scholarly journals Correlation of nutrition-associated parameters with non-relapse mortality in allogeneic hematopoietic stem cell transplantation

2021 ◽  
Author(s):  
Judith Schaffrath ◽  
Tanja Diederichs ◽  
Susanne Unverzagt ◽  
Maxi Wass ◽  
Ulrike Gläser ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Nutritional Status ◽  
Stem Cell Transplantation ◽  
Serum Albumin ◽  
Cell Transplantation ◽  
Total Protein ◽  
Serum Total Protein ◽  
Hematopoietic Stem ◽  
Median Serum

AbstractOutcome of allogeneic stem cell transplantation (alloSCT) is hampered by substantial non-relapse mortality (NRM). Given its impact on organ function and immune response, the nutritional status has been suggested as relevant for NRM. We aimed to evaluate the association of NRM with nutritional status prior to alloSCT and in the post-SCT course. In a retrospective single-center study, we analyzed 128 alloSCTs. Besides standard characteristics, nutrition-associated parameters BMI, serum total protein, and serum albumin were recorded before conditioning and at various time points after alloSCT. Association with NRM was evaluated by univariate and multivariate survival analysis. The cohort comprised patients with a median BMI of 26 kg/m2 (16.7–46.9 kg/m2), median serum total protein of 59 g/l (41–77 g/l), and serum albumin of 36 g/l (22–46 g/l) before SCT. NRM at d+100 was 14.8% and at 1 year 26.6%. Prior to SCT, only serum albumin deficiency was associated with increased NRM (p = .010) in multivariate analysis. After SCT (d+30 and d+100), all nutrition-associated parameters decreased (p < .002), but no association of deteriorating nutritional status with NRM was found. In multivariate analysis, serum albumin (p = .03) and severe albumin deficiency (p = .02) correlated with NRM at d+30 and d+100, while BMI and serum total protein did not. In our study, albumin deficiency, particularly prior to alloSCT, shows a strong correlation with NRM. This finding may add to monitoring, risk evaluation, and counseling of patients and serve as a rational for interventions to improve the nutritional status in patients undergoing SCT.

Impact of ATG Dose on the Outcome of Patients Undergoing Reduced Intensity Conditioning Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies

2016 ◽  
Vol 136 (4) ◽  
pp. 193-200 ◽  
Author(s):  
Jérôme Cornillon ◽  
Marie Balsat ◽  
Aurélie Cabrespine ◽  
Emmanuelle Tavernier-Tardy ◽  
Eric Hermet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often proposed for patients with comorbidities. To enhance engraftment and limit graft-versus-host disease (GVHD), antithymoglobulin (ATG) is usually used. However, the dose needed remains unclear unlike myeloablative conditioning. In order to clarify this point, we conducted a retrospective study on patients who received a reduced intensity conditioning allo-HSCT based on a 2-day fludarabine and busulfan treatment with either 1 or 2 days of ATG treatment. One hundred and eight patients received 2.5 mg/kg (ATG2.5) and another 60 patients 5 mg/kg (ATG5). The median follow-up was 36 months. The median overall survival was 39 months and the median disease-free survival 45 months. In multivariate analysis, overall nonrelapse mortality (NRM) was independently influenced by the acute GVHD grade III-IV (p < 0.001) and ATG dose (30 vs. 21% for ATG5; p = 0.008). Despite heterogeneity of populations, using proportional-hazard assumptions, we have been able to observe in multivariate analysis a lower NRM in the ATG5 group. This leads to a statistically higher overall survival for the ATG5 group. In conclusion, 2 days of ATG decrease NRM independently without increasing the risk of relapse or infectious disease.

Allogeneic Hematopoietic Stem-Cell Transplantation In Early Phase Might Overcome the Adverse Prognosis of Acute Myeloid Leukemia with Translocation t(6;9)(p23;q34)/DEK-NP214(CAN) Rearrangement. A Retrospective Analysis From the Acute Leukemia Working Party of EBMT

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3501-3501 ◽  
Author(s):  
Jordi Esteve ◽  
Myriam Labopin ◽  
Gerard Socie ◽  
Per T. Ljungman ◽  
Johan Maertens ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Early Phase ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Abstract Abstract 3501 Acute myeloid leukemia (AML) with translocation t(6;9)(p23;q34)/DEK-NUP214(CAN) rearrangement (t(6;9) AML) is a rare but well-characterized entity, associated to a poor prognosis. In this regard, a possible benefit of allogeneic hematopoietic stem-cell transplantation (alloHSCT) has been suggested, based on small series of patients. To investigate the potential role of alloHSCT for the management of t(6;9) AML we analyzed the outcome of patients with this AML subtype submitted to alloHSCT and reported to the ALWP, and compared it to other well-defined cytogenetic categories. Overall, we identified 74 patients (median age: 38, 18–65; 51% male) diagnosed with t(6;9) AML allografted since 1988 (median year of transplant: 2004). Most transplants were performed in complete response (CR1=56, 76%; CR2=8, 11%), whereas only a minority were performed in advanced phase (primary refractory, n=5; relapse, n=5). Donor was an HLA-identical sibling in 43 transplants (58%), and a matched unrelated donor in 24 (32%). Conditioning regimen consisted of a myeloablative regimen in most patients (n=61, 82%), and source of stem-cells was peripheral blood in 41 (55%) and bone marrow in 32 (43%). After a median follow-up of 51 months, 3-year leukemia-free survival (LFS), relapse incidence (RI), and non-relapse mortality (NRM) for patients allografted in CR1 was 51±7%, 19±6%, and 30±7%, respectively, whereas LFS for patients transplanted in other disease status was only 16±10% (p<0.0001). A multivariate analysis performed among patients who received alloHSCT in CR1 identified a short interval CR-alloHSCT (<90 days) as the only favorable outcome for LFS (3-yr LFS: 57±10% vs. 51±7%; hazard ratio, HR=0.36, 95% CI:0.15-0.89; p=0.03) and NRM (47±11% vs. 17±8%; HR:3.84, 1.18–12.5; p=0.03), whereas reduced-intensity conditioning was followed by a higher RI (3-yr RI: 32±20% vs.17±6%; HR:4.86, 1.06–22.36; p=0.04). Moreover, the outcome of t(6;9) AML patients submitted to alloHSCT in CR1 was compared to that of patients with normal cytogenetics AML (NC-AML, n=2767) and poor cytogenetics AML (PR-AML, n=714) also allografted in CR1 in a multivariate analysis which included main prognostic variables. Interestingly, LFS and RI after alloHSCT of t(6;9) AML patients was similar to that observed in patients with NC-AML (51±7% and 58±1% for LFS, 19±7% and 23±1% for RI, respectively). On the contrary, the outcome of PR-AML was significantly poorer to NC-AML, with a 3-yr LFS and RI of 38±2% (p<0.0001; HR=1.58, 1.39–1.82) and 41±2%, respectively (p<0.0001; HR=2.09, 1.76–2.49; figure). In conclusion, alloHSCT in early phase resulted in a favourable outcome in patients with AML associated to translocation t(6;9), comparable to that of patients with NC-AML, suggesting that this procedure might overcome the adverse prognosis associated to this entity. Disclosures: No relevant conflicts of interest to declare.

Use of First or Second Generation TKI for CML after Allogeneic Stem Cell Transplantation: a Study By the CMWP of the EBMT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4685-4685 ◽  
Author(s):  
Yves Chalandon ◽  
Simona Iacobelli ◽  
Jennifer Hoek ◽  
Linda Koster ◽  
Liisa Volin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Chronic Phase ◽  
Time Interval ◽  
Hematopoietic Stem ◽  
Persistent Disease ◽  
Factors Influencing

Abstract Background: Patients (pts) relapsing with CML after allogeneic hematopoietic stem cell transplantation (alloHSCT) may be treated with tyrosine kinase inhibitors (TKI) and/or donor lymphocyte infusions (DLI). As nowadays the majority of CML patients would have received at least imatinib prior to transplantation, we were interested in analizing a) the type of TKI used after alloHSCT, b) the indication for TKI treatment, c) the outcome of this treatment and d) the temporal relationship with DLI if given. Patients and methods: 435 pts received TKI after first allogeneic HSCT for CML for different reasons. Transplants had been performed in first chronic phase (CP1, n=194), accelerated phase (AP, n= 60) or for more advanced disease (blast crisis (BC)/> CP1, n=177) from HLA identical siblings (n=231) or unrelated donors (n=204) between 2000 and 2013. TKI given prior to transplant was imatinib (n=268), dasatinib (n=162), nilotinib (n=88), bosutinib (n=4) and ponatinib (n=7). Median age at transplant was 44 (18.5-68) years, 274 pts (63%) were male. TKI post alloHSCT were given between 2000 and 2015. 1st TKI given was either imatinib (n=223), dasatinib (n=131), nilotinib (n=67), bosutinib (n=2) or ponatinib (12). The indications for TKI therapy were the same as for transplantation (n=262), for relapse/progression/persistent disease (n=124), for prophylaxis/pre-emptive (n=32), planned (n=5), others (n=8) and missing (n=4). Results: Median follow-up from start of TKI was 55 (1-171) months. The median time interval from transplant to TKI was 6 (0.2-165) months. It was longer for TKI given for relapse/progression with 15 (1-89) months and shorter for TKI given for prophylaxis/pre-emptive with 1.6 (0.2-43) months. It was longer for imatinib with 11 (0.2-121) months vs 3.8 (0.2-165) months for other TKI. Imatinib as 1st TKI was mainly given for relapse/progression/persistent disease (48%) and the other TKI for the same reason as for transplantation (83%). 103/223 (46%) of pts with imatinib, 99/131 (76%) with dasatinib, 55/67 (82%) with nilotinib and 11/14 (79%) with bosutinib/ponatinib post-transplantation had been treated with imatinib prior to transplantation. In total, 196 (45%) patients received DLI after alloHSCT, of which 63/435 (14.5%) had DLI prior to TKI post-alloHSCT, 19/435 (4.4%) had DLI at the same time of TKI and 114/435 (26%) had DLI post-TKI. Best response after TKI was complete molecular remission in 17.7%, cytogenetic remission in 4.4%, hematological remission in 20.2% and no response/progression/relapse in 57.7% of pts. 50% of pts treated with imatinib had a response (molecular/cytogenetic/hematological) vs 34% with nilotinib, 33% with dasatinib and 33% with bosutinib/ponatinib, p=0.014. OS was 60% (55-65%) at 5 years. It was 66% (60-73%) with imatinib vs 51% (42-60%) with other TKI, p=0.0024. 5 years RFS was 47% (42-53%). It was 53% (46-60%) with imatinib vs 40% (32-48%) with other TKI, p=0.0102. 5 years RI was 25% (21-30%). It was 21% (16-27%) with imatinib vs 31% (24-38%) with other TKI, p=0.0454. 5 years NRM was 27% (23-32%). It was 26% (20-31%) with imatinib vs 29% (22-36%) with other TKI, p=0.365. In multivariate analysis for OS, imatinib vs other TKI post-transplant did not show anymore an effect, HR 1.19 (0.85-1.67), p=0.317. Factors influencing OS were time from diagnosis to transplant, HR 1.01 (1.00-1.01), p=0.009, AP vs CP1, HR 1.80 (1.11-2.91), p=0.017 and BC/>CP1 vs CP1, HR 2.3 (1.58-3.33), p<0.0001. In multivariate analysis for RFS as for OS, imatinib vs other TKI did not have an effect, HR 1.11 (0.83-1.48), p=0.496. Other factors having a tendency or influencing RFS were time from diagnosis to transplant, HR 1.00 (1.00-1.01), p=0.054, AP vs CP1, HR 1.52 (1.00-2.31), p=0.050 and BC/>CP1 vs CP1, HR 2.11 (1.55-2.88), p<0.001. Conclusion: These data suggest that TKI after alloHSCT induce a response in about 42% of pts regardless of the type of TKI used and that time from diagnosis to transplantation as well as the phase of disease at transplant remain the main factors influencing the outcome of CML patients relapsing after alloHSCT. Disclosures Kröger: Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding.

Prognostic Factors of CLL Patients Undergoing Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation in the Immunochemotherapy Era

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5865-5865
Author(s):  
Oscar B. Lahoud ◽  
Patrick Hilden ◽  
Molly A. Maloy ◽  
Parastoo B. Dahi ◽  
Hugo Castro-Malaspina ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative therapy for chronic lymphocytic leukemia (CLL). With this analysis we intended to identify prognostic factors in patients undergoing reduced-intensity conditioning (RIC) or non-myeloablative (NMA) HCT at our center in the immunochemotherapy era. Methods: This retrospective chart review included all CLL patients who underwent RIC or NMA conditioned HCT at Memorial Sloan Kettering Cancer Center (MSKCC) in the immunochemotherapy era between 09/2006 and 10/2014. We then analyzed whether pre-HCT factors including age, disease response status at the time of HCT, presence of Richter's transformation, 17p deletion or TP53 mutation, use of anti-thymocyte globulin (ATG), number of prior lines of treatment, and time from diagnosis to HCT, were associated with overall survival (OS), progression-free survival (PFS), non-progression mortality, and grade 2-4 acute graft versus host disease (aGVHD). Univariate factors were evaluated via log-rank or Gray's test as appropriate, while Cox regression models were used to explore the adjusted effect of multiple factors. Results: Thirty-five patients undergoing RIC or NMA HCT with a median age of 53 years (range 36.3-69.0) were analyzed. The patients had a median of 4 prior lines of therapy (range 1-10) and a median time from diagnosis to HCT of 65.8 months (range 7.5-159.0). With a median follow-up for survivors of 58.8 months (95% CI 17.0-NA), the 5-year PFS and OS were 32.4% (95% CI 17.4-48.4) and 49.4% (95% CI 31.2-65.2), respectively (Figure 1). Treatment-related mortality was 20.0% (95% CI 8.7-34.7) and 31.8% (95% CI 17.0-47.6) at 1 and 2 years, respectively. Chemosensitive disease, defined by complete or partial remission per contemporary International Workshop CLL (iwCLL) response criteria at the time of HCT, was associated with improved 3-year OS of 68.0% (95% CI 46.1-82.5) compared to patients with chemorefractory disease to last line of therapy (stable or progressive disease) with a 3-year OS of 15.0% (95% CI: 1.0-45.7, p = 0.002, Figure 2). Additionally, patients with ≤4 lines of therapy prior to HCT experienced superior 5-year OS of 61.2% (95% CI 37.5-78.2) contrasted to 20.0% (95% CI: 3.1-47.5) in patients with >4 prior lines of therapy (p = 0.008, Figure 3). This difference approached statistical significance in multivariate analysis (HR 2.43, 95% CI 0.91-6.50; p = 0.076) adjusted for chemosensitivity. Furthermore, when adjusted for the number of prior lines of therapy, chemorefractory patients remained at greater risk of death in multivariate analysis (HR 3.29, 95% CI: 1.14-9.48, p = 0.027). Other factors including: age, history of transformed disease, the presence of 17p or TP53 deletion/mutation, time from diagnosis to HCT, or use of ATG with NMA/RIC did not impact PFS or OS. Conclusion: This is the first study to report independent prognostic impact of the number of lines of therapy prior to NMA/RIC HCT on OS for CLL patients in the post-immunochemotherapy era. We confer findings from other groups including: the prognostic significance of chemosensitivity at the time of HCT as well as HCT overcoming poor-risk cytogenetics associated with 17p chromosomal aberrations. Our data is limited by lack of patients previously exposed to recently FDA approved novel kinase or BCL2 inhibitors. Nevertheless, given our reported data, HCT should still be considered as the only therapy with curative potential for poor-risk patients earlier in their disease course, while chemosensitivity is maintained and prior to the accumulation of multiple lines of therapies. Disclosures Perales: Incyte Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Risk Factors and the Therapeutic Efficacy for Thrombotic Microangiopathy in Patients after Allogeneic Hematopoietic Stem Cell Transplantation - Results of the Multicenter Retrospective Cohort Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4554-4554
Author(s):  
Hiroharu Imoto ◽  
Hiroyuki Matsui ◽  
Yasuyuki Arai ◽  
Tadakazu Kondo ◽  
Yasunori Ueda ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Cohort Study ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Therapeutic Interventions ◽  
Post Transplantation ◽  
Hematopoietic Stem

[Introduction] Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, given its relatively low incidence, no large cohort-based study has determined TA-TMA risk factors and its impact on overall survival (OS) or the most effective therapeutic interventions. Recombinant human soluble thrombomodulin (rTM) is a promising therapeutic option; with dual antithrombosis and anti-inflammation activities, a single-center small cohort study in Japan reported rTM to be effective against TA-TMA. This study aimed to clarify risk factors for TA-TMA development and the efficacy of various TA-TMA therapies in a multicenter large cohort. [Methods] This retrospective cohort study conducted by the Kyoto Stem Cell Transplantation Group enrolled adult patients (age ≥ 16 years) with hematological diseases who underwent allogenic HSCT after 2000. Cumulative TA-TMA incidence was calculated using Gray's test; death from any cause was a competing risk. We evaluated OS in patients with or without TA-TMA using the Simon-Makuch method and compared it using the Cox proportional hazard model with TA-TMA development as a time-dependent covariate. Correlations were analyzed between each pre- or post-transplant factor and TA-TMA development using Gray's test. Factors significant in the univariate analysis were subjected to the multivariate analysis using the Fine-Gray proportional hazards model. We evaluated the effect of each therapeutics on response using a logistic regression model. [Results] We enrolled 2,430 patients [median age at HSCT, 50 (range: 16-74) years] from 14 institutes. Overall, 1,234 patients were transplanted for acute myeloid leukemia or myelodysplastic syndrome, followed by acute lymphoblastic leukemia (n = 381) and non-Hodgkin lymphoma (n = 351). Overall, 1,219 patients (50.2%) had advanced disease (non-remission status) at HSCT. The HCT-CI score was higher (≥3) in 213 patients (8.8%), and 360 (14.8%) were transplanted at poorer performance statuses (PS 2-4). In total, 471 patients (19.4%) received related bone marrow transplantation (BMT), 423 (17.4%) received related peripheral blood stem cell transplantation (PBSCT), 871 (35.8%) unrelated-BMT, and 665 (27.4%) unrelated cord blood transplantation. HLA was mismatched in 1,461 (60.1%) patients. After HSCT, TA-TMA was observed in 123 patients; the cumulative incidence of TA-TMA 12 months after HSCT was 5.0%; TA-TMA occurred at a median of 36 days (range: 3-482) (Figure 1). TA-TMA was correlated with a remarkably inferior OS [hazard ratio (HR), 4.93; 95% confidence interval (CI), 4.03-6.02; P < 0.001] when treating TA-TMA as a time-dependent covariate. In the multivariate analysis, poorer PS [HR, 1.64; 95% CI, 1.05-2.58; P = 0.03], higher HCT-CI [HR, 1.70, 95% CI, 1.02-2.83; P = 0.04], and HLA-mismatch [HR, 2.06; 95% CI, 1.34-3.17; P = 0.001] were significant pre-transplantation risk factors for TA-TMA. Post-transplantation factors (acute GVHD (Grade 3-4) [HR, 2.51; 95% CI, 1.64-3.85; P < 0.001] and veno-occlusive disease (VOD/SOS) [HR, 3.70; 95% CI, 2.05-6.70; P < 0.001]) were also significant risk factors for TA-TMA in the multivariate analysis. No infections (bacterial, viral, or fungal) were significantly related to TA-TMA incidence. Regarding therapeutic interventions, 36 (29.3%) patients received rTM-including treatment, 6 (5%) were treated with rTM alone, and 30 (24.4%) were treated with rTM and FFP (14; 11%), PE (5; 4%), or both FFP and PE (11; 9%). No significant differences in response rate [OR, 0.99; 95% CI, 0.39-2.52; P = 0.98] and OS [HR, 0.93; 95% CI, 0.58-1.49; P = 0.77] between the groups treated with or without rTM were identified. The results showed similar trends in other therapeutic interventions. [Conclusion] This study clarified the incidence of TA-TMA, its impact on clinical outcomes, risk factors including post-transplantation factors, and therapy efficacies. Patients with poor PS, high HCT-CI scores, and HLA-mismatched donors were high-risk patients; the development of severe acute GVHD and VOD/SOS also increased the risk of TA-TMA. rTM administration or other treatments did not improve patient outcomes. Therefore, strategies to avoid TA-TMA are essential. Intensification of the GVHD and VOD/SOS prophylaxis or treatment for these high-risk patients may reduce TA-TMA and improve HSCT outcomes. Figure 1 Disclosures Imada: Novartis Pharma K.K.: Honoraria; Takeda Pharmaceutical Co.,LTD.: Honoraria; Celgene K.K.: Honoraria; Bristol-Meyer Squibb K.K.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Ono Pharmaceutical Co., Ltd.: Honoraria; Kyowa Hakko Kirin Co., Ltd.: Honoraria; Astellas Pharma Inc.: Honoraria; Nippon Shinyaku Co.,Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria. Takaori-Kondo:Kyowa Kirin: Research Funding; Chugai: Research Funding; Takeda: Research Funding; Ono: Research Funding; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Janssen: Honoraria; Pfizer: Honoraria.

Hepatic Veno-Occlusive Disease in Children after Hematopoietic Stem Cell Transplantation: Incidence, Risk Factors, and Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4325-4325
Author(s):  
Soo Hyun Lee ◽  
Mi Mi Kwon ◽  
Young Joo Kwon ◽  
Hyeon Jin Park ◽  
Byung-Kiu Park ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Solid Tumors ◽  
Cell Transplantation ◽  
Medical Center ◽  
Hematopoietic Stem ◽  
Incidence Risk

Abstract Veno-occlusive disease (VOD) is one of the most frequent complications after hematopoietic stem cell transplantation (HSCT). We conducted this study to describe recent characteristics of incidence, risk factors, treatment and outcome of VOD in children undergoing autologous or allogeneic HSCT. Patients who underwent HSCT with hematological malignancies, solid tumors, or nonmalignant diseases at Asan Medical Center, National Cancer Center, Samsung Medical Center, and Seoul National University Children’s Hospital in Korea, from January 2005 to December 2007, were assessed with chart review. VOD was defined according to McDonald criteria and classified as severe on the basis of persistent symptoms after day 100 or death before day 100 with ongoing VOD. All other patients were considered to have mild or moderate VOD. Descriptive statistics and univariate and multivariate analyses of risk factors are presented. Four hundred sixty-seven HSCTs (217 autologous and 250 allogeneic HSCTs) were performed in 374 patients for the treatment of leukemia (n=177, 37.9%), neuroblastoma (n=103, 22.1%), brain tumors (n=69, 14.8%), nonmalignant diseases (n=62, 13.3%), and other solid tumors (n=56, 12.0%). For VOD prophylaxis, heparin was used in 116 transplants, heparin + prostaglandin E1 (PGE1) in 230 transplants, PGE1 ± ursodeoxycholic acid in 86 transplants, and defibrotide + heparin in 35 transplants. Among 467 transplant procedures, VOD developed in 72 transplants (15.4%) at median 10 days (range, 1–64) after HSCT. Five patients had recurrent VOD in their tandem transplantation. VOD was mild or moderate in 62 transplants and severe in 10 transplants. For treatment of VOD, PGE1, tissue-plasminogen activator, defibrotide, or antithrombin III were given alone or in combination of each other in 42 transplants. In remaining 30 VOD-positive transplants, patients were treated with supportive care only, such as restriction of sodium and fluid intake, diuretics and hematologic support. The median duration of VOD was 12 days (range, 3–80). Hepatomegaly was the most common sign of VOD (n=63). Ascites and inversion of portal flow were found in 17 (23.6%) and 8 (11.1%) of 72 VOD-positive transplants, respectively. VOD-related respiratory dysfunction and renal dysfunction were more frequent in transplants with severe VOD (7/10 and 7/10) compared to transplants with mild or moderate VOD (9/62 and 8/62) (P=0.001 and P&lt;0.0005). Multivariate analysis showed that total body irradiation (TBI) or busulfan containing regimen (P=0.003), VOD prophylaxis without PGE1 (P=0.005), pre-transplant serum ferritin (P=0.005), and number of previous HSCT (P=0.038) were independent risk factors for developing VOD. Underlying disease, stem cell source, donor type, age at transplantation, pre-transplant serum aspartate aminotransferase, and alanine aminotransferase did not influence the development of VOD. In addition, ascites (P=0.017) and number of previous HSCT (P=0.037) were significant risk factors for severe VOD by multivariate analysis. Deaths within 100 days after transplantation occurred in 13 of 72 VOD-positive transplants, the cause of death being VOD-related multi-organ failure in 5 cases. The risk of death within 100 days after HSCT was 2.8 times higher (95% CI: 1.718, 4.563) for VOD-positive transplants (P&lt;0.0005). TBI or busulfan-based conditioning regimen, VOD prophylaxis without PGE1, pre-transplant ferritin level, and repeated HSCT increased significantly the incidence of VOD in children after HSCT. The results can be used to identify high risk patients who are to undergo an HSCT. The encouraging result of our study is to justify the role of PGE1 in the prophylaxis of VOD, however prospective randomized trials are needed to confirm the superior efficacy of PGE1 in preventing VOD. Despite the combination of supportive cares and VOD therapy, significant numbers of patients are still suffering from VOD. Continued research for prevention and effective treatment of VOD will be necessary to improve the outcome of HSCT.

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