Antonio Pérez

Exercise during Hematopoietic Stem Cell Transplant Hospitalization in Children

PURPOSEnThe purpose of this controlled trial was to assess the effect of an approximately 3-wk intrahospital exercise intervention performed during inpatient hospitalization for pediatric allogeneic hematopoietic stem cell transplant (HSCT) on (i) immune cell recovery and (ii) body composition.nnnMETHODSnImmune (i.e., blood counts of leukocytes, monocytes, lymphocytes, and lymphocyte subpopulations) and anthropometric variables (i.e., body mass, body mass index, and estimated fat-free mass) were measured before and after (+15 and 30 d) HSCT. Seven children (5 boys and 2 girls; age (mean +/- SD) = 8 +/- 4 yr) with high-risk cancer performed an individualized training program (aerobic + resistance exercises) in their isolated hospital rooms. We also assessed a control group (n = 13; 9 boys and 4 girls; age = 7 +/- 3 yr) with similar medical conditions and following the same transplant protocol.nnnRESULTSnIn both groups, the dendritic cell count decreased from pre-HSCT to +15 d post-HSCT and thereafter (up to +30 d) remained stabile; however, the posttransplant decrease was more abrupt in the control group than that in the intervention group (-87% vs -63%, respectively, from pre-HSCT to +15 d). The rest of the immune cell parameters measured showed a similar response from pre-HSCT to post-HSCT in both groups. We found a significant effect of the interaction group x time for all anthropometric variables (weight, body mass index, body fat, and fat-free mass), indicating an increase over the hospitalization period only in the intervention group, for example, body mass increased from 32.9 +/- 18.7 kg pre-HSCT to 35.4 +/- 18.6 kg at +30 d in the intervention group versus a decrease from 30.2 +/- 16.6 to 29.3 +/- 6.3 kg in the control group.nnnCONCLUSIONnOur findings support the feasibility of exercise training interventions during hospitalization, including immunocompromised children.

Graft manipulation and reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation from mismatched unrelated and mismatched/haploidentical related donors in pediatric leukemia patients.

Transplant-related problems have been partially overcome by using reduced-intensity conditioning (RIC), graft engineering, and alternative donors. In all, 21 leukemia patients with no suitable donor received a hematopoietic stem cell transplantation from a mismatched/haploidentical related (n=16) or unrelated donor (n=5). Fludarabine-RIC and PBSC graft were used. Manipulation was done by CD34+ selection (n=9) or CD3/CD19 depletion (n=12). Results were compared with patients (n=26) conditioned with the same regimen and grafted with a CD34+-selected PBSC from identical related donors. Median time to neutrophil recovery was 12 days (range, 10-19u2009d). Platelet engraftment was faster with a CD3/CD19-depleted graft (median, 11u2009d; range, 9-21) than with a CD34+ graft (median, 14u2009d; range, 9-53; P=0.003). Full donor chimerism in bone marrow CD34+ cells was higher in CD3/CD19-depleted graft group compared with CD34+-selected group (P=0.02). CD3/CD19 depletion showed higher natural killer cell counts even after 1 year. Nonrelapse mortality (7% for matched CD34+-selected grafts and 11% for mismatched/haplo-CD3/CD19-depleted grafts), relapse probability (27% for related CD34+-selected patients and 33% for related CD3/CD19-depleted patients), and disease-free survival were similar for both the groups. In conclusion, using graft engineering procedures after RIC for hematopoietic stem cell transplantation offers a high probability of engraftment, fast immune recovery, and very low mortality even with mismatched donors.

Allogeneic hematopoietic transplantation using haploidentical donor vs. unrelated cord blood donor in pediatric patients: a single-center retrospective study.

We retrospectively analyzed outcomes in 67 children with acute leukemia who received hematopoietic stem cell transplantation from alternative allogeneic donors: 29 received a haploidentical family donor and 38, an unrelated cord blood donor. All transplantations were performed from 1996 through 2010 in our center. Neutrophil and platelet engraftment were significantly delayed after cord blood transplantation. The median times to neutrophil and platelet recovery were 13u2003d (7–34) and 11u2003d (5–70) after haploidentical transplant and 20u2003d (9–125) and 56u2003d (12–200) after cord blood (Pu2003<u20030.001). All supportive care measures included red blood cell, and platelet transfusions were significantly increased in cord blood transplantation group.Transplant‐related mortality rates was lower with haplo donors (25u2003±u20039%) than with cord blood donors (47u2003±u20039%) (Pu2003<u20030.05). Acute graft‐versus‐host disease (GVHD) more than grade II was also lower in haploidentical transplants (19u2003±u20037%) than in cord blood transplants (44u2003±u200310%) (Pu2003<u20030.03). Relapse and chronic GVHD incidence were not significantly different in the two groups. Leukemia‐free survival was higher after haploidentical transplants (44u2003±u200310%) than after cord blood transplants (33u2003±u20037%) (Pu2003<u20030.03). Main differences were observed in patients diagnosed with acute lymphoblastic leukemia: haplo, 41u2003±u200313%; cord blood, 26u2003±u20039% (Pu2003<u20030.03) and in advanced phase of disease: haplo, 37u2003±u200314%; cord blood, 21u2003±u20038% (Pu2003<u20030.05). In conclusion, haploidentical transplants are a good and promising alternative option for patients with childhood leukemia who lack an human leukocyte antigen‐matched donor (sibling or unrelated donor).

Engraftment syndrome after autologous peripheral blood progenitor cell transplantation in pediatric patients: a prospective evaluation of risk factors and outcome.

Summary:We prospectively analyzed the incidence, risk factors and outcome of engraftment syndrome (ES) in 112 patients undergoing autologous peripheral blood progenitor cell transplantation with different malignancies between January 1999 and December 2003. The median age was 8 years (range 1–18). There were 73 males. There were 37 hematological neoplasias and 75 solid tumors. Disease status at transplantation was early in 49, intermediate in 15 and 48 in advanced phase. The median CD34+ cells infused was 4.6 × 106/kg. With a median follow-up of 23 months (1–116 months), 38 patients developed ES. The cumulative incidence of ES was 34.5±4.5% and the event-free survival was 58.3±12%. There were no differences in the causes of death between patients with or without ES. A high number of CD34+ cells/kg infused, patients transplanted in early phase, the type of malignancy (solid tumor) and conditioning regimens other than busulfan based were significantly associated with ES in a multivariate analysis.

Extracorporeal photochemotherapy for steroid-refractory graft-versus-host disease in low-weight pediatric patients. Immunomodulatory effects and clinical outcome.

Pediatric patients with refractory graft-versus-host disease (GVHD) have been considered for extracorporeal photochemotherapy (ECP). The main problems with ECP in children, especially in the smaller ones, are technical difficulties of leukaphereses with a large extracorporeal volume. Only a few

ALLOGENEIC CORD BLOOD TRANSPLANTATION IN CHILDREN WITH HEMATOLOGICAL MALIGNANCIES: A Long-Term Follow-Up Single-Center Study

Forty-two consecutive pediatric patients with high-risk leukemia who received cord blood (CB) transplantation at the authors’ institution from January 1996 and December 2007 were included in this study. Age ranged from 6 months to 18 years and body weight from 7 to 73 kg. Twenty-nine patients had ALL and 13 AML. Twenty-seven out of 42 patients were transplanted in advanced phase of disease (beyond 2nd CR). For 13 patients the CB transplantation was their second transplant. The median follow-up for survivors was 60 months (range, 6–120 months). The probability of myeloid engraftment was 95 ± 5% and the median time to neutrophil >500/μL was 20 days (range, 12–54). The median time to platelet engraftment was 60 days (range, 37–200). The probability of relapse was 33 ± 9%. The nonrelapse mortality at day +100 after transplantation was 30 ± 7%. The probability of disease-free survival was 34 ± 7%. The CD34+ cell dose had a significant impact on DFS (HR, 3.28; 95% CI: 1.49–7.23; p =. 003). The results from a long-term follow-up study suggest that cord blood transplantation should be performed in the early phase of disease whenever possible. The cord blood unit for transplantation in pediatric patients with hematological malignancies should be chosen based on cell dose, especially a CD34+ cell dose.

Chemotherapy-related secondary acute myeloid leukemia in patients diagnosed with osteosarcoma.

Secondary acute leukemia (SAL) after treatment of osteosarcoma has been seldom reported in children. Two main mechanisms that can induce SAL have been described. The authors describe two patients who developed SAL after treatment with multiagent therapy. The first patient developed a secondary acute leukemia after treatment with alkylating agents and platinum compounds. The second patient had the clinical and molecular features of a secondary acute leukemia due to topoisomerase II inhibitors. The authors also discuss the data regarding cisplatin-associated SAL. Different molecular and pathogenic agents may be implicated in the development of second malignant neoplasms in long-term survivors of osteosarcomas.

Intentional induction of mixed haematopoietic chimerism as platform for cellular therapy after HLA-matched allogeneic stem cell transplantation in childhood leukaemia patients

Allogeneic peripheral blood stem cell CD34+‐selected transplantation followed by donor lymphocyte infusion (DLI) to maximize graft‐versus‐leukaemia effect while avoiding graft‐versus‐host disease was investigated in 22 paediatric patients with acute myeloid leukaemia (nu2003=u200310) or acute lymphoblastic leukaemia (nu2003=u200312). Patients were grafted with a median (range) 6u2003×u2003106 (2–31u2003×u2003106)/kg CD34+ cells and 1·1u2003×u2003104 (0·2–3·9u2003×u2003104) CD3+ cells. Seventy‐five DLI were performed with no complications. Median time (range) to neutrophil and platelet engraftment was 13 (11–15) and 12u2003d (8–13) respectively. Probability of relapse and disease‐free survival was 23u2003±u20039% and 72u2003±u20036% respectively (median follow‐up of 15u2003months).