Acute pancreatitis in marrow transplant patients: prevalence at autopsy and risk factor analysis

Summary:This retrospective study comprehensively examined hepatic and gastrointestinal complications post-bone marrow transplant (BMT) in a heterogeneous group of 132 pediatric patients that underwent 142 transplants. Hyperbilirubinemia occurred in 28% of this population with clinically evident jaundice in 16%. Acute graft-versus-host disease (GVHD) occurred in 46% of the population, with liver involvement in 39% and intestinal involvement in 60% of those with acute GVHD. Veno-occlusive disease (VOD) occurred in 18% of the population. A greater increase in hepatic transaminases was noted in GVHD and VOD than nonspecific liver injury. Serum bilirubin may help to differentiate between VOD and hepatic GVHD. Biliary sludging occurred in 20% of patients and was associated with increased morbidity. Common post transplant gastrointestinal complications included mucositis in 90%, vomiting in 85% and abdominal pain in 71%. TPN support post transplant was required in 91%. Diarrhea occurred in 67% with the most common identified etiologies reported as GVHD (27%), viral (6%), Clostridium difficile (8%) infections and unknown (28%). Typhilitis developed in 3.5%. Melena or hematochezia occurred in 11 patients (8%). However, gastrointestinal bleeding was disproportionately represented in intensive care unit admissions (5/27) and 100 day mortality (5/21). Gastrointestinal and hepatic complications represent a major cause of morbidity and mortality in pediatric BMT recipients.

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

GI complications in pediatric patients post-BMT

Barker

Anderson

Sauvé

et al. 2005

“…The association of acute pancreatitis with severe gastrointestinal or liver aGVHD has been reported. 37,38 Marrow transplant recipients may be predisposed to developing pancreatitis because of biliary sludge, use of irradiation or cytotoxic drugs in the conditioning regimen, prolonged medication with corticosteroids and CSA, and viral infections. 39,40 Our data do not show a relation of pancreatitis to these factors, although in three patients adenovirus was detected in stool and/or gastric secretion only during the course of aGVHD.…”

Section: Discussionmentioning

confidence: 99%

Higher CD3+ and CD34+ cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia

Gaziev

Isgrò

Marziali

et al. 2011

We evaluated the incidence of GVHD, risk factors and the impact of graft composition on acute GVHD (aGVHD) in 92 children who underwent BMT for thalassemia following busulfan/cyclophosphamide (BUCY)-based conditioning regimens and GVHD prophylaxis with CSA/short-MTX and methylprednisolone. The incidence of grade 2-4 and 3-4 aGVHD was 35% (95% confidence interval (CI) 25-44) and 9% (95% CI 4-16), respectively. We found that CD3 þ and CD34 þ cell doses above the median were associated with high incidence of grade 2-4 aGVHD (49 vs 20%, P ¼ 0.005 and 46 vs 23%, P ¼ 0.021, respectively). In multivariate analysis, high CD3 þ (hazard ratio (HR) 4.6; 95% CI 1.4-14.7; P ¼ 0.010) and CD34 þ (HR 4.3; 95% CI 1.4-12.7; P ¼ 0.011) cell doses were associated with grade 2-4 aGVHD. We further examined the effect of CD3 þ and CD34 þ cell doses on aGVHD using quartile cutoff points and found a minimum threshold for CD3 þ (38 Â 10 6 /kg) and CD34 þ (4 Â 10 6 /kg) cells above which the incidence of grade 2-4 aGVHD is significantly increased. This study shows for the first time a positive correlation between the number of CD3 þ and CD34 þ cells and aGVHD in children receiving sibling BMT, and indicates that using tailored and more intensive post transplant immunosuppression may permit to better control aGVHD.

“…5 In an autopsy series of allo-SCT patients from Seattle, signs of pancreatitis were found in 28% of allo-SCT recipients, although a premortem clinical diagnosis was made in only 10% of those patients. 6 Two cases of pancreatitis apparently related to tacrolimus have been reported after liver transplantation. 7,8 However, to the authors' knowledge, tacrolimus-associated pancreatitis has not been reported yet in allo-SCT recipients.…”

Section: Discussionmentioning

confidence: 99%

“…6 Although pancreatitis seems much more common after intravenous pentamidine, a few cases of aerosolized pentamidine-related pancreatitis have been reported. 9,10 Intravenous pentamidine-associated pancreatitis appears to develop after an accumulated dose of more than 1 g, whereas this patient had received a cumulative dose of 300 mg of inhaled drug at the time of symptom onset.…”

Section: Discussionmentioning

confidence: 99%

Acute pancreatitis during immunosuppression with tacrolimus following an allogeneic umbilical cord blood transplantation

Nieto¹,

Russ²,

Everson

et al. 2000

Summary:Tacrolimus is increasingly used for graft-versus-host disease (GVHD) prophylaxis and therapy in the allogeneic stem cell transplant (allo-SCT) setting. Pancreatitis, previously described as a side-effect of cyclosporine, has not been reported in allo-SCT recipients receiving tacrolimus. We present here a case of acute pancreatitis in a 28-year-old patient with chronic myelogenous leukemia (CML) who received an unrelated umbilical cord blood transplant (UCBT) and tacrolimus for GVHD prophylaxis. On day +31 post-transplant, she developed severe acute pancreatitis with multiorgan failure, from which she recovered completely. Tacrolimus was the probable cause of pancreatitis in this patient. Bone Marrow Transplantation (2000) 26, 109-111. Keywords: tacrolimus; FK506; pancreatitis; cord blood transplant Tacrolimus is a new immunosuppressive agent with an emerging role in allo-SCT. While its chemical structure is different from that of cyclosporine, both drugs share a similar mechanism of action, inhibiting signaling initiated by the T cell receptor that stimulates production of interleukin-2. 1 A recent randomized phase III trial comparing both agents for GVHD prophylaxis in the unrelated marrow transplant setting, showed that patients receiving tacrolimus had a significantly lower incidence of acute GVHD, and similar rates of chronic GVHD, relapse, and overall survival. 2 The toxic profile of tacrolimus, compared to that of cyclosporine, includes similar nephrotoxicity, hepatotoxicity, neurologic complications, hypomagnesemia, and immunosuppression-related infections. There appears to be less hypertension, hypertrichosis, and gingival hyperplasia, and more hyperkalemia and hyperglycemia with tacrolimus. 3,4 To our knowledge, pancreatitis has not been described in association to tacrolimus in the allo-SCT setting. Case reportThe patient was a 28-year-old female with chronic myelogenous leukemia (CML), diagnosed in 1996. She was treated with ␣-interferon plus hydroxyurea, and never achieved a complete cytogenetic remission. She had no HLAmatched sibling donors, nor an unrelated donor in any of the bone marrow registries. An unrelated 5/6 cord unit, HLA-mismatched for the DR locus, was identified at the University of Colorado Umbilical Cord Blood Bank. She consented to participate in a clinical trial of ex vivo expanded UCBT for adult patients.Conditioning therapy consisted of fractionated TBI at 12 Gy, melphalan at 140 mg/m 2 i.v., and antithymocyte globulin at 30 mg/kg × 3 days. On day 0, cord blood cells, a fraction of which (40%) were expanded ex vivo, were infused. Supportive care included standard antimicrobials, and GVHD prophylaxis with cyclosporine at a dose of 4 mg/kg/day, adjusted to a whole blood level of 350-450 ng/ml, and methylprednisolone at 0.2 mg/kg twice a day from day 0 to +4, 0.5 mg/kg twice a day from day +5 to +20, and in a tapering schedule thereafter. On day +16 posttransplant, tacrolimus was substituted for cyclosporine because of the patient's complaints of severe headache and visual...