Pre-Engraftment Syndrome After Myeloablative Umbilical Cord Blood Transplantation: Risk Factors and How To Stratify

Pre-engraftment syndrome (PES) is a group of symptoms occurred after hematopoietic stem cell transplantation especially unrelated cord blood transplantation(UCBT) before the engraftment, including unexplained fever higher than 38.3°CAunexplained erythematous skin rashAdiarrheaAhepatic dysfunction Anon-cardiogenic edemaApulmonary infiltrates and weight gain. Severe PES can be fatal, however there’s no criteria to define it. We retrospectively analyzed the incidence, risk factors, manifestations and clinical outcomes of PES in CBT recipients, who had been treated for hematologic malignancies. All patients received TBI(12GY)/Ara-c(8g/ m²)/CY(120mg/kg) without ATG or Flu(120mg/ m²)/Ara-c(8g/ m²)+BU(12.8mg/kg)+CY (120mg/kg) myeloablative conditioning.

From April 2010 to July 2011, 61 patients underwent UCBT at our transplantation center and 40 patients(65.6%) developed PES at a median of 7 d (range 5–13) post-transplant. We analyze 8 factors related to treatment-related mortality (TRM) within 180 days : occurrence timeAthe maximum temperatureAclinical symptomsAconcentration of CyclosporinAthe initial dose of MPAmethylprednisolone (MP) effective daysAdays till MP reduced and reoccurrence after symptoms under control. Univariate analysis identified early occurrence time( day +5 or +6 ) AMP effective days and clinical symptoms as significant risk factors for higher TRM. In a multivariate analysis, we found these three factors are independent and have no interactions. We retrospectively analyze all the patients who developed PES from April 2010 to December 2012.

There were 94 cases and we scored them based on these three factors. The patient got one score for each factor if he/she got a fever on day 5-6 after UCBT or had more than two clinical symptoms or not under control after 7 days of MP. We added the three scores together and divide the patients into four groups according to the total score(zero for Group 1Aone score for Group 2Atwo score for Group 3Athree for Group 4). The number of patients for Group 1-4 was 32A32A18 and 12. There is a significant difference for the TRM within 180 days between Group 4(58%) and Group 1(18.7%)AGroup 2(22.2%) (P<0.01). The TRM of Group 4 in one year is 66.7%, which is significantly higher than Group 1( 22.7%), Group 3(22.2%) (P<0.01), but shows less significant difference compared with TRM of group 2, which is 33%. The relapse rate of one year for each group from 1 to 4 was 9%A16.7%A5.5%A8.3%. The probability of one-year disease-free survival (DFS) was much higher in Group 1 (71.7%) and 3(72.2%) than Group 4(25%) (P<0.01). The difference was apparent as to the probability of one-year overall survival (OS) between Group 1 (74.8%) and 4(25%), the same is true whith Group 3 (71.3%) and 4(25%). The difference between Group 2(55.4%) and Group 4 was not clearly significant (P=0.06).

Recognizing and treating immediately severe PES will significantly reduce the TRM of UCBT. Our analyze confirmed that these three factors are crucial to define severe PES .We therefore put forward this ranking method to help to diagnosis and take effective treatment.

No relevant conflicts of interest to declare.