Background
The treatment of children with T‐cell lymphoblastic lymphoma (T‐LBL) and precursor B‐cell lymphoblastic lymphoma (pB‐LBL) has improved during the last decades. However, patients with ...relapsed or refractory lymphomas still have a poor prognosis.
Methods
We report the characteristics and evolution of T‐LBL and pB‐LBL relapses in two multicenter prospective studies (LMT 96, European Organization for Research and Treatment of Cancer 58951).
Results
From 1997 to 2008, 194 patients were included in these studies (157 T‐LBL; 37 pB‐LBL); among them, 23 patients underwent relapse or progression (18 T‐LBL and 5 pB‐LBL). The median age was 7.7 years (range 1.4–16.3). The survival rate at 8 years was 8.7% (21 deaths). The median time from diagnosis to relapse was 9 months 1–69 and 11 months 1–45 for T‐LBL and pB‐LBL, respectively. Twenty‐two patients received a second‐line treatment but remission was achieved in only seven patients. In 10 patients, intensification with hematopoietic stem cell transplantation (HSCT) was performed and four of them had a second relapse. Two patients still alive had T‐LBL, experienced relapses 15 and 69 months after diagnosis, and received HSCT. Relapse during the intensive phase and second‐line treatment without HSCT were identified as risk factors for bad prognosis (P = 0.01).
Conclusions
The results of second‐line treatment, including intensive chemotherapy and HSCT, show that salvage treatment is still disappointing in controlling refractory forms. Early identification of patients at high risk of relapse is mandatory, allowing earlier intensification. Valid prognostic parameters, such as biological markers, are needed. International cooperation is warranted to collect more data on these rare diagnoses.
While outcome for pediatric T lymphoblastic lymphoma (T‐LL) has improved with acute leukemia‐type therapy, survival after relapse remains rare. Few prognostic markers have been identified: NOTCH1 ...and/or FBXW7 (N/F) mutations identify good prognosis T‐LL and high‐level minimal disseminated disease (MDD) is reported to be of poor prognosis. We evaluated MDD and/or MRD status by 8‐color flow cytometry and/or digital droplet PCR in 82 pediatric T‐LL treated according to the EURO‐LB02 prednisone reference arm. Both techniques gave identical results for values ≥0.1%, allowing compilation. Unlike historical studies, an MDD threshold of 1% had no prognostic significance. The 54% (42/78) of patients with MDD ≥0.1% had a relatively favorable outcome (5‐y overall survival OS 97.6% versus 80.6%, P = 0.015, 5‐y event‐free‐survival EFS 95.2% versus 80.6%, P = 0.049). MDD lower than 0.1% had no impact in N/F mutated T‐LL, but identified the N/F germline patient with a high risk of relapse. Combining oncogenetic and MDD status identified 86% of patients (n = 49) with an excellent outcome and 14% of N/F germline/MDD <0.1% patients (n = 8) with poor prognosis (5y‐OS 95.9% versus 37.5%, P < 0.001; 5y‐EFS 93.9% versus 37.5%, P < 0.001). If confirmed by prospective studies, MDD and N/F mutational status would allow identification of a subset of patients who merit consideration for alternative front‐line treatment.
Autoimmune cytopenia (AIC) in children may be associated with positive antinuclear antibodies (ANA) and may progress to systemic lupus erythematosus (SLE). We evaluated the risk of progression to SLE ...of childhood-onset ANA-associated AIC. In the French national prospective OBS'CEREVANCE cohort, the long-term outcome of children with ANA-associated AIC (ANA titer ≥1/160) and a subgroup of children who developed SLE were described. ANA were positive in 355 of 1803 (20%) children with AIC. With a median follow-up of 5.8 (range, 0.1-29.6) years, 79 of 355 (22%) patients developed SLE at a median age of 14.5 (1.1-21.4) years; 20% of chronic immune thrombocytopenic purpura, 19% of autoimmune hemolytic anemia, and 45% of Evans syndrome. None of the patients with ANA-negative test developed SLE. Severe manifestations of SLE were observed in 21 patients, and 2 patients died. In multivariate analysis including patients with positive ANA within the first 3 months after AIC diagnosis, age >10 years at AIC diagnosis (relative risk RR, 3.67; 95% confidence interval CI, 1.18-11.4; P = .024) and ANA titer >1/160 (RR, 5.28; 95% CI, 1.20-23.17; P = .027) were associated with the occurrence of SLE after AIC diagnosis. ANA-associated AIC is a risk factor for progression to SLE, especially in children with an initial ANA titer >1/160 and an age >10 years at AIC diagnosis. ANA screening should be recommended in children with AIC, and patients with ANA should be monitored long-term for SLE, with special attention to the transition period. This trial was registered at www.ClinicalTrials.gov as #NCT05937828.
Background
Neonatal atypical hemolytic uremic syndrome (aHUS) is a rare but severe disease that is mainly due to methylmalonic aciduria or genetic complement abnormalities. Traditional management of ...aHUS includes plasma infusion/exchange, but in small or unstable infants, plasma exchange can be challenging because of high extracorporeal volume and difficulty to obtain an adequate venous access. The C5 complement blocker eculizumab has become a cornerstone of first-line management of aHUS due to complement deregulation in older patients. However, little data are available on its use in neonatal aHUS.
Case-diagnosis/treatment
We report on an 11-day-old neonate with severe aHUS (myocardial impairment, respiratory failure, acute kidney disease requiring hemodiafiltration) due to homozygous factor-H deficiency. She received early treatment with eculizumab as first-line therapy and completely recovered within 5 days. A second dose of eculizumab was administered 7 days after the first infusion, followed by a dose every 2 weeks for 2 months and then every 3 weeks, at the same dosage (300 mg). With more than 24 months of follow-up, renal function remains normal.
Conclusions
We report on the long-term efficacy and safety of eculizumab as first-line therapy in neonatal aHUS. However its use still requires optimization in terms of indications and administration (frequency, dosage).
An increased prevalence of syphilis has been observed in many developed countries over the last decade. During pregnancy, syphilis can affect the fetus through development of nonspecific symptoms ...such as microcephaly, ascites, hepatosplenomegaly, dilated and echogenic bowel, placentomegaly, and, uncommonly, fetal hydrops. Congenital syphilis also leads to hematologic abnormalities such as anemia, thrombocytopenia, leukopenia, and leukocytosis. We present a case of nonimmune fetal hydrops with anemia related to syphilis infection. Diagnosis was confirmed by a maternal serological test and microbiological testing on amniotic fluid, umbilical cord, and placental tissues. The patient was treated with penicillin and the fetus received an intrauterine red blood cell transfusion, but fetal death occurred shortly after. Such a presentation is mostly related to parvovirus B19, and syphilis etiology is poorly mentioned because physicians have rarely seen early congenital syphilis in the past. However, given the increasing prevalence of this disease in the adult population, clinicians should remain alert to the various presentations of congenital syphilis.
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