Introduction
In order to describe relapsed B‐cell non‐Hodgkin lymphoma and mature acute leukemia in children/adolescents treated with the Lymphomes Malins B (LMB) regimen and their outcome in the ...rituximab era, relapses in the French LMB2001 study were reviewed.
Methods
Between February 2001 and December 2011, 33 patients out of 773 (4.3%) relapsed; 27 had Burkitt lymphoma and six large B‐cell histology. Median age at diagnosis was 10.1 years. One patient was initially treated in risk group A, 21 in group B, and 11 in group C.
Results
Median time to relapse after diagnosis was 4.5 months (range 2.4‐13.6). Thirty‐two patients received salvage therapy. Twenty‐seven received rituximab mainly in addition to high‐dose cytarabine and etoposide (n = 18) and/or ifosfamide, carboplatin, and etoposide (n = 7). First‐line salvage chemotherapy response rate was 66% with 47% being complete remission (CR). Twenty‐one patients received high‐dose chemotherapy (HDC) followed by autologous (n = 13) or allogeneic (n = 8) transplant. With a median follow‐up of 6.8 years, the 5‐year survival rate after relapse was 36.4% (95% confidence interval CI 22‐53%). Twelve patients were still alive; all but one (group A) received consolidation treatment. Achieving CR before consolidation was significantly associated with better survival, with a 5‐year survival rate of 75% (95% CI 46.8‐91.1%) for patients in CR before HDC, 33% (95% CI 9.7‐70%) for patients in partial remission, and 0% for nonresponders (P = .033).
Conclusion
Survival of children/adolescents with mature B‐cell lymphoma/leukemia remains poor after relapse with no apparent improvement with rituximab. Response rates to salvage chemo‐immunotherapies are insufficient and new drugs are urgently needed to improve disease control.
In anaplastic lymphoma kinase (ALK)‐positive anaplastic large cell lymphoma (ALK+ ALCL), positive minimal residual disease (MRD+) after the first chemotherapy course was proven of strong prognostic ...significance. We aimed to validate these results in 138 French patients. Eighty‐seven patients had a detectable minimal disseminated disease at diagnosis (MDD+). Early MRD assessment was performed in 33 of 87 patients and was positive in 18 and negative in 15 (MRD−). Three‐year progression‐free survival was significantly correlated with the MDD/MRD status: 81.1% in MDD−, 69.6% in MDD+/MRD−, and 15.2% in MDD+/MRD+ patients. In conclusion, we confirmed on an independent cohort that the MDD/MRD status has strong prognosis significance in ALK+ ALCL.
Primary Mediastinal large B-cell Lymphoma (PMLBL) is a rare entity predominantly affecting adolescents and young adults. Recently, an international phase 2 trial in pediatric patients using ...dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) failed to reproduce excellent survival reported in some adult studies. The optimal therapy regimen needs to be determined in this disease. French prospective LMB2001 trial included all patients < 18 years with mature B-cell lymphoma treated in French centers. For patients with PMLBL, treatment included 4 to 8 courses of Lymphomes Malins B (LMB)-based chemotherapy without radiotherapy. From 2008, rituximab was added before each chemotherapy course. From 09/2001 to 03/2012, 42 patients with PMLBL were registered. The median age was 15 years (range 8-18). 21 patients were treated by chemotherapy plus rituximab. The median follow-up was 7.1 years (Interquartile range, 5.8-11.1). Five-year event-free (EFS) and overall survival (OS) were 88.1% (95%Confidence Interval (CI), 75.0%-94.8%) and 95.2% (95%CI, 84.0%-98.7%) for the whole population. The 5-year EFS was 81.0% (95%CI, 60.0%-92.3%) and 95.2% (95%CI, 77.3%-99.2%) (HR=0.24 (95%CI 0.03-2.2)) and 5-year OS was 90.5% (95%CI, 71.1%-97.3%) and 100% for patients treated without and with rituximab, respectively. Only 1/21 patients treated with rituximab and LMB-based chemotherapy had local early treatment failure but achieved prolonged complete remission with second-line chemotherapy and radiotherapy. Intensive LMB-based chemotherapy with rituximab achieved excellent survival in children/adolescents with PMLBL. Further international prospective studies are required to confirm these results in this population.
Sickle cell disease (SCD) induces chronic haemolytic anaemia and intermittent vaso-occlusion that results in tissue ischaemia causing acute, severe pain episodes that can lead to frequent ...hospitalizations. These consequences can have repercussions on family, social, school and/or professional life. Here, we present some of the results of the PHEDRE study (Pharmacodépendance Et DREpanocytose-drug dependence and sickle-cell disease), which is the largest study of patients with SCD in France. This paper intends to describe characteristics of the French SCD population. We also aimed to assess the impact of the disease on the lives of patients using objective and subjective variables.
The PHEDRE study was a national multicentric observational study. Adults, adolescents and children with a confirmed SCD diagnosis were included in the study by their referring doctor. Then, they were interviewed by phone about their socioeconomic status, about the impact of the disease on their lives and about their analgesic and psychoactive drug use.
The study population consisted of 872 patients (28% were minors). Seventy-two percent of adults were active, and all minors were in school. Many patients presented criteria of severe SCD. Seventy-five percent were homozygous SS, 15% were double heterozygotes SC and 8% were heterozygotes Sβthal, 87% received specific treatment, 58% were hospitalized at least once for vaso-occlusive crisis in the past 12 months, and the number of analgesic drugs taken averaged 3.8. Seventy-five percent of patients reported academic or professional consequences related to their SCD, and 52% reported social consequences.
The impact of SCD on patients' lives can be significant, nevertheless their social integration seems to be maintained. We highlighted respect of recommendations regarding analgesic treatments and only a few patients used tobacco, alcohol or cannabis.
Clinical Trials, NCT02580565; https://clinicaltrials.gov/ Registered 16 October 2015.
Background
Thanks to an improved therapeutic regimen in childhood B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), 5 year‐overall survival now exceeds 90%. Unfortunately, the 25% of children ...who relapse have an initial poor prognosis, potentially driven by pre‐existing or emerging molecular anomalies. The latter are initially and essentially identified by cytogenetics. However, some subtle alterations are not visible through karyotyping.
Methods
Single nucleotide polymorphisms (SNP) array is an alternative way of chromosomal analysis allowing for a more in‐depth evaluation of chromosomal modifications such as the assessment of copy number alterations (CNA) and loss of heterozygosity (LOH). This method was applied here in retrospective diagnosis/relapse paired samples from seven children with BCP‐ALL and in a prospective cohort of 38 newly diagnosed childhood cases.
Results
In the matched study, compared to the initial karyotype, SNP array analysis reclassified two patients as poor prognosis cases. Modulation during relapse was seen for 4 CNA and 0.9 LOH. In the prospective study, SNP reclassified the 10 patients with intermediate karyotype as 7 good prognosis and 3 poor prognosis. Ultimately, in all the children tested, SNP array allowed to identify additional anomalies compared to conventional karyotype, refine its prognostic value and identify some druggable anomalies that could be used for precision medicine. Overall, the anomalies detected could be segregated in four groups respectively involved in B‐cell development, cell proliferation, transcription and molecular pathways.
Conclusion
SNP therefore appears to be a method of choice in the integrated diagnosis of BCP ALL, especially for patients initially classified as intermediate prognosis. This complementary method of both cytogenetics and high throughput sequencing allows to obtain further classified information and can be useful in case of failure of these techniques.
Single nucleotide polymorphisms array allowed to better perform risk‐classification for 45 patients with acute lymphoblastic leukemia.
In many countries, nitrous oxide is used in a gas mixture (EMONO) for short-term analgesia. Cases of addiction, with significant misuse, have been reported in hospitalized patients. Patients ...suffering from sickle cell disease (SCD) could represent a high-risk population for substance use disorder (SUD) due to their significant pain crisis and repeated use of EMONO. The objective of the PHEDRE study was to assess the prevalence of SUD for EMONO in French SCD patients.
A total of 993 patients were included. Among 339 EMONO consumers, only 38 (11%) had a SUD, with very few criteria, corresponding mainly to a mild SUD due to a use higher than expected (in quantity or duration) and relational tensions with the care teams. Almost all patients (99.7%) were looking for an analgesic effect, but 68% of patients were also looking for other effects. The independent risks factors associated with at least one SUD criterion were: the feeling of effects different from the expected therapeutic effects of EMONO, at least one hospitalization for vaso occlusive crisis in the past 12 months and the presence of a SUD for at least one other analgesic drug.
The use of EMONO was not problematic for the majority of patients. Manifestations of SUD that led to tensions with healthcare teams should alert and lead to an evaluation, to distinguish a true addiction from a pseudoaddiction which may be linked to an insufficient analgesic treatment related to an underestimation of pain in SCD patients.
Clinical Trials, NCT02580565. Registered 16 October 2015, https://clinicaltrials.gov/.
Introduction
The heterozygous condition for β‐thalassemia mutation associated with an extra functional α‐globin gene can produce a Thalassemia Intermedia (TI) phenotype. This genotype is the second ...in frequency in the French Thalassemia Registry NaThalY that prospectively collects laboratory and clinical data.
Materials and Methods
The present report analyses transfusion needs, iron overload (ferritin, hepatic and cardiac iron concentrations), and complication rates in 45 patients included in NaThalY and presenting a heterozygous β0 or β+‐thalassemia mutation associated with a triplication at HBA locus. This cohort was compared to a cohort of patients with TI due to mutations in the beta‐globin gene only and included in the French registry.
Results
Patients with an extra functional α‐globin gene showed a less severe anemia, lower transfusion needs and lower complication rates than those with TI related to the β‐globin gene only. Nevertheless, some of them displayed complications such as cholelithiasis or extramedullary hematopoiesis. In addition, one third of the cohort needed transfusions and another third was under iron chelation.
Conclusion
The genotype associating a heterozygous β0 or β+‐thalassemia mutation with a triplication at HBA locus should be accurately diagnosed as it could lead to symptomatic anemia and to potential iron overload and iron‐related complications even in patients with no transfusion need.
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