Transplant-related toxicity and mortality: an AIEOP prospective study in 636 pediatric patients transplanted for acute leukemia

Abstract

Summary:Hematopoietic stem cell transplantation can cure highrisk acute leukemia (AL), but the occurrence of nonleukemic death is still high. The AIEOP conducted a prospective study in order to assess incidence and relationships of early toxicity and transplant-related mortality (TRM) in a pediatric population. Between 1990 and 1997 toxicities reported in eight organs (central nervous system, heart, lungs, liver, gut, kidneys, bladder, mucosa) were classified into three grades (mild, moderate, severe) and prospectively registered for 636 consecutive children who underwent autologous (216) or allogeneic (420) transplantation, either from an HLA compatible related (294), or alternative (126) donor in 13 AIEOP transplant centers. Overall, 47% of the patients are alive in CR (3-year EFS: 45.2%, s.e.: 2.1), 19% died in CR at a median of 60 days (90-day TRM: 14.3%, s.e.: 1.4), 34% relapsed. Toxicity of any organ, but mucosa and gut, was positively correlated with early death; moderate and severe toxicity to heart, lungs, liver and kidneys significantly increased early TRM, with estimated relative risks of 9.1, 5.5, 2.7 and 2.8, respectively, as compared to absent or mild toxicity. Patients with grade III-IV aGVHD experienced more than double (56% vs 19%) TRM than patients with grade 0-II aGVHD. A higher cumulative toxicity score, estimating the impact of toxicity on TRM, was significantly associated with transplantation from an alternative donor. Quantitative assessment allowed us to describe the

Autologous purified peripheral blood SCT in childhood low-risk relapsed ALL

“…Lower complication rates are expected for non-transplanted children, even though their treatment invariably includes cranial irradiation, which also increases the risk of brain tumors, and testicular irradiation or orchiectomy, in the event of testicular relapse. 50,51 For children undergoing allogeneic transplantation the same TBI-related side effects are expected as in the autologous setting, but amplified by immunological complications, that is GVHD and infections because of highly impaired immune reconstitution, which are expected to increase treatment-related mortality and long-term side effects. 50,54,[58][59][60][61] An allogeneic approach could be adopted for children who experience relapse after autologous transplant, such as the eight patients in this series, of whom four were rescued and are in long-term CR3.…”

“…49 Early complications consisted of mucositis, presenting at a median of 3 days (range 0-8) after graft infusion in 25 patients, and hemorrhagic cystitis at day þ 5 in one patient. 50 In terms of infections, no patient experienced early life-threatening infections. Fever occurred in 19 patients at a median of 4 days (range 1-19); this was of undetermined origin in 12 patients, associated with positive cultures in 2 and with positive chest CT scan in 5.…”

Outcome of allogeneic bone marrow transplantation for children with advanced acute myeloid leukemia

“…The incidence of RRT reported here is comparable to that seen in children with acute leukemia in general, particularly when considering the large number of alternate donor recipients in the cohort. 1,13,18,22 Previous studies have identified TBI, unrelated donor transplant, low marrow cell dose and transplant in relapse as risk factors for RRT. 22,38 Our analysis failed to reveal any specific risk factors statistically significantly associated with the probability of RRT, perhaps due in part to the limited number of events.…”

“…Compared to patients with AML in first CR, patients with more advanced disease are reported to have increased transplant-related morbidity and mortality. 14,22 The main objective of this study was to analyze the outcome of children who received an allogeneic BMT for AML beyond first CR, and to identify risk factors associated with failure of disease-free survival (DFS). We also report transplant-related morbidity including regimen-related toxicity (RRT) and graft-versus-host disease (GVHD).…”

Implications of different fluid overload definitions in pediatric stem cell transplant patients requiring continuous renal replacement therapy

“…These patients often require prolonged hospitalization and are exposed to multiple risk factors for AKI including episodes of hypotension, sepsis, veno-occlusive disease, radiation therapy and nephrotoxic agents used to treat co-morbid conditions [13,14]. The incidence of AKI in this population is estimated at 25-50% with 5-15% needing some form of renal replacement therapy [12][13][14][15][16]. For the patients that require CRRT, mortality rates approach 75% [9,12,[17][18][19].…”