scholarly journals Is Busulfan and Fludarabine an Optimal Myeloablative Hematopoietic Stem Cell Transplant (HSCT) Conditioning Regimen in Children with AML/MDS ?

2016 ◽  
Vol 22 (3) ◽  
pp. S350 ◽  
Author(s):  
Mohammed Ramzan ◽  
Muhammad ALI ◽  
Joerg Krueger ◽  
Sarah Alexander ◽  
Lee Dupuis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Hematopoietic Stem

scholarly journals Cytomegalovirus Management in Adult Hematopoietic Stem Cell Transplant Patients with Pre-Engraftment Viremia: A Single-Center, Retrospective, Descriptive Study

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S357-S357
Author(s):  
Isabella Martin ◽  
Robin Avery ◽  
Douglas Gladstone ◽  
Richard Ambinder ◽  
Noah Tucker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Bone Marrow Toxicity ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Cmv Disease

Abstract Background Scant data exist regarding cytomegalovirus (CMV) viremia in hematopoietic stem cell transplant (HSCT) recipients during the pre-engraftment period. The goal of this study was to describe management of CMV in neutropenic adult HSCT patients at our institution, and to assess the possible impact of different quantitative CMV PCR tests (QPCRs). Methods Post-HSCT monitoring at this center includes weekly CMV QPCR from plasma. Three different QPCR assays were used sequentially during the study period (1/2010–12/2015): two with lower limits of quantification (LLOQ) of 300 and 100 copies/mL through 4/2013, and after that the FDA-approved assay with LLOQ of 137 IU/mL. Medical records of first-time HSCT patients were reviewed. Pre-/peri-engraftment CMV was defined as detectable CMV DNA with [ANC] < 1000 cells/mm3. Information collected included demographics, donor/recipient CMV serostatus, conditioning regimen, CMV QPCR and ANC results, dates of CMV treatment, CMV disease within 100 days, and death within 6 months of HSCT. Data were analyzed with STATA v14. Results Of 1151 total HSCT, 76 patients had a positive CMV QPCR when ANC < 1000 cells/mm3. CMV was first detected a median of 12 days (0–48) post-transplant, and was above LLOQ at a median of 28 days (0–49). 71/76 (93%) were treated at a median of 33 days post-transplant (range 4–105 days), most with valganciclovir (40) or ganciclovir (30); 1 received foscarnet initially. 5 patients with low-level viremia were monitored without treatment. At initiation of therapy, median CMV level was 1471 (range 159–22,900) copies or IU/mL and ANC was 1202 (range 28–9680) cells/mm3. Median treatment duration was 34 days (range 9–392). Only 2 patients had possible tissue-invasive CMV disease. Conclusion Ganciclovir and valganciclovir were used to treat most pre- and peri-engraftment CMV viremia, despite potential bone marrow toxicity. The LLOQ of different CMV QPCR tests did not affect the viral threshold for starting treatment. The time between first CMV DNA detection (median day +12) and initiation of treatment (median day +33) suggests clinicians waited for CMV DNA and/or ANC to rise before treating. With this deferred-treatment approach, the proportion of patients with tissue-invasive disease remained low. Disclosures All authors: No reported disclosures.

scholarly journals Liver Injury after Autologous Hematopoietic Stem Cell Transplant: DILI and SOS

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2161-2161
Author(s):  
Alessandro de Moura Almeida ◽  
Helma Pinchemel Cotrim ◽  
Dayanne Costa Fonseca ◽  
Dora Marcia Alencar ◽  
Daniela Dourado Dutra ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Injury ◽  
Germ Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Germ Cell Tumors ◽  
Cell Transplant ◽  
Hematopoietic Stem

Abstract Introduction: Autologous Hematopoietic Stem Cell Transplant (AHCT) is an integral part of the treatment for many hematological and immunological diseases. However, the AHCT is associated with several complications, including liver diseases, such as sinusoidal obstruction syndrome (SOS), viral hepatitis, and sepsis-associated cholestasis. Drug-induced liver injury (DILI) is one of the most common and serious adverse drug side effects. This issue is particularly important in the context of high dose chemotherapy but it is still understudied. This study aims to determine the incidence of SOS and DILI among patients who underwent the autologous stem cell transplant. Methods: A retrospective cohort study was conducted among all patients who had undergone an autologous stem cell transplant at the hospital of Universidade Federal da Bahia (UFBA), Brazil, from July 2010 to July 2017. Daily weight and clinical and laboratory data ̶ aminotransferases, alkaline phosphatase (ALP), gamaGT (GGT), and total bilirubin (TB) levels ̶ were collected from beginning of the conditioning regimen to D+21 post-transplant. SOS diagnosis was based on modified Seattle Criteria (2 of 3 of the following items during the first 21 days post-transplant: TB ≥ 2mg/dl, hepatomegaly or upper right quadrant abdominal pain, and weight gain above 2% of pre-transplant weight). SOS severity was based on EBMT criteria. The International Serious Adverse Events Consortium 2011 criteria was used for DILI diagnosis, considering any of the following: (1) hepatocellular DILI: ALT ≥ 5 x upper limit normal (ULN); (2) cholestatic DILI: ALP ≥ 2 x ULN, especially in patients with elevated GGT, and without bone-disease-related ALP elevation; (3) mixed DILI: ALT ≥ 3 x ULN and total bilirubin (TB) ≥ 2 x ULN. All patients with SOS were excluded for the DILI diagnosis. All statistics were calculated using SPSS v 20.0 (SPSS Inc). Descriptive analysis and chi-square were applied, and the alpha error was 5%. The study protocol was approved by the institutional review board. Results: One hundred and seventy-five patients were included in the study. The mean age was 44.2 ± 15.4 years old, and 56.6% of patients (n= 99) were male. The main transplant indications were the following: multiple myeloma (55.4%, n= 97), lymphoma (36.0%, n= 63), acute myeloid leukemia (3.4%, n= 6), and germ cell tumor (3.4%, n= 6). Most patients presented aminotransferases (73.1%, n= 128) or ALP (44.0%, n= 77) elevations, but DILI incidence was 12% (n= 21). Hepatic, cholestatic, and mixed DILI were found in 3 (1.7%), 15 (8.6%), and 3 (1.7%) patients respectively. Five of six patients who developed hepatocellular or mixed DILI were exposed to etoposide (p=0.006). Cholestatic DILI occurred in 12 melphalan-based and 3 busulfan-based patients. The prophylactic use of ursodeoxycholic acid (UDCA) was associated with lower incidence of DILI (incidence among UDCA users: 1/43; incidence among non-users of UDCA: 20/132; p= 0,028). Mortality among DILI patients was 12% (n=2). SOS incidence was 6.9% (n= 12); 4 (33.3%) patients with mild, 4 (33.3%) with moderate, 2 (16.7%) with severe, and 2 (16.7%) with severe SOS. A higher incidence of SOS was found among recipients who was transplanted for germ cell tumors (p= 0.004); those previously submitted to abdominal irradiation (p= 0.068) and iron overload (p= 0.068); only one patient died from this syndrome. Almost all (83.3%; n=5) patients submitted to AHCT for germ cell tumors (using carboplatin + etoposide as conditioning regimen) developed liver injury (3 patients developed SOS and 2 developed DILI). Conclusion: Liver injury associated with the autologous hematopoietic stem cell transplant, represented mainly by DILI and SOS, had a high incidence (18.9%) among the subjects in the study and was associated with an elevated mortality rate. Drug induced liver injury has been underestimated and deserves further studies. Disclosures No relevant conflicts of interest to declare.

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