The objective of the present study was to investigate the role of early common infections and perinatal characteristics in the aetiology of childhood common leukaemia. A case-control study was ...conducted from 1995 to 1998 in France, and included 473 incident cases of acute leukaemia (AL) (408 acute lymphoblastic leukaemia (ALL), 65 acute myeloid leukaemia (AML) age-, sex- and region-matched with 567 population-based controls. Data on the medical history of the child and his/her environment were collected using self-administered questionnaires. Analyses were conducted using nonconditional logistic regression. A slight negative association with early infections was observed (OR=0.8; 95% CI (0.6-1.0)). The association was stronger for early gastrointestinal infections. Early day-care was found to be associated with a decreased risk of AL (OR=0.6; 95% CI (0.4-0.8) and OR=0.8; 95% CI (0.5-1.2) for day-care starting before age 3 months and between 3 and 6 months, respectively). No association with breast-feeding was observed, irrespective of its duration. A birth order of 4 or more was associated with a significantly increased risk of AL (OR=2.0; 95% CI (1.1-3.7) with ALL). A history of asthma was associated with a decreased risk of ALL (OR 0.5; 95% CI (0.3-0.90). Although the results regarding birth order and breast-feeding do not fit with Greaves' hypothesis, the study supports the hypothesis that early common infections may play a protective role in the aetiology of childhood leukaemia, although this effect was not more marked for common ALL.
Background: The development of an inhibitor is the major complication facing patients with hemophilia A treated by administration of factor (F) VIII concentrates. Restoration of tolerance to FVIII ...can be achieved by prolonged administration of FVIII (immune tolerance induction, ITI). Although ITI has been used for more than 30 years in patients with hemophilia A and inhibitor, its mechanism of action is still poorly understood. Objectives: As administration of high doses of antigen can induce the apoptosis of the T cells recognizing the antigen, a potential mechanism of action of ITI may be the deletion of FVIII‐specific T cells. Patients/Methods: We studied the CD4+ T‐cell response to FVIII in five (one mild, one moderate and three severe) patients successfully desensitized by administration of FVIII and in control subjects. Results: Following repeated stimulation with autologous dendritic cells loaded with FVIII, FVIII‐specific T oligoclonal cell lines were expanded from the blood of one of the successfully desensitized patients. The FVIII‐specific T cells produced IL‐5, IL‐13 and IL‐2. By contrast, FVIII‐specific T‐cell lines could not be derived from three patients with mild hemophilia A without inhibitor or from four normal control subjects. Conclusions: These data represent the first analysis of the cellular mechanisms regulating the induction of tolerance to FVIII. They demonstrate that successful tolerance induction may occur without deletion of FVIII‐specific T cells.
From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucémie Aiguë Myéloblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This ...intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 60+/-4 and 48+/-4%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 52+/-4% for non-allografted patients and 57+/-7% for allografted patients (P=NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MT-) than in patients randomized for MT (77.6+/-8 vs 59+/-8%; P=0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.
The aim of this study was to show that steroid therapy taken before the diagnosis of acute lymphoblastic leukemia (ALL) can alter the management of the disease.
We conducted a multicenter ...retrospective study on 11 children treated between 2005 and 2011, who received oral steroids ranging from 0.6 to 3.3mg/kg/day prednisolone equivalent for a duration of 2 to 15 days during the 2 months prior to diagnosis of ALL.
Four children had febrile pancytopenia. Among them, 2 had severe infections and a noncontributive bone marrow aspiration. One of them presented a severe tumoral lysis syndrome and was hospitalized twice in the intensive care unit. Two teenagers had central nervous system involvement at diagnosis of T-ALL, 1 having associated cutaneous locations, the second one showing pulmonary and central nervous system (CNS) leukostasis with renal failure and disseminated intravascular coagulation. One child died of septic shock during the induction phase of steroid-resistant T-ALL. Four children had no complications during the induction phase. Steroid resistance occurred in 5 cases and steroid sensitivity could not be evaluated in 3 cases. Three allogeneic bone marrow transplants were performed: the first one because of early CNS relapse, the 2 others because of initial treatment resistance.
Steroids can induce a delay in the management of ALL and seem to favor initial complications, and possibly increase diffuse locations as well as steroid resistance. Their prescription needs to be carefully managed, especially for uncharacteristic infectious symptoms. Then a complete blood count should be done.
Montrer qu’une corticothérapie avant le diagnostic de leucémie aiguë lymphoblastique (LAL) peut entraîner des difficultés dans la prise en charge de la maladie.
Étude rétrospective de 2005 à 2011, ...multicentrique sur 11 enfants ayant reçu une corticothérapie orale à la dose de 0,6 à 3,3mg/kg/j d’équivalent prednisolone pendant 2 à 15 jours dans les deux mois précédant le diagnostic de LAL.
Quatre enfants s’étaient présentés avec une pancytopénie fébrile, dont 2 avec un sepsis sévère et un myélogramme initial ne permettant pas le diagnostic en temps utile. L’un d’entre eux avait souffert d’un syndrome de lyse brutale et séjourné à deux reprises en réanimation. Une atteinte méningée avait été observée chez 2 adolescents ayant une LAL-T, avec des lésions cutanées pour l’un, une leucostase cérébrale et pulmonaire, avec insuffisance rénale et coagulation intravasculaire disséminée (CIVD) pour l’autre. Une enfant était décédée d’un choc septique lors de l’induction d’une LAL-T corticorésistante. Quatre enfants n’avaient présenté aucune complication pendant l’induction. Une corticorésistance avait été notée chez 5 enfants, alors que la réponse aux corticoïdes n’était pas évaluable chez 3 autres enfants. Trois allogreffes de moelle avaient été réalisées : la première pour une rechute méningée précoce et les 2 autres pour des LAL-T réfractaires à l’induction.
Les corticoïdes peuvent être à l’origine d’un retard à la prise en charge de la LAL et semblent majorer les complications initiales, voire favoriser des atteintes diffuses ainsi qu’une corticorésistance ultérieure. La prudence est donc requise quant à leur prescription notamment devant des tableaux cliniques infectieux peu spécifiques, pour lesquels une numération formule sanguine (NFS) est particulièrement recommandée.
The aim of this study was to show that steroid therapy taken before the diagnosis of acute lymphoblastic leukemia (ALL) can alter the management of the disease.
We conducted a multicenter retrospective study on 11 children treated between 2005 and 2011, who received oral steroids ranging from 0.6 to 3.3mg/kg/day prednisolone equivalent for a duration of 2 to 15 days during the 2 months prior to diagnosis of ALL.
Four children had febrile pancytopenia. Among them, 2 had severe infections and a noncontributive bone marrow aspiration. One of them presented a severe tumoral lysis syndrome and was hospitalized twice in the intensive care unit. Two teenagers had central nervous system involvement at diagnosis of T-ALL, 1 having associated cutaneous locations, the second one showing pulmonary and central nervous system (CNS) leukostasis with renal failure and disseminated intravascular coagulation. One child died of septic shock during the induction phase of steroid-resistant T-ALL. Four children had no complications during the induction phase. Steroid resistance occurred in 5 cases and steroid sensitivity could not be evaluated in 3 cases. Three allogeneic bone marrow transplants were performed: the first one because of early CNS relapse, the 2 others because of initial treatment resistance.
Steroids can induce a delay in the management of ALL and seem to favor initial complications, and possibly increase diffuse locations as well as steroid resistance. Their prescription needs to be carefully managed, especially for uncharacteristic infectious symptoms. Then a complete blood count should be done.
Discovering chronic illnesses in children initially shatters the family balance and triggers emotional reactions.
We retrospectively report parents' experiences and emotional reactions to learning ...the diagnosis of hemophilia in their children. Twenty-six parents (18 mothers, 8 fathers) of 24 hemophiliac A or B children (major n=8, moderate n=6, mild n=10), aged from 0 to 18 years, were individually asked to answer a separate questionnaire for each child during a systematic consultation. We obtained 29 completed questionnaires.
The diagnostic circumstances were a major bleeding episode (n=8), frequent hematomas (n=4), preoperative blood sample (n=4), and familial screening (n=8). In 9 cases, both parents were informed of the diagnosis at the same time and in 13 cases, the mother was alone. The most frequent feelings were future apprehension (n=20), initial shock reaction (n=18), anxiety (n=12), and guilt (n=10) expressed by mothers only. Parents' emotional states were neither correlated with the severity of the disease nor with the diagnostic circumstances. All parents questioned reported being satisfied with the quality of the initial information.
The crisis generated by learning the diagnosis of a chronic disease in their children warrants delivering initial information to both parents at the same time, especially in hemophilia since mothers tend to be more concerned.
La découverte d’une pathologie chronique chez l’enfant bouleverse l’équilibre familial préexistant et génère des réactions émotionnelles dans la famille.
Il s’agit d’une étude rétrospective ...rapportant le vécu de parents de l’annonce du diagnostic d’hémophilie chez leur(s) enfant(s). Vingt-six parents (18 mères et 8 pères) de 24 enfants hémophiles A ou B (majeurs
n
=
8, modérés
n
=
6, mineurs
n
=
10) ont été interrogés lors d’une consultation de suivi, pour chaque enfant d’âge différent, représentant un total de 29 témoignages.
Les circonstances de diagnostic étaient : un accident hémorragique (
n
=
8), des hématomes fréquents (
n
=
4), un bilan préopératoire (
n
=
4), un dépistage familial (
n
=
8). L’annonce avait été faite aux 2 parents ensemble (
n
=
9), ou à la mère seule (
n
=
13). La « peur de l’avenir » (
n
=
20) et le choc (
n
=
18) étaient les affects les plus fréquemment cités, suivis par l’angoisse (
n
=
12) et la culpabilité (
n
=
10) uniquement exprimée par les mères. Tous les parents interrogés se sont dits satisfaits de la qualité des informations initiales.
Le traumatisme engendré par l’annonce d’une maladie chronique justifie de réunir les 2 parents dès l’entretien initial, particulièrement pour l’hémophilie, les mères tendant à s’impliquer davantage dans la prise en charge.
Discovering chronic illnesses in children initially shatters the family balance and triggers emotional reactions.
We retrospectively report parents’ experiences and emotional reactions to learning the diagnosis of hemophilia in their children. Twenty-six parents (18 mothers, 8 fathers) of 24 hemophiliac A or B children (major
n
=
8, moderate
n
=
6, mild
n
=
10), aged from 0 to 18 years, were individually asked to answer a separate questionnaire for each child during a systematic consultation. We obtained 29 completed questionnaires.
The diagnostic circumstances were a major bleeding episode (
n
=
8), frequent hematomas (
n
=
4), preoperative blood sample (
n
=
4), and familial screening (
n
=
8). In 9 cases, both parents were informed of the diagnosis at the same time and in 13 cases, the mother was alone. The most frequent feelings were future apprehension (
n
=
20), initial shock reaction (
n
=
18), anxiety (
n
=
12), and guilt (
n
=
10) expressed by mothers only. Parents’ emotional states were neither correlated with the severity of the disease nor with the diagnostic circumstances. All parents questioned reported being satisfied with the quality of the initial information.
The crisis generated by learning the diagnosis of a chronic disease in their children warrants delivering initial information to both parents at the same time, especially in hemophilia since mothers tend to be more concerned.
To determine whether the use of a recombinant human granulocyte colony-stimulating factor (G-CSF lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation ...chemotherapy of childhood acute lymphoblastic leukemia (ALL).
Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval).
CDI was significantly increased in the G-CSF group compared with the non-G-CSF group (mean +/- 95% confidence interval, 105 +/- 5% v 91 +/- 4%; P <.001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups.
G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.
PDF
