Hematopoietic Stem Cell Transplantation (HSCT). Umbilical cord blood is an alternative stem cell source for patients without matched related or unrelated donors. However, single cord blood unit is associated with high transplant related mortality due to the low cell dose infused in previous highly transfused patients. We have driven the hypothesis that double cord blood transplantation (dCBT) could circumvent the cell dose problem. For the purpose of this study, we have studied 13 patients with bone marrow failure syndromes given 2 partially matched dCBT from 2004 to 2007. The diagnoses were FA (n=9), SAA (n=4) and PNH (n=1). Among those patients, 5 (39%) received a dCBT as a rescue of previous rejected transplants (2 SAA and 3 FA). All patients received a fludarabine-based regimen, with TBI (2 Gy) for 4 patients. Cord blood units were a 4/6 or 5/6 HLA A, B and DR match with the patient except one which was 3/6. Graft versus host disease (GVHD) prophylaxis consisted in CSA+MMF. Steroids were given from day 7 to day 14 and stopped in case of no GVHD. Five male (39%) and 8 female (61%) with a median age of 16 years (range 7–31) were treated. The cell doses infused were a median of 5.0 × 107 NC/Kg (4–9) and 5.3 × 105 CD34+ cells/Kg (2–8). Graft rejection was seen in 5 patients (2 previously allotransplanted). Among those patients, one displayed a temporary mixed chimerism before rejection and another presented an autologous reconstitution. Among the remaining 8 patients, the median time to an absolute neutrophils count &gt; 500 was 25 days (range 14–42) and the median time to a platelet count &gt; 20,000 was 39 days. In these last patients, we observed a complete donor chimerism with one cord blood unit during 100 days after dCBT. Acute GVHD grade II–III was scored in 9 patients (69%) (7 grade II, 2 grade III). No patients presented acute GVHD grade IV. Four patients out of 8 developed Chronic GVHD (3 limited and 1 extensive). Four patients died (1 GVHD, 2 fungal infection, 1 thrombotic microangiopathy). With a median follow-up of 13 months (range 1 to 19 months), the overall survival was 55% (±15%) for all patients. The median survival of patients who were transplanted twice was 50% (±25%). In conclusion, dCBT seems to be an option to treat patients with bone marrow failure syndromes and without a suitable compatible HLA donor. Those results need to be established on a large number of patients to warrant the inclusion of dCBT in the treatment strategy of diseases with high risk of rejection.

Double Cord Blood Transplantation in Hematologic Malignancy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4426-4426
Author(s):  
Zimin Sun ◽  
Huilan Liu ◽  
Xingbing Wang ◽  
Liangquan Geng ◽  
Miao Zhou ◽  
...  
Keyword(s):  
Cord Blood ◽  
Median Time ◽  
Acute Gvhd ◽  
Hematologic Malignancy ◽  
Cord Blood Transplantation ◽  
Major Barrier ◽  
Promising Alternative ◽  
Cell Dose ◽  
Blood Transplantation ◽  
Cd34 Cells

Abstract Purpose: Cord blood transplantation (CBT) is a promising alternative means of allogeneic stem cell transplantation. However, the limited cell dose of single umbilical cord blood (UCB) unit has been a major barrier to its more widespread use. With the hypothesis that double CBT (dCBT) could circumvent the cell dose problem, we analyzed the early engraftment kinetics in 10 hematologic malignancy patients given 2 partially matched dCBT. Methods: Patients were eligible for dCBT when a single 4-6/6 HLAmatched UCB unit with adequate nucleated cell dose is unavailable. From November 2005 to June 2008, 10 patients (3 male and 7 female) with a median age of 22 years (range 10–37) and a median weight of 55kg (range 31–70 kg) were recruited, including 4 ALL, 3 AML, and 3 CML. All patients received myeloablative conditioning (Flu/Cy/TBI for 6 patients, BU/CY2 for 2 and BU/CY2/BCNU for one). Graft versus host disease (GVHD) prophylaxis was CSA+MMF. They received two units with at least one 5/6 HLA-match unit. The median combined graft nucleated cell (NC) dose was 3.98°Á107/kg (range 3.51–7.70°Á107 NC/kg), and the median CD34+ cell dose was 2.37°Á105/Kg (range, 0.94–5.23°Á105/kg). Results: Eight patients (80%) had sustained hematopoietiec recovery. The median time to an absolute neutrophils count &gt; 500 was 18 days (14'C29) and the median time to a platelet count &gt; 20,000 was 34 days (27–46). Among those patients, one displayed the engraftment derived from both donors for six months until her death. The both units were 6/6 HLA matched the recipient, and had similar number of nucleated cells, CD34+ cells and CD3+ cells. The sustained hematopoiesis was derived from a single dominant one in the remianing 7 pateints. By STR-PCR, the median values of the percentage of the dominant unit was 80%(30–100%)at post-transplantatiom day 7, and they all achieve complete donor chimerism at day 28. The median infused cell dose of the predominating unit was 2.6°Á107 NC/Kg (range 1.3–4.45 °Á107/kg), 1.56°Á105 CD34+/Kg, (range 0.47–4.00°Á105/kg), and 0.53°Á107CD3+/Kg (range 0.34–2.59°Á107/kg), in contrast to 1.46°Á107 NC/Kg (range 0.96–6.09°Á107/kg), 0.87°Á105CD34+/Kg (range 0.20–2.55°Á105/kg), and 0.52°Á107CD3+/Kg (range 0.12–1.69°Á107/kg) in the nonsustained unit. When analyzed separately, units with high numbers of total nucleated cells, CD34+ cells or CD3+ cells dominate the engraftments in 4 partially overlapping patients. Only 3 of the 7 patients with donor engraftment received 2 UCB units with different degrees of HLA disparity. Of these, the better HLA-matched unit to the recipient predominated in 1 patients, while lesser matched units engrafted over the better matched units in 2 patients. Acute GVHD grade = 1 \* ROMAN ICIII was scored in 3 patients (37.5%) (1 grade = 1 \* ROMAN I, 1 grade II and 1 grade III). No patients presented acute GVHD grade IV. Three patients died (2 fungal infection, 1 serious hepatitis). Conclusions: Two units CBT is a safe and effective alternative option for hematologic malignancy treatment. Generally, hematopoiesis will be dominated by only one unit in patient received dCBT and it may occur as early as 7days after transplantation. However, the mechanism to determine this dominancy remains elusive, as nucleated cell dose, CD34+ cell dose, CD3+ graft cell dose and HLA match all failed to predict the predominant unit. Table 1 Characteistics of dominant and non-dominant cord blood units patients No1 No2 No3 No4 No5 No6 No7 TNC (°Á107/Kg) Dominant unit 1.3 2.7 3.79 2.6 4.45 2.3 2.48 Non-dominant unit 2.3 1.3 3.7 1.3 6.09 0.96 1.46 CD34 (°Á105/Kg) Dominant unit 1.56 0.77 1.82 1.85 4 0.74 0.47 Non-dominant unit 1.16 1.45 2.55 0.25 0.87 0.2 0.83 CD3 (°Á107/Kg) Dominant unit 0.53 0.34 0.74 2.59 0.35 0.42 0.83 Non-dominant unit 0.4 0.12 0.56 1.69 0.52 0.49 0.96 HLA mismatch Dominant unit 1/6 1/6 0/6 1/6 1/6 1/6 1/6

scholarly journals Low Lymphocyte Count at Day 30 after Single Cord Blood Transplantation Had Negative Impact on Survival, Because of Higher NRM Rate

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4482-4482
Author(s):  
Mitsuhiro Yuasa ◽  
Kosei Kageyama ◽  
Daisuke Kaji ◽  
Yuki Taya ◽  
Shinsuke Takagi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cord Blood ◽  
Negative Impact ◽  
Cord Blood Transplantation ◽  
Disease Status ◽  
Underlying Disease ◽  
Median Number ◽  
Cell Dose ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis

&lt;Introduction&gt; Delayed immune reconstitution after allogeneic transplantation increases the risk of treatment-related mortality, and chronic GVHD. Previous reports showed that absolute lymphocyte count at day 30 (ALC30) was a significant prognostic factor of transplantation, and lower numbers of total CD4+ T cells and naïve CD4+ T cells in particular were associated significantly with higher mortality. However, there is little knowledge about the factors associated with low lymphocyte recovery, especially in cord blood transplantation (CBT). The cut-off value of lymphocyte recovery for statistical significance has not been determined yet. &lt;Methods&gt; We retrospectively analyzed the outcome of 579 consecutive patients who underwent single cord blood transplantation (CBT) for the first time at Toranomon Hospital between January 2011 and 2018. Patients with active infection at transplantation (n=40), in poor ECOG PS (3 or more) (n=36), or lacked information about CT before CBT (n=1) were excluded from this study. &lt;Results&gt; Five hundred and two patients (n=317 male; n=185 female) were included in this study. The median age at transplantation was 57 years (range, 16-77), with a median HCT-CI score of 2 (0-10). Underlying diseases were AML (307), MDS (43), MPN (20), ALL (50), mature lymphoid malignancies (54), and others (28). Median spleen index (SI) before transplantation was 60.2 (16.5-319.7). Three hundred and ninety eight patients (79%) were not in remission at transplant. MAC regimens were selected in 400 (80%). TAC alone was used in 132 (26%) as GVHD prophylaxis. Median number of TNC and CD34+ cells infused were 2.62 (1.57-6.85) x 107/kg and 0.86 (0.29-3.77) x 105/kg, respectively. 194 (39%) were positive for anti-HLA antibodies, but none had donor-specific. With a median follow-up of 32 (range, 3-99) months, cumulative incidence of neutrophil engraftment (NE), the 3-year probabilities of overall survival (OS), relapse rate (RR) and non-relapse mortality (NRM) for entire population were 92.8%, 40.6%, 23.5%, and 35.3%, respectively. Underlying disease (myeloid malignancy), disease status at SCT (non-CR), poor PS (PS=2), GVHD prophylaxis (TAC+MMF), low CD34-positive cell dose (&lt;0.8 x 105/kg), and splenomegary (SI ≥ 40) were significantly associated with inferior NE in multivariate analysis. Disease status at SCT (non-CR), poor PS (PS=2), Higher HCT-CI (PS ≥ 3), and GVHD prophylaxis (TAC+MMF) were significantly associated with higher NRM in multivariate analysis. We analyzed the relationship between ALC30 and transplantation outcome. Median number of ALC30 was 231 (3.5-1503), and the 25th percentile was 144. We divided the cohort into two groups, ALC30 low group (&lt;150, n=123), ALC30 high group (≥150, n=346). High number of ALC30 (≥150) was associated with better survival (48.1% vs. 29.5%, p &lt; 0.01) and lower NRM (26.9% vs. 41.9%, p &lt; 0.01) due to reduced incidence of lethal infection (7.1% and 23.4% of total death in ALC30 high and low, respectively, p &lt; 0.01), but was not associated with RR (25.5% vs. 25.1%, p = 0.59). High ALC30 (≥150), as well as younger age (&lt;60), underlying disease (myeloid malignancy), better PS (0-1), and disease status at SCT (CR) showed a superior OS in multivariate analysis. We then assessed factors associated with ALC30, and higher infused dose of CD34-positive cells was the only factor associated with high ALC30, (p=0.03, t-test). Other factors, such as infused TNC dose, type of conditioning, or GVHD prophylaxis did not show significant association with ALC30. &lt;Conclusion&gt; This retrospective study demonstrated that low ALC30 after CBT had negative impact on survival because of higher NRM rate. High CD34-positive cell dose was the only factor associated with high ALC30. Not CD34-positive cell dose, but ALC30 had significant impact on OS in multivariate analysis, so we need to take lymphocyte recovery into account, in an attempt to improve transplantation outcome. Figure Disclosures No relevant conflicts of interest to declare.

Reduced-Intensity Unrelated Cord Blood Transplantation in Adult – a Single Center Analysis of 318 Transplants.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1970-1970
Author(s):  
Shuichi Taniguchi ◽  
Atsushi Wake ◽  
Kazuhiro Masuoka ◽  
Naoyuki Uchida ◽  
Naofumi Matsuno ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Lymphoblastic Leukemia ◽  
Cord Blood Transplantation ◽  
Disease Status ◽  
Tumor Control ◽  
High Grade Fever ◽  
Blood Transplantation ◽  
Standard Risk ◽  
Reduced Intensity

Abstract Objective: Cord blood is widely used as a third possible stem cell source for allogeneic transplantation following bone marrow and peripheral blood. CBT has unique characteristics such as allowing 2 loci mismatch and emergency use or ready to use transplantation. Reduced-intensity transplantation also has been widely accepted to offer opportunities for allogeneic transplant for older and poor overall status patients. We previously showed the feasibility of reduced-intensity cord blood transplantation (RI-CBT) in 30 patients with advanced hematological diseases. Then performed more than 300 time RI-CBT to those whom needed urgent transplantation without suitable HLA matched donors. Methods: We retrospectively analyzed medical records of 318 times and 287 cases of RI-CBT from 1/1/2004 to 5/7/2008 in Toranomon Hospital. Disease distribution of 287 studied patients was as follows; acute myeloblastic leukemia/myelodysplastic syndrome was 136 cases, malignant lymphoma 58, acute lymphoblastic leukemia 42, adult T cell leukemia/lymphoma 25, severe aplastic anemia 8 and others 18. A mean age was 56 ranging from 19 to 79 years old. The number of high risk and standard status patients were 243 and 44, respectively. High risk disease status is defined as residual uncontrolable tumor cells despite of chemotherapy such as primary refractory and beyond CR1 and standard risk is as in remission in a meaning of tumor control. MDS and SAA patients who need frequent transfusions and intensive care for infection are defined as standard risk. Preparative regimen mainly composed of fludarabine 25 mg/m2 on days -7 to -3, melphalan 80 mg/m2 on day -2, and 4 Gy total body irradiation on day -1. Some patients were contiditioned with iv-busulfan without TBI. Graft-versus- host disease prophylaxis was composed of cyclosporine or tacrolimus alone. Results: We analyzed the association of various factors on engraftment in possible 158 patients. Eighty eight % (95% CI, 83%–93%) of patients were engrafted on a median days of 20 (range, 11–55 days) after transplant. Multivariate analysis revealed 5 to 6 antigen match in GVH direction was a significant independent factor for engraftment as well as CD34 dose, while HLA in HVG direction did not significantly influence on engraftment. Three-year estimated overall survival (OS) in total 287 cases was 39.6% (95% CI: 33.5–45.8%). Standard risk patients (n=44) showed 3-year OS of 53.8% (95% CI: 38.3–69.2%) and high risk (n=243) was 26.3% (95% CI:20.2–32.5%). Tacrolimus GVHD prophylaxis group (n=159) had superior 3y-OS of 33.8%(95% CI: 25.9–41.8) to cyclosporine alone with 3yOS of 22.4 % (95% CI: 14.2–30.7). We previously reported pre-engraftment immune reaction characterized by high-grade fever and weight gain and developed on a median of day 9. More intensive immune suppression after RI-CBT using tacrolimus decreased the incidence and severity of PIR and increased OS. Conclusion: RI-CBT is a feasible approach even for relatively aged patient population (Mean age=56) with advanced hematological malignancies.

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