A Retrospective Study of Outcomes in Pediatric Hematology/Oncology Patients Receiving Continuous Venovenous Hemodialysis Y Avent 1, N Henderson 1, T Collie 1, RF Tamburro 2, L Elbahlawan 1, RR Morrison 1, S Rajasekaran 1 1 St. Jude Children’s Research Hospital, Memphis, TN 2 Pennsylvania State University College of Medicine, Hershey, Pennsylvania

Single Center Retrospective Review from January 2003-December bed ICU Total CRRT days 689 averaging 172 treatment days/year 41 patients received a total of 48 treatments Median age of this cohort was 12 years. Range (7.8 months -24 years) 23 males and 18 females –30 Hematopoietic Stem Cell Transplant (HSCT) patients (73%) Allogenic n=29 Autologous n=1 –11 non-HSCT patients (26%) Acute Lymphoblastic Leukemia n=5 Acute Myeloid Leukemia n=4 Ewing’s Sarcoma n=1 Glioblastoma Multiforme n=1 Study Design

CRRT Modality Modality –CVVHD Anti-coagulant –Citrate Dialysate –Normocarb HF TM Dialysate rates –(2000ml/hr x BSA)/1.73m 2 =ml/hr Blood Flow Rates –Average 2-4 ml/kg/min. Filters –Renaflo II – polysulfone membrane –PAN – polyacrylonitrile membrane Circuit Change –Every 3 days if patient’s clinical condition permits Machine –B Braun Diapact

Indications for CRRT 41 patients with 48 episodes of CRRT –Fluid overload n=12 –Renal Failure acute: n=29 transition from Intermittent Hemodialysis (IHD) to CRRT n=5 –Improving Fluid homeostasis in Congestive Heart Failure n=1 –Tumor Cell Lysis n=1

CRRT Variables HSCT patients 15.9±2.02 days therapy Non HSCT 9.6±2.9 days therapy 2 different filters used ( PAN and Renaflo) Of all variables statistically compared BUN > 75 at CVVHD initiation and C-Reactive Protein (CRP) at end of therapy were predictive of ICU death (p-value < 0.05). Hyperglycemia, high creatinine, oliguria and fluid balance not predictive of ICU mortality. A BUN > 29 mg/dL at day +7 was said to be predictive of mortality in HSCT patients in previous study. (Bacigalupo et al 1999)

CRRT Survivors HSCT patients (n=30) –ICU survival – HSCT pts 36% –Reasons for CVVHD D/C IHD Transition n=7 Improved renal function n=4 Support withdrawn n=2 Non-HSCT patients (n=11) –ICU survival – non-HSCT pts 42% –Reasons for CVVHD D/C IHD Transition n=2 Improved Renal Function n=3

ICU Non-Survivors HSCT ICU patients - 70% (21 of 30) –MSOD n=7 –Veno-occlusive disease of liver n=3 –Pulmonary failure n=3 –Sepsis n=2 –Cardiopulmonary failure n=2 –Relapse n=1 –Other n=3 –Median PRISM score at CRRT initiation n=17 Non-HSCT patients – 55% (6 of 11) –MSOD n=3 –Primary malignancy n=2 –Secondary malignancy n=1 –Median PRISM score at CRRT initiation n=21.5

Survivors Vs Non Survivors Non survivors had higher BUN at -24 * than survivors P<0.05. *

HSCT patients * Difference in CRP value reaches statistical significance* only at CVVHD end

ICU Issues HSCT patients - BUN > 75mg/dL and CRP are predictive of ICU mortality. Mechanical ventilation, use of pressors, hyperglycemia at CVVHD onset not predictive of ICU mortality. Oxygenation index and PF ratio in allogenic HSCT patients improved after 24 hours of CVVHD. –13.2±1.5 Vs 9.2±1.5 and 176.7±17.2 Vs 236±20.3 (Both indices P<0.05) Mean PRISM scores for CVVHD episodes among HSCT patients were 16.4±0.7 compared to non- HSCT 19.9±1.1 (not statistically significant)

6 month Survival HSCT patients - 3% (1of 30 patients) Only 3/30 HSCTs had recurrence of primary oncologic disease. Non HSCT patients – 36% (4 of 11 patients) survived to 6 months Overall 6 mo. Survival – 12% (5 of 41) Benoit et al reported 6 month survival in adult patients with hematologic malignancies at 14%.

Limitations of Study Small sample size makes it difficult to draw conclusions Findings may not be relevant to other centers Retrospective analysis No data regarding patients not referred to the ICU for CRRT Heterogeneity in primary oncologic disease and variation in oncologic therapy makes analysis difficult.

Conclusion Effective, safe renal replacement modality Resource intensive Non-HSCT patient ICU survival compares favorably with general ICU populations (Goldstein et al Pediatrics 107(6); June 2001) 6 month survival rates for HSCT patients is not encouraging

Ethical Considerations Poor 6 month survival outcomes for HSCT patients More selective in offering therapy if we can identify patients who are likely to survive to ICU discharge Managing expectations of families

Future Research Attempt to delineate factors which can translate short term success into 6 month survival for HSCT patients Parent/patient perceptions CVVHD vs. other modalities in HSCT patients Immune modulation with CVVHD PRISM scores for HSCT vs. Non HSCT patients