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Background: Grade III-IV toxicities in the 30 days post allogeneic hematopoietic cell transplantation (alloHCT) is correlated with higher transplant-related mortality (TRM) at 1 year in adults. Despite extensive literature in the field there remains a paucity of data on the incidence of grade III-IV toxicities in children and adolescents undergoing alloHCT.
Methods: Retrospective cohort study of 166 patients (0.1-22y) who underwent alloHCT from January 2000 and December 2013 for malignant and non-malignant disease. Patients were conditioned on 1 of 3 Busulfan (Bu)-based conditioning regimens: reduced intensity (RIC): Bu(6.4-8mg/kg)+ Fludarabine (Flu) [150mg/m2), reduced toxicity (RTC): Bu(12.8-16mg/kg)+ Flu (180mg/m2) and myeloablative (MAC): Bu(12.8-16mg/kg)+ cyclophosphamide (120-200mg/kg) or melphalan (135mg/m2). Toxicities were scored using the CTCAE grading system in the 30 days post-alloHCT.
Results: Median age at alloHCT was 8.5y (0.1-22y), malignant n=102, non-malignant n=64. Median number of grade III-IV toxicities in all groups was 3 (0-17). On univariate analysis, age ³12 (p=0.002) was the single risk factor associated with an increased incidence of grade III-IV toxicities in the 30 days post-transplant. Incidence of toxicities was not significantly different in malignant v. non-malignant groups, RIC v. RTC v. MAC regimens, donor, HLA, primary disease or hematopoietic co-morbidity index. 1yr TRM in patients with number of grade III-IV toxicities below median (<3) was 2.6% and 1yr TRM in those with above median ( ³3) toxicities was 15.6% (p=0.007). A total of 59 pediatric patients received MAC regimens, n=37 <12y and n=22 ³12. Of this cohort, 43% of patients <12y and 72.7% of patients ³12 had above median number of grade III-IV toxicities (p=0.034). 1 year TRM was 10.8% for <12y and 22.7% for ³12y (p=0.272). RIC and RTC regimens were not associated with more than median toxicities in patients ³12 yrs. Detailed information provided below.
Conclusion: Despite recent advances in alloHCT, toxicity and organ impairment remain a significant cause of morbidity and mortality during the first year following alloHCT. Our preliminary results suggest that higher incidence of grade III-IV toxicities in the 30 days post-alloHCT correlates with higher risk of TRM at 1yr. Age ³12y was significantly correlated with incidence of grade III-IV toxicities in the 30d post-transplant. Prospective studies to validate our finding and methods to decrease serious toxicities in adolescents are warranted.
Grade III-V toxicities
| Regimen | |||
MAC (n/%) 59/36
| RTC (n/%) 62/37
| RIC (n/%) 45/27
| Total (n/%) 166/100
| |
Hepatic
| 18/30
| 13/20.97
| 16/35
| 47/28
|
Renal
| 4/6.78
| 0/0
| 4/8.9
| 8/4.8
|
Gastrointestinal
| 20/34
| 28/45.1
| 7/15
| 55/33
|
Hemorrhagic cystitis
| 5/8.5
| 6/9.7
| 0/0
| 11/6.6
|
Cardiac
| 3/5
| 1/1.6
| 1/2.2
| 5/3
|
Lungs
| 9/15
| 6/9.68
| 1/2.2
| 16/9.6
|
Sepsis
| 9/15
| 4/6.45
| 2/4.4
| 15/9
|
VOD
| 12/20
| 3/4.8
| 2/4.4
| 17/10.2
|
Total # toxicities
| 79
| 61
| 35
| 175
|