scholarly journals Intensified Myeloablative Unrelated Cord Blood Transplantation for High-Risk or Advanced Hematological Malignancies: Experience at a Single-Institution in China

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1222-1222
Author(s):  
Zimin Sun ◽  
Huilan Liu ◽  
Baolin Tang ◽  
Xiaoyu Zhu ◽  
Wen Yao ◽  
...  
Keyword(s):  
Retrospective Study ◽  
High Risk ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Hematological Malignancies ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Neutrophil Engraftment

Abstract Introduction : Unrelated cord blood transplantation (CBT) is one of the most promising curative treatment modalities for hematological malignancies. But the data was limited in China. This retrospective study evaluated the clinical outcomes of intensified myeloablative unrelated CBT for high-risk or advanced hematological malignancies in our single center. Patients and Methods: From September 2006 to December 2013, Total of 187 high-risk or advanced hematologic malignancies underwent intensified myeloablative unrelated CBT. All CBT patients received a myeloablative conditioning regimen of TBI/Ara-C/CY [total body irradiation (TBI, total 12 Gy, 4 fractions) (d-7, d-6) arabinoside cytarabine (Ara-C) (2.0g/m2 every 12h for 2 days) (d-5, d-4) and cyclophosphamide (CY, 60 mg/kg daily for 2 days) (d-3, d-2)] (age≥14 years or primary induction failure or no remission after relapse), or Fludarabine/BU/CY2 [fludarabine (Flu, 30mg/m2 daily for 4 days) (d-8~ -5), busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)] (For lymphoid malignancies patients with age ＜14 years or prior radiotherapy which would presuppose a high risk of toxicity), or Ara-C/BU/CY2 [ Ara C (2.0g/m2 every 12h for 2 days) (d-9, d-8), (busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)](for myeloid malignancies patients with age < 14 years or prior radiotherapy which would presuppose a high risk of toxicity), and G-CSF was given with 5 ug/kg daily by subcutaneous injection one day prior to Ara-C with 3 days. For GVHD prophylaxis, all patients were given a combination of cyclosporine and short-course mycophenolate mofetil, and no patient received antithymocyte globulin (ATG). Results: Total of 181 patients (97.3%) achieved neutrophil engraftment and platelet engraftment, and the median number of days was 18 days (range 12~37 days) and 37.5days (range 15~112 days), respectively. Total nucleated-cell dose (≥5.2×107 / kg) and total CD34+ cell dose (≥3.8×105 / kg) were the favorable factors predicting for a higher probability of neutrophil engraftment (p =0.012, 0.025). The cumulative incidence of pre-engraftment syndrome (PES) and day-100 grade Ⅱ-Ⅳ acute GVHD was 75.4% (95% CI, 65.2-84.2%) and 28.34% (95% CI, 28.13~28.55%), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute GVHD 100 days after transplantation was 32.6% (95% CI, 42.3-22.8%)in the PES group and 15.2% (95% CI, 8.3-22.6%) in the non-PES group (р=0.016). Multivariate analysis showed that BU/CY2 based conditioning and without PES were significant risk factors for graft failure [RR=2.34 (95% CI, 1.32- 6.12), p =0.015; RR=2.89 (95% CI, 1.25- 6.82), p =0.009]. The median follow-up time was 27（7~89）months. Transplant-related mortality at 180 days and relapse at 3 years after CBT was 24.9% (24.7~25.2%) and 14.7% (14.6~14.9%). Probabilities of 3-year overall survival (OS) and disease-free survival (DFS) were 61.2% (95% CI, 51.3%- 72.3%) and 58.6% (95% CI, 49.5%- 67.9%), respectively. For pediatric patients, 3-year OS and DFS were 66.2% (95% CI, 56.4%- 75.8%) and 64.8% (95% CI, 54.6%- 74.2%); for adult patients, 3-year OS and DFS were 54.5% (95% CI, 45.8%- 63.7%) and 50.3% (95% CI, 41.5%- 60.1%), respectively. Conclusions: To the best of our knowledge, this is the largest clinical study of unrelated CBT reported in China. This retrospective study indicates that intensified myeloablative CBT procedures are associated with significant favorable outcomes in survival advantage in high-risk or advanced hematological malignancies. Disclosures No relevant conflicts of interest to declare.

Intensified Myeloablative Conditioning Regimen without Antithymocytic (ATG) Results in Superior Patient Outcome Compared to Myeloablative Conditioning Regimen for Single-Unit Umbilical Cord Blood Transplantation in Hematological Malignancies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5837-5837
Author(s):  
Zimin Sun ◽  
Huilan Liu ◽  
Yue Wu ◽  
Changcheng Zheng ◽  
Baolin Tang ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cumulative Incidence ◽  
Single Unit ◽  
Hematological Malignancies ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
Blood Transplantation ◽  
Group A ◽  
Neutrophil Engraftment

Abstract The superiority and safety of strengthening conditioning regimen for single- unit unrelated cord blood transplantation (sUCBT) in hematological malignancies remain controversial. We retrospectively analyzed the clinical data of 251 hematological malignancies undergoing sUCBT from Apr 2000 to Dec 2014 at Department of hematology in Anhui Provincial Hospital. Out of the 251 patients, 216 received the intensified myeloablative conditioning regimen (IMCR), and 35 received the myeloablative conditioning regimen (MCR). We evaluated the effect of IMCR without using Antithymocyte globulin (ATG) on patient outcomes. The cumulative incidence of myeloid and platelet engraftment of the IMCR group was significantly higher than that in the MCR group (96.98% vs. 82.81%, 85.89% vs. 51.79%, P=0.000 and 0.003, respectively). Corresponding incidences of transplantation-related mortality (TRM) by 180 days in the IMCR group and the MCR group were 19.50% vs. 41.67% (P=0.003), respectively. There were no differences in the incidence of grade II to IV acute GVHD (aGVDH), grade III to IV aGVHD and 2-year cumulative incidence of relapse. Up to Dec. 2015, with a median follow-up of 30 months, the estimated 3-year overall survival and disease- free survival in the IMCR group were both significantly higher than that of the MCR group (64.8% vs. 35.5%, 61.6% vs. 35.5%, P=0.000 and 0.001, respectively). This study is the first to show the superiority of intensified myeloablative regimen to conventional myeloablative regimen.A large-scale prospective study was needed. (A) (B) Figure 1 The cumulative incidence of neutrophil and platelet engraftment of the IMCR group and MCR group. (A)The cumulative incidence of neutrophil engraftment of the IMCR group was predominantly higher than that in the MCR group(96.98% vs. 82.81%, P=0.000). (B)The cumulative incidence of platelet engraftment of the IMCR group was also higher than that in the MCR group(85.89% vs. 51.79%, P=0.003). Figure 1. The cumulative incidence of neutrophil and platelet engraftment of the IMCR group and MCR group. (A)The cumulative incidence of neutrophil engraftment of the IMCR group was predominantly higher than that in the MCR group(96.98% vs. 82.81%, P=0.000). (B)The cumulative incidence of platelet engraftment of the IMCR group was also higher than that in the MCR group(85.89% vs. 51.79%, P=0.003). Figure 2 Comparison of the incidence of 3-year OS between the IMCR group and the MCR group.The incidence of 3-year OS of the IMCR group is predominantly higher than that of the MCR group(62.4% vs. 35.5%,P=0.001). Figure 2. Comparison of the incidence of 3-year OS between the IMCR group and the MCR group.The incidence of 3-year OS of the IMCR group is predominantly higher than that of the MCR group(62.4% vs. 35.5%,P=0.001). Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

Outcomes after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia. An Eurocord-Netcord Survey.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 304-304 ◽  
Author(s):  
Vanderson Rocha ◽  
Gerard Michel ◽  
Nabil Kabbara ◽  
William Arcese ◽  
Juan Ortega ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Advanced Phase ◽  
Unrelated Cord Blood

Abstract Unrelated cord blood transplantation (UCBT) is an alternative option to treat children with haematological diseases without an HLA-identical donor. We have analyzed a total of 323 children with ALL receiving an UCBT, from 1994 to 2004 in 99 transplant centres in 24 countries, mostly in Europe. Cumulative incidence with competing risk and KM estimates were used to calculate outcomes. Seventy six children were transplanted in CR1, 136 in CR2 and 111 in more advanced phase of the disease. Among those children poor cytogenetics were observed in 89% of children in 1CR, 33% in 2CR and 42% in advanced phase. Twenty percent of children transplanted in advanced phase had been previously autografted. The median age was 6.5 years at UCBT, median cell dose infused was 4.1x107/kg and the median follow time was 22 months (3–96). The cord blood was HLA identical (6/6) in 12% of the cases, 5/6 in 46%, 4/6 in 39% and 3/6 in 3%. All children received myeloablative conditioning regimen (TBI in 66%) and the majority (67%) received CsA+corticoids as GVHD prophylaxis. Cumulative incidence of neutrophil recovery at day 60, platelets recovery (&gt;20.000) at day 180, acute (grade II–IV) and chronic GVHD were 76±5%, 54±5%, 42±3%, 14±2%, respectively. Overall 2 year-LFS was 36±3%. In a multivariate analysis, only CR1 or CR2 were associated with better LFS (HR=1.8; p&lt;0.0001). Outcomes CR1 (n=76) CR2 (n=136) Advanced (n=111) TRM at day 100 22+/−5% 25+/−4% 34+/−5% Relapse at 2 years 34+/−8% 37+/−5% 48+/−7% LFS at 2 years 42+/−6% 41+/−4% 24+/−4% For those patients transplanted with poor cytogenetics, LFS at 2 years was 32±6% and it was 37% for CR1, 43% for CR2 and 0% for advanced phase of the disease. In conclusion, in these large series of high risk ALL patients, these results show that UCBT should be proposed as alternative source of allogeneic transplantation for children lacking an HLA identical donor, in earlier status of the disease.

Umbilical Cord Blood Transplantation after Reduced-Intensity Conditioning for Adults: The Report from Japan Cord Blood Bank Network.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2030-2030
Author(s):  
Naofumi Matsuno ◽  
Shuichi Taniguchi ◽  
Satoshi Takahashi ◽  
Shunro Kai ◽  
Yasuji Kozai ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Alkylating Agent ◽  
Cord Blood Transplantation ◽  
Cell Number ◽  
Blood Transplantation ◽  
Conditioning Regimens ◽  
Standard Risk ◽  
Neutrophil Engraftment

Abstract Umbilical cord blood transplantation (UCBT) is an alternative to bone marrow transplantation in adults when no sibling donor is available. Recently, UCBT after reduced-intensity conditioning (RI-UCBT) has been increasing in high risk adults not eligible for conventional conditioning. To evaluate the feasibility and effectiveness of RI-UCBT, we retrospectively analyzed the outcomes of 777 patients with hematologic diseases, who received RI-UCBT as the first allograft between 1997 and 2006 in Japan. Of 777 patients, 303 were women and 474 were men. Their median age was 56 years (range, 16–79 years). The patients’ diagnoses included 190 with acute myeloid leukemia, 66 with acute lymphoblastic leukemia, 22 with chronic myeloid leukemia, 172 with myelodysplastic syndrome, 193 with malignant lymphoma, 68 with adult T-cell leukemia/lymphoma, 44 with multiple myeloma, and 22 with aplastic anemia. Of 770 evaluable patients, 272 were defined as standard risk, whereas 498 were defined as high risk. Cord blood units were obtained from Japan Cord Blood Bank Network. The median total nucleated cell (TNC) number and median CD34+ cell number were 2.54 (range, 1.10–6.42) × 107/kg and 0.77 (range, 0.01–12.32) × 105/kg, respectively. Forty-two, 216, 512 and 4 patients received 6 of 6, 5 of 6, 4 of 6 and 3 of 6 serological HLA matched cord blood, respectively. The most frequently used conditioning regimens were fludarabine (Flu), alkylating agent (melphalan, busulfan or cyclophosphamide) with total body irradiation (TBI). The most frequently used prophylaxis regimens for graft-versus-host disease (GVHD) were calcineurin inhibitor (CI) alone in 431 patients and CI plus methotrexate in 206 patients. Cumulative incidence of neutophil engraftment was 67% at a median of 20 days after transplantation. Platelet recovery more than 20 × 109/L was observed in 47% at a median of 39 days. Among 542 evaluable patients, 206 developed acute GVHD of grade II or higher (cumulative incidence: 38%). The Kaplan-Meier estimates of overall survival (OS) and disease free survival at 2 years were 25% and 20%, respectively. Cumulative incidence of treatment-related mortality at day 100 was 36%. In univariate analyses, TNC number (&gt;2.5 × 107/kg) and CD34+ cell number (&gt;0.7 × 105/kg) were significantly associated with the neutrophil engraftment (P=0.0009 and P&lt;0.0001, respectively). Conditioning regimens consist of Flu, alkylating agent plus TBI were associated with favorable neutrophil engraftment and survival (P&lt;0.0001 and P=0.0013, respectively). Patients with younger age (&lt;56 years) or standard risk showed significantly longer OS (P=0.0013 and P&lt;0.0001, respectively). Multivariate analyses revealed that CD34+ cell number and conditioning regimens consist of Flu, alkylating agent plus TBI were significant independent factors for neutrophil engraftment (P&lt;0.0001 and P&lt;0.0001, respectively). Regarding survival, multivariate analyses revealed that age, disease risk and conditioning regimens were significant independent factors for OS (P=0.0013, P&lt;0.0001 and P=0.0002, respectively). In our retrospective analyses, a significant number of patients did not achieve engraftment or died from treatment-related complications. Further optimization of the treatment protocol is warranted to establish the safety of RI-UCBT.

Unrelated Cord Blood Transplantation (UCBT) in Adults with MDS or Secondary Acute Myeloblastic Leukemia (sAML): a Survey On Behalf of Eurocord and CLWP of EBMT.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1198-1198
Author(s):  
Marie Robin ◽  
Guillermo Sanz ◽  
Irina Ionescu ◽  
Bernard Rio ◽  
Anne Sirvent ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Median Time ◽  
Advanced Disease ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Neutrophil Recovery ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Unrelated Cord Blood

Abstract Abstract 1198 Poster Board I-220 Background: Unrelated cord blood transplantation is an alternative option to treat patients with high risk hematologic malignancies in the absence of an HLA identical donor. Results of UCBT in patients with MDS or secondary leukaemia (sAML) have been scarcely published. Method: We performed a survey to identify predictors of outcomes in a large cohort of 108 adults with MDS or sAML reported to Eurocord-Promise data bases (62 centres in 17 countries in Europe) and transplanted with an UCBT from 1998 to 2007. Sixty-seven patients were transplanted for sAML (secondary to MDS in 42 cases) and 41 for MDS. Worst status before UCBT for MDS was RA in 4, RAEB1 in 10, RAEB2 in 14, CMML or RAEBt in 9, unclassified in 4 patients. IPSS classification at transplantation was low, intermediate 1, intermediate 2, high or missing in 8, 12, 7, 6 and 8 patients, respectively. For patients with sAML, 48% were transplanted in CR1 at UCBT. Median age at UCBT was 43 years (from 18 to 72 years). Median time from diagnosis to UCBT was 10 months. Transplant characteristics: 77 patients received a single and 31 a double UCBT. UCB grafts had ≥ 2/6 HLA mismatched in 60 % of cases. Myeloablative conditioning regimen (MAC) was given to 57 patients whereas 51 patients received a reduced intensity conditioning regimen (RIC). GVHD prophylaxis consisted in CSA+MMF in 52, CSA+steroids in 43 and other combinations in 13 patients. Median number of collected nucleated cells was 3.4 for single and 4.6 × 107/kg for double UCBT. Median follow-up was 25 months. Results: cumulative incidence (CI) of neutrophil recovery at day 60 was 82±4% with a median time to achieve more than 500 ANC/mm3 of 23 days. Neutrophil recovery was independently associated with number of CD34+ cells/kg (> 1.1 × 105, Hazard Ratio (HR), 1.79; P= .02) and advanced disease status (intermediate 2 or high MDS and sAML not in CR; HR, 1.92; P= .007). CI of grade II-IV acute GVHD at day 100 and chronic GVHD at 2 years were 26±4% (II n=18, III n=6, IV n =6) and 42%±8, respectively. Two-year non-relapse mortality was significantly higher after MAC (62% vs. 34%, p=0.009). In counterpart, 2-year relapse rate was higher after RIC (14% vs 29%, p=0.02). Two-year DFS and OS were 30 and 34%, respectively. In univariate analysis, among patient-, disease- and transplant- factors studied only patients with high risk disease at maximal pre-transplant stage or transplanted > 18 months after diagnosis had significant poorer DFS (disease risk: 49% vs. 22%; time: 35% vs. 15%). However, in multivariate analysis, the only factor associated with decreased DFS was advanced disease (HR: 2.05; p= .01). Conclusion: These data indicate that UCBT is an acceptable alternative option to treat adults with high risk MDS or sAML without a HLA-matched related or unrelated bone marrow donor. Controlled disease at time of transplantation improves outcome. More investigations are needed to compare these results with outcomes after other stem cell sources from unrelated HSCT donor. Disclosures: No relevant conflicts of interest to declare.

Comparative Outcomes of Reduced-Intensity and Myeloablative Conditioning in Unrelated Cord Blood Transplantation for Adult Standard-Risk Hematological Diseases

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4498-4498
Author(s):  
Aya Nishida ◽  
Hikari Ota ◽  
Kazuya Ishiwata ◽  
Masanori Tsuji ◽  
Hisashi Yamamoto ◽  
...  
Keyword(s):  
Cord Blood ◽  
Relapse Rate ◽  
Cumulative Incidence ◽  
Cord Blood Transplantation ◽  
Myeloablative Conditioning ◽  
Hematological Diseases ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Standard Risk ◽  
Reduced Intensity

Abstract Abstract 4498 Background: Unrelated cord blood transplantation (uCBT) using reduced-intensity conditioning (RIC) is increasingly used for older and medically unfit patients. Data on the efficiency of hematopoietic stem cell transplantation (HCT) after RIC in younger and standard-risk patients are limited relative to myeloablative conditioning (MAC). Objective and method: To compare the outocomes of RIC to MAC in uCBT for adult patients with standard-risk hematological diseases, we retrospectively reviewed medical records of 57 standard risk hematological disease patients who underwent first uCBT at Toranomon Hospital from Jan. 2005 to December.2011. The definition of standard risk disease is severe aplastic anemia (SAA), myelodysplastic syndrome (MDS) in RA, RARS, and RCMD, acute myeloid or lymphoid leukemia (AML, ALL) in complete remission (CR) 1 or 2, chronic myeloid leukemia (CML) in chronic phase, malignant lymphoma (ML) and adult T-cell leukemia (ATL) in CR. RIC and MAC are defined according to previously reported criteria. Result: The median age of the studied patients was 55 years (range; 26–70). Twenty nine of patients received RIC and 28 MAC. Eleven patients of SAA, 7 MDS, 17 AML, 12 ALL, 5 CML, 2 ML, and 3 ATL were included in this study. Median follow-up days of survivors was 299 (11–2522). Cumulative incidence of neutrophil engraftment was 89.2% and the median days of engraftment is 20 days (11–51). Cumulative incidence of grade 2 to 4 acute graft versus host disease (aGVHD) was 42.9%. The 5-year disease-free and overall survival (DFS and OS) rates were 49.1% and 42.6%, respectively. The 5-years OS was comparable between MAC and RIC (RIC= 52.1% versus MAC= 44.2%; P=0.90). The 5-years OS of the elderly patients >54 years (n=27, 47%) were significantly lower than that in the younger patients (n=30, 53%) (35.1% versus 63.7%; P=0.042). The 5-years transplant-related mortality (TRM) was comparable between MAC and RIC (RIC= 35.0% versus MAC= 28.6%; P=0.56). The relapse rate was also comparable in two groups (RIC=11.9% versus MAC=33.6%; P=0.2) Conclusion: This study showed that uCBT with RIC for standard risk disease patients with median age of 55 years old had the similar results as MAC regimens in the 5-years OS, DFS, TRM and relapse rate. Disclosures: No relevant conflicts of interest to declare.

Reduced-Intensity Unrelated Cord-Blood Transplantation (RI-UCBT) for Patients with High-Risk Myeloid Malignancies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2891-2891 ◽  
Author(s):  
Koichiro Yuji ◽  
Shigesaburo Miyakoshi ◽  
Shinsuke Takagi ◽  
Daisuke Kato ◽  
Yuji Miura ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Myeloid Malignancies ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
Preparative Regimen ◽  
Unrelated Cord Blood ◽  
Reduced Intensity

Abstract &lt;Background&gt;Allogeneic stem cell transplantation (allo-SCT) is a curative treatment for advanced myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The therapeutic benefits are attributable to myeloablative radiochemotherapy and graft-versus-leukemia effect, whereas severe regimen-related toxicity (RRT) limits the efficacy of allo-HSCT to young patients without co-morbidities. Reduced-intensity stem-cell transplantation (RIST) using a non-myeloablative preparative regimen has been developed to decrease RRT, whilst preserving an adequate antitumor effect. RIST may be a curative treatment for heavily pretreated elderly patients with myeloid malignancies. Umbilical cord blood from unrelated donors has been used as an alternative stem cell source. We report the results of reduced-intensity unrelated cord-blood transplantation (RI-UCBT) in patients with advanced or high-risk myeloid malignancies. &lt;Patients and Methods&gt;Forty-eight patients (median age, 59 yr; range, 17–70) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2, melphalan 80 mg/m2, and 4 Gy of total body irradiation from 2002 to 2004. Twelve-seven patients were classified as AML not otherwise categorized, 16 as AML with multilineage dysplasia, 4 as RAEB and 1 as RA. The disease status at transplant was 2 CR1, 5 CR2 or CR3, 3 untreated and 38 refractory. The median infused total cell dose was 2.8 (range, 1.8–4.5) x 107/kg. HLA match was 6/6 in 1, 4/5 in 8, and 4/6 in 39 cases. GVHD prophylaxis was composed of cyclosporine (n=25) or tacrolimus alone (n=23). &lt;Results&gt; Fourty-three patients achieved primary neutrophil engraftment after a median of 20 days. Twelve patients developed grade II–IV acute GVHD and 7 developed chronic GVHD. Fifteen patients achieved CR. Eleven patients experienced relapse. Thirty-one patients died as a result of relapse (n=10), GVHD-associated complications (n=10), or infection (n=11). With a median follow-up of 489 days (range, 192–768), 17 of 48 patients are alive, resulting in a 2-year overall survival rate of 31% (95% CI, 16% to 45%). GVHD prophylaxis influenced outcomes (p&lt;0.05). &lt;Discussion&gt; These data suggest that RI-UCBT may be an effective option for patients with high-risk myeloid malignancies who lack an HLA-matched donor. RI-UCBT is associated with high TRM, providing a rationale for a larger clinical study, which should be modified to focus on enhancing any GVL effect, minimizing toxicities, and controlling infectious complications. Figure Figure Figure Figure

Post Transplant Autoimmune Hemolytic Anemia and Other Cytopenias Are Increased in Very Young Babies after Unrelated Donor Umbilical Cord Blood Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1054-1054 ◽  
Author(s):  
Kristin M. Page ◽  
Adam Mendizabal ◽  
Paul Szabolcs ◽  
Susan Wood ◽  
Vinod Prasad ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord Blood ◽  
Autoimmune Hemolytic Anemia ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Unrelated Donor ◽  
Umbilical Cord Blood Transplantation ◽  
Post Transplant ◽  
Blood Transplantation

Abstract Background: Unrelated donor umbilical cord blood transplantation (UCBT) is beneficial in the treatment of very young babies with early infantile, lysosomal storage diseases and hemoglobinopathies, diagnosed in utero or in the neonatal period. Methods: Over the past 9 years, we have treated 18 neonates (≤3 months of age at transplant) with Krabbe disease (n=11) metachromatic leukodystrophy (n=1), Tay Sachs disease (n=1), Hurler syndrome (n=2), Hunter syndrome (n=2), and Beta-Thalassemia Major (n=1) with UCBT after myeloablative conditioning therapy with Busulfan, Cyclophosphamide and ATG. All babies received cyclosporine + methylprednisolone (n=16) or cyclosporine + cellcept (n=2) for 9 months post transplant for prophylaxis against GvHD. Engraftment, acute and chronic GvHD, survival, treatment related mortality, and deaths were scored. Results: Eighteen babies were transplanted and 17 were evaluable for engraftment, GvHD, and survival. One baby died before engraftment of pulmonary hypertension day 15 post transplant. The cumulative incidence of overall survival was 94.4% (95% CI 83.9%–100.0%), 88.9 (95% CI 74.4%–100.0%) and 77.8% (95% CI 53.8%–100.0%) at 1, 2, and 5 years, respectively. In these infants receiving very high cell doses from their UCB graft (median total nucleated cell dose of 18.71x107/kg), neutrophil engraftment with an ANC >500/uL occurred at a median of 19 days with a cumulative incidence of engraftment of 94.1% (95%CI 77.9%–100.0%) by 42 days. Platelet engraftment (platelet count of 50K/uL untransfused) occurred in a median of 56 days with a cumulative incidence of engraftment of 94.1% (95%CI 77.8%–100.0%) at 6 months post transplant. Grade I-II acute GvHD occurred in 15/18 infants while one infant developed grade III acute GvHD of skin and gut. The cumulative incidence of grade II-III acute GvHD by day +100 was 29.4% (95%CI 6.9%–51.9%). Nine of seventeen evaluable patients developed cGvHD manifesting as autoimmune cytopenias with a cumulative incidence of 41.2% (95%CI 16.9%–65.5%) and 52.9% (95%CI 28.0–77.8%) at 1 and 2 years, respectively. In six patients, cGvHD presented as autoimmune cytopenia de novo. No graft factors were identified as being significant to development of cGvHD. All patients responded to treatment with methylprednisolone, azithroprine +/− rituximab. One patient required splenectomy. In contrast, the incidence of cGvHD in a group of otherwise similar older patients was 14.7%. Conclusion: We report an unexpected and high incidence of cGvHD manifesting primarily as autoimmune hemolytic anemia with other cytopenias, post UCBT in a population of very young babies. We hypothesize that post transplant immunosuppression interferes with the normal development of the immune system in the first year of life creating immune dysregulation and graft directed cell destruction. After lytic agents to stabilize disease, removal of chronic immunosuppressive therapy appears to facilitate recovery. Alternative strategies to prevent GvHD should be considered for this unique patient population.

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