scholarly journals High-Dose Intravenous Immunoglobulin and Immunosuppressive Therapy Have Therapeutic Potential for Non-Infectious Myelopathy and Peripheral Neuropathy Following Cord Blood Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3390-3390
Author(s):  
Michiho Ebihara ◽  
Shinsuke Takagi ◽  
Yoshikazu Uesaka ◽  
Takashi Mitsuki ◽  
Mitsuhiro Yuasa ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Cord Blood ◽  
Immunosuppressive Therapy ◽  
Intravenous Immunoglobulin ◽  
Protein Level ◽  
Acute Gvhd ◽  
Neurological Symptoms ◽  
High Dose ◽  
Blood Transplantation ◽  
Toranomon Hospital

Abstract BACKGROUND: We previously reported higher incidence of central nervous system complications (CNSCs) after cord blood (CB) than after bone marrow or peripheral blood transplantation (Kageyama K, et al. ASH 2016). Infectious complications such as human herpes virus type 6 (HHV-6) associated limbic encephalitis and/or myelitis have been the major cause of CNSCs. In this study, we now focused on non-infectious myelopathy and peripheral neuropathy (NIMPN) for which the main diseased focus located outside of cerebrum or cerebellum, since there has been little information available about them. The aim of the study is to clarify the incidence and the outcome of NIMPN after CBT. METHODS: We retrospectively studied medical records of 459 patients who underwent CBT as the first transplantation at Toranomon Hospital between July 2012 and March 2018. NIMPNs were diagnosed when the patients developed myelopathy or peripheral neuropathy without detection of pathogens tested in cerebrospinal fluid (CSF) or without radiological findings indicating hemorrhage, ischemia, or focal lesions suggestive of infections. We excluded the patients whose ECOG performance status scale was 3 or 4, and who had neurological symptoms before transplantation. Institutional review board of Toranomon Hospital approved the study (research number #1205-H) RESULTS: NIMPNs developed in 8 patients within 2 years after transplantation (2 myelopathies and 6 peripheral neuropathies [PN]). Their characteristics are as follows: the median age, 53 years (range, 37 - 62); 5 males and 3 females; AML-NOS (n = 5), AML with MRC (n = 1), therapy-related MDS or AML (n = 2). All except one were not in remission before transplantation. The combination of fludarabine, busulfan, and melphalan with or without high-dose cytarabine was used as conditioning regimen. Tacrolimus (Tac) alone (n = 2), Tac and mycophenolate mofetil (n = 5), and Tac and methotrexate (n = 1) were used as GVHD prophylaxis. The cumulative incidence of NIMPNs was 1.74% at 2 years after transplantation (95% confidence interval, 0.54 - 3.93). The median onset day of NIMPNs was 90 days after transplantation for all patients (range, 25 - 255); 40 days for myelopathy, and 100 days for PN. All had varying degree of hypesthesia or paresis and were unable to walk by themselves at diagnosis. All developed neurological symptoms after engraftment. Grade 2 - 3 of acute GVHD preceded NIMPNs in all patients. At diagnosis, the following pathogens were confirmed to be negative by PCR in CSF; HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, BKV, toxoplasma. CSF cell count and protein level did not increase in all of them. Myelin basic protein level in CSF was elevated in 3 out of 6 patients (519 ng/L and 1358 ng/L for myelopathies, 1321 ng/L for PN), which suggested demyelinating changes. Oligoclonal bands were not detected. Spinal MRI study performed in 4 patients showed no abnormality. In line with previous reports, axonal degeneration was confirmed by nerve biopsy in 2 patients with PN. After the diagnosis of NIMPNs, all patients were treated with high dose intravenous immunoglobulin (IVIG) (400 mg/kg for 5 days). The median interval from diagnosis to treatment was 28 days (range, 5 - 71). IVIG was administered monthly for the median of 2 courses (range, 2 - 5). In 2 patients, rituximab or steroid pulse therapy was added on IVIG, respectively. After these treatments, symptoms improved in 6 out of 8 patients and they finally were able to walk by themselves (1/2 of myelopathy and 5/6 of PN). The remaining one died of severe liver acute GVHD and another one is hospitalized until now without recovery. The median follow-up days of survivors was 498 days (range, 74 - 2190). Seven out of 8 patients are currently alive. CONCLUSION: NIMPNs were observed after CBT with low incidence. Although all patients presented severe neurological symptoms at diagnosis, IVIG and immunosuppressive therapy had a therapeutic benefit, and their prognosis with respect to neurological symptoms and survival was not dismal. Disclosures Yamamoto: Bristol-Myers Squibb: Honoraria.

scholarly journals Randomised controlled trial of conditioning regimen for cord blood transplantation for adult myeloid malignancies comparing high-dose cytarabine/cyclophosphamide/total body irradiation with versus without G-CSF priming: G-CONCORD study protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e040467
Author(s):  
Seitaro Terakura ◽  
Takaaki Konuma ◽  
Masatsugu Tanaka ◽  
Yukiyasu Ozawa ◽  
Makoto Onizuka ◽  
...  
Keyword(s):  
Cord Blood ◽  
Study Protocol ◽  
Total Body Irradiation ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
High Dose ◽  
Blood Transplantation ◽  
Total Body ◽  
Randomised Controlled

IntroductionA better long-term quality of life after umbilical cord blood transplantation (CBT) is observed compared with transplants from other alternative donors, whereas graft failure and relapses after CBT are still major issues. To minimise graft failure and relapse after CBT, intensification of conditioning by the addition of high-dose cytosine arabinoside (CA) and concomitant continuous use of granulocyte-colony stimulating factor (G-CSF) are reported to convey a significantly better survival after CBT in some retrospective studies. To confirm the effect of G-CSF plus CA combination, in addition to the standard conditioning regimen, cyclophosphamide (CY)/total body irradiation (TBI), we design a randomised controlled study comparing CA/CY/TBI with versus without G-CSF priming (G-CSF combined conditioned cord blood transplantation [G-CONCORD] study).Methods and analysisThis is a multicentre, open-label, randomised phase III study that aimed to compare G-CSF+CA/CY/TBI as a conditioning regimen for CBT with CA/CY/TBI. Patients with acute myeloid leukaemia or myelodysplastic syndrome, aged 16–55 years, are eligible. The target sample size is 160 and the registration period is 4 years. The primary endpoint is the 2-year disease-free survival rate after CBT. The secondary endpoints are overall survival, relapse, non-relapse mortality, acute and chronic graft-versus-host disease, engraftment rate, time to neutrophil recovery, short-term adverse events, incidence of infections and causes of death.This study employs a single one-to-one web-based randomisation between the with-G-CSF versus without-G-CSF groups after patient registration. Combination of high-dose CA and CY/TBI in both groups is used for conditioning.Ethics and disseminationThe study protocol was approved by the central review board, Nagoya University Certified Review Board, after the enforcement of the Clinical Trials Act in Japan. The manuscripts presenting data from this study will be submitted for publication in quality peer-reviewed medical journals. Study findings will be disseminated via presentations at national/international conferences and peer-reviewed journals.Trial registration numbersUMIN000029947 and jRCTs041180059.

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.

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.

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.

Comparison of Single Versus Multiple Unit Umbilical Cord Blood Transplantation for Adult Hematologic Malignancy Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3545-3545
Author(s):  
Ronald Sobecks ◽  
Edward A. Copelan ◽  
Matt Kalaycio ◽  
Medhat Askar ◽  
Lisa Rybicki ◽  
...  
Keyword(s):  
Cord Blood ◽  
Acute Gvhd ◽  
Hematologic Malignancy ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Multiple Unit ◽  
Total Body ◽  
Grade 3 ◽  
Related Mortality

Abstract Abstract 3545 Umbilical cord blood transplantation (UCBT) is an alternative donor transplant approach for adult hematologic malignancy patients. Although UCBT was initially performed using single cord blood units (SCBU), a major limitation of this approach has been the low infused total nucleated cell (TNC) and CD34+ cell doses at the time of transplant. This accounts for delayed hematopoietic recovery post-transplant that increases the risk for infections and transplant-related mortality (TRM). Multiple unit (MU) UCBT has become an acceptable approach to increase the cell doses available for transplantation. We retrospectively compared outcomes for 38 consecutively treated adult hematologic malignancy patients who underwent SCBU (n=6) or MU (n=32) UCBT at our institution from October 1999 through April 2010. The median age was 49 years (range, 18–71) and 20 (53%) were men. Diagnoses included: 21 AML, 5 CML, 3 MDS, 5 ALL, 2 CLL, 1 NHL and 1 myelofibrosis. The majority of patients received myeloablative conditioning (n=32) most commonly with total body irradiation, etoposide and ATG (Sobecks et al, Br J Haematol 2010, in press) while those treated with reduced-intensity conditioning received fludarabine 40 mg/m2/day × 5 (days -6 through -2), cyclophosphamide 50 mg/kg (day -6), ATG 30 mg/kg/day × 5 (days -3 through +1) and total body irradiation 200 cGy (days -1 and 0; total dose 400 cGy). GVHD prophylaxis included a calcineurin inhibitor for all patients and most MU patients received mycophenolate mofetil. Among the SCBU group there were three 4/6 and three 5/6 HLA matches with the patient. For the MU group when considering the best matched UCB unit with the patient there were seven 4/6, nineteen 5/6 and six 6/6 HLA matches while for the worst matched UCB unit there were one 3/6, eleven 4/6, sixteen 5/6 and four 6/6 HLA matches with the patient. The SCBU group included more women than the MU group (100% vs. 38%, p<0.001). When comparing both groups there were no differences regarding age at transplant, race, CIBMTR comorbidity index score, median number of prior chemotherapy regimens, myeloid vs. lymphoid diagnosis, myeloablative vs. reduced-intensity conditioning, use of ATG, median TNC and CD34+ cell doses infused, time for neutrophil and platelet engraftment, graft failure or length of transplant hospitalization. However, as compared to the MU group the SCBU group had more grade 3–4 acute GVHD (HR 11.4, 95% CI 2.07–62.6, p=0.005) and a trend for more grade 2–4 acute GVHD (HR 2.80, 95% CI 0.85–9.22, p=0.09). There were no differences between the groups regarding the number of HLA disparities with the recipient when considering the worst matched, best matched or engrafting UCB unit. There also was no difference between the groups with regards to chronic GVHD. CMV infection developed in 2 (33%) SCBU patients and in 8 (25%) MU patients while other infections occurred in 5 (83%) SCBU patients and 30 (94%) MU patients. There has been 1 (17%) relapse in the SCBU group (ALL patient) and 3 (9%) in the MU group (1 MDS, 1 AML and 1 CML). One (17%) SCBU and 14 (44%) MU patients remain alive at a median follow-up of 15 months (range, 3–92 months). Deaths in the SCBU group included 2 acute GVHD, 2 disease relapses and 1 hemorrhage while in the MU group there were 10 infections, 2 pulmonary toxicities, 1 acute GVHD, 1 relapse, 1 hemorrhage, 1 graft failure, 1 multi-organ failure and 1 secondary malignancy. The respective 100 day mortality was 50% vs. 42%; 1 and 2 year transplant-related mortality 50% vs. 46% and 50% vs. 57%; 1 and 2 year relapse-related mortality were both 33% vs. 3% for the SCBU and MU groups. The greater amount of grade 3–4 acute GVHD in the SCBU patients could not be attributed to HLA disparities, conditioning regimen intensity, use of ATG, infused TNC or CD34+ cell doses. Further follow-up with more patients is required to confirm this finding and to adequately assess for a survival benefit between the groups. Novel approaches to enhance immune reconstitution and prevent infection after UCBT are warranted. Disclosures: No relevant conflicts of interest to declare.

Cost-Effectiveness of Double-Unit Cord Blood Transplantation Versus Single-Unit Cord Blood Transplantation in Adult Patients with Acute Leukaemia in France- On Behalf of SFGM-TC, Eurocord, ALWP-EBMT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3130-3130
Author(s):  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Namik Taright ◽  
Federico Garnier ◽  
Catherine Faucher ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cord Blood ◽  
Median Time ◽  
Acute Leukaemia ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Neutrophil Recovery ◽  
Blood Transplantation ◽  
The Cost ◽  
Mean Cost

Abstract Abstract 3130 Unrelated donor cord blood transplantation (UCBT) using a single (s) or double (d) CB unit has become a widely accepted treatment for hematologic diseases in the absence of an HLA identical stem cell donor. Retrospective studies have reported a reduced risk of relapse after dUCBT compared with sUCBT, however one limitation of using dUCBT is the cost of the 2 units, but comparison of the total cost of the 2 procedures has not yet been published. The aim of this study was to evaluate the outcome of adult patients transplanted for acute leukaemia in first remission and to access the cost-effectiveness of dUCBT compared to sUCBT). We analyzed clinical results and costs of 134 consecutive CBT performed in 31 transplant centers in France from 2001 to 2009. All hospital costs were estimated from donor search to 1 year after UCBT, according to the French public system. A Markov decision analysis model was used to calculate the QALY (quality-adjusted life years) and cost-effectiveness ratio (ICER). For cost-effectiveness analysis, reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) were studied separately. Forty patients were transplanted for ALL and 94 for AML in CR1. Median age was 42 years and median time from diagnosis to UCBT was 180 days. CMV serology for 49% of patients was negative. Sixty one patients received a sUCBT and 73 a dUCBT. Twenty eight percent of CB units were HLA identical to recipient or had 1 HLA disparity (antigen level for HLA-A and B allelic level for DRB1) and 72% had 2–3 HLA disparities. Median infused nucleated cell dose was 2.7×107/kg in sUCBT and 3.8×107/kg in dUCBT. Seventy nine patients received a RIC (97% TBI<4Gy based) and 55 a MAC (84% TBI ≥4Gy Based). The median follow-up was 31 months after sUCBT and 24 months after dUCBT. Neutrophil recovery was achieved in 115 patients (51 of 61 patients who received a sUCBT and 64 of 73 dUCBT), with a median time of 23 (6–53) days. No statistical difference was observed for neutrophil recovery after sUCBT or dUCBT. dUCBT was associated with a higher rate of acute GVHD grade II-IV: 56% versus 30% for sUCBT, p=0.003. At day +100, 53% of patients experienced CMV reactivation (37% after sUCBT and 71% after dUCBT, p=0.01), 45% had viral infection other than CMV and 49% had bacterial infection. Fifteen patients (11%) received a second transplant, 6 for graft failure (4 in sUCBT group and 2 in dUCBT group) and 9 for relapse (6 in sUCBT group and 3 in dUCBT group). The median interval between first and second transplant was 327 days. The estimated survival at 2 years was 40±6% vs 58±6% after sUCBT and dUCBT, respectively (p=0.04). Leukaemia-free survival at 2 years was 30±6% in sUCBT vs 49±6% in dUCBT, (p=0.09). Cumulative incidence of relapse at 2 years was lower after dUCBT: 29±4% vs to 42±4% after sUCBT, (p=0.04). No statistically significant difference was observed in terms of non-relapse mortality and incidence of chronic GVHD. The mean cost for donor identification and UCB acquisition was 28.164 € for sUCBT and 48.929 € for dUCBT. The estimated costs within 1 year after RIC-sUCBT was 133.790 € and it was 211.735 € after MAC-sUCBT. The estimated cost was 180.549 € after RIC-dUCBT and 205.375 €, after MAC-dUCBT. Table 1 summarizes details of costs by type of graft and conditioning. In the MAC group, dUCBT was associated with lower cost (minus 13.554€) and better effectiveness (plus 0, 53 QALY). The cost per QALY obtained after RIC-dUCBT compared with sUCBT was 91.199 €. In conclusion, In France, dUCBT is associated with higher incidence of acute GVHD, lower relapse and better survival in adults transplanted for acute leukaemia. With a MAC, dUCBT is the best option, and the cost per QALY obtained for dUCBT when using RIC is acceptable.Table.Estimated costs from donor search to 1 year after transplantation for single UCBT, double UCBT and type of conditioning regimen (MAC or RIC)sUCBTdUCBTCB unit search28 164 €48 929 €MACInitial hospitalisationMean duration (d)6665Mean cost137.757 €131.773 €Outpatient visitsNumber of days911Mean cost7.788 €9.223 €Further hospitalisationsMean duration (d)5023Mean cost38.026 €15.449 €Total mean cost within 1 year211.735 €205.374 €RICInitial hospitalisationMean duration (d)2948Mean cost58.621 €96.335 €Outpatient visitsNumber of days2123Mean cost17.870 €19.366 €Further hospitalisationsMean duration (d)4021Mean cost29.135 €15.918 €Total mean cost within 1 year133.790 €180.549 € Disclosures: No relevant conflicts of interest to declare.

Infliximab Versus Rabbit Anti-Thymocyte Globulin As a Salvage Treatment For Steroid-Refractory Acute Graft-Versus-Host Disease After Reduced-Intensity Cord Blood Transplantation In Adults

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4592-4592
Author(s):  
Kazuya Ishiwata ◽  
Hisashi Yamamoto ◽  
Kousei Kageyama ◽  
Daisuke Kaji ◽  
Sachie Wada ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Survival Rates ◽  
Salvage Treatment ◽  
Primary Therapy ◽  
Blood Transplantation ◽  
Reduced Intensity ◽  
Steroid Refractory

Introduction In reduced intensity cord blood transplantation (CBT) post transplant immune disorders, including early immune reactions (PIR) and acute GVHD, are potential complications following CBT in adult patients. Such reactions might increase the risk of organ dysfunction, leading to high rates of transplantation-related mortality, particularly in patients who do not respond to primary therapy, which usually consists of steroids. There is no consensus on the optimal salvage treatment of steroid-refractory acute GVHD. Patients and Methods We retrospectively reviewed 388 patients who underwent single-unit reduced intensity cord blood transplantation consecutively from June 2008 to October 2012 at Toranomon Hospital. Patients who were in poor performance status (ECOG PS >3), had active bacterial or fungal infections at the time of conditioning were excluded. The most frequently used conditioning regimens were fludarabine, alkylating agent (melphalan or busulfan) with total body irradination (TBI), tacrolimus plus mycophenolate mofetil for GVHD prophylaxis. Patients in whom acute GVHD developed received methylpredonisolone 1-2 mg/kg per day. If no partial or complete resolution of symptoms occurred, they were considered steroid-refractory and proceeded to salvage treatment with infliximab or ATG. The dose of infliximab was 5 mg/kg/day once weekly for at least 1 course. ATG was given at 1mg/kg/day once weekly for at least 1 course. An observational study compared response and survival rates in all consecutive patients receiving 1 of these 2 treatments. Results 52 patients among this group developed steroid refractory acute GVHD. Infliximab group (n=31) had a higher proportion of patients with grade III-IV GVHD (69% VS 59%, p=0.18). ATG group (n=21) had a higher proportion of patients with stage 3-4 liver GVHD (28% VS 5%, p<0.01). Infliximab or ATG therapy was initiated after a median of 12 days (range, 2 to 85 days; 10 days for infliximab group VS 22 days for ATG group; p<0.01) of steroids for primary therapy for GVHD. Both overall response (PR+CR) were significantly higher in the infliximab group compared with the ATG group (54.8% VS 33.3%, p=0.015 ). In multivariate analysis, time from first-line therapy (days<10) was an independent predictor of response (HR, 3.91; 95%CI, 1.10-13.8; p=0.034), infliximab therapy was not significant, (HR, 1.30; 95%CI, 0.42-3.99; p=0.18). Median follow-up of surviving patients from the date of initiation of salvage treatment was 21.6 months (range, 5.5-57.9 months).Overall, median survival was 2 months after salvage treatment (95% CI, 1-3), with 25% of patients surviving at 12 months (95%CI, 11-20). Patients who achieved a CR have better survival rates. GVHD was the main cause of death (50%). When comparing survival according to salvage treatment, better OS with infliximab (33.9% VS 22.8, p=0.08) in univariate analysis was not confirmed in multivariate analysis. In multivariate analysis, grade IV GVHD at steroid refractory GVHD onset (HR,7.1; 95% CI, 1.29-38.7; P=0.021), and gut involvement with bleeding (HR, 7.65; 95% CI, 1.35-43.2; P=0.024) were significantly associated with worse survival. Conclusion We conclude that infliximab has more activity than ATG in the treatment of severe steroid-refractory GVHD, and earlier initiation of salvage therapy may give better response. But outcomes remain poor. New methods to prevent and treat GVHD are needed. Disclosures: No relevant conflicts of interest to declare.

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