Benefits of rituximab as a second‐line treatment for autoimmune haemolytic anaemia in children: a prospective French cohort study

Childhood autoimmune haemolytic anaemia (AIHA ) requires second‐line immunosuppressive therapy in 30–50% of cases. It appears that rituximab is indicated in such circumstances. This prospective national study reports the practice, efficacy and tolerance of rituximab in children with isolated AIHA and AIHA in the setting of Evans syndrome (ES ). Sixty‐one children were given rituximab between 2000 and 2014. The median interval from diagnosis to rituximab was 9·9 [interquartile range (IQR ) 1·6–28·5] months. Forty‐six patients responded (75%) and the 6‐year relapse‐free survival (RFS ) was 48%. Twenty patients relapsed at a median interval of 10·8 (IQR 3·9–18·7) months, rituximab allowed steroid withdrawal in 44/61 (72%) of children. In isolated AIHA , complete response and 6‐year RFS were significantly higher than in ES (P  < 0·05). Ten out of 61 patients were infants, seven of who responded with a 6‐year RFS of 71%. Among patients without immunoglobulin substitution before rituximab, 4 are still receiving substitutions. Five patients died, including one potentially attributable to rituximab. This large observational series of childhood AIHA established the rituximab benefit‐risk ratio, allowing steroid withdrawal, with 37% of long‐term responders, mainly in isolated AIHA . All subgroups of patients drew benefit. Our long‐term results indicate the baseline to be challenged by new treatment approaches.     

Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients

Many randomized trials have evaluated α-interferon as myeloma therapy, some suggesting a benefit and others not. Most were too small to give reliable answers, so a systematic overview has been performed to provide a more reliable estimate of the effect of interferon. The main end-points were response rates (induction trials), progression-free survival (PFS) and overall survival (OS). Individual patient data were supplied for 24 trials involving 4012 patients, 12 induction trials (2469 patients) and 12 maintenance trials (1543 patients). In induction, response rates were slightly better with interferon (57·5% versus 53·1%, P  = 0·01). PFS was better with interferon (33% versus 24% at 3 years, P  < 0·00001), an effect seen in both induction ( P  = 0·0003) and maintenance ( P  < 0·00001) trials. Median time to progression was increased by about 6 months in both settings. OS was somewhat better with interferon (53% versus 49% at 3 years, P  = 0·01) with median survival increased by about 4 months. This benefit was restricted to the smaller trials. The effect of interferon was not significantly related to the dose or duration of interferon or to patients' characteristics. PFS was improved with interferon, but the survival benefit, if any, was small and needs balancing against cost and toxicity.     

Longitudinal follow up of elevated pulmonary artery pressures in children with sickle cell disease

Elevated pulmonary artery pressures (PAP) occur in approximately 30% of children with sickle cell disease. In adults, pulmonary hypertension is significantly associated with mortality. There are no data on the long term significance in children. Nineteen children with SS/Sß⁰ thalassaemia had elevated PAP, defined as tricuspid regurgitant jet velocity (TRV) ≥2·5 m/s on screening echocardiograms. They were prospectively followed for 23 months (range 19–31 months). Patients with initial TRV ≥ 3 or TRV ≥ 2·5 m/s on repeat echocardiogram had cardiopulmonary evaluation and were offered treatment with hydroxyurea. Associated conditions like asthma and obstructive sleep apnea were treated. 18/19 patients had follow-up echocardiograms. These showed normalization of TRV in 8 patients. Risk factors associated with persistent elevation were higher TRV on initial echocardiogram ( P  = 0·01), lower haemoglobin ( P  = 0·003) and lower oxygen saturation ( P  = 0·03). Five patients with persistently elevated PAP were treated with hydroxyurea. Mean right ventricular pressure dropped from 40·16 to 29·26 ( P  = 0·017) after 3–6 months and to 23·6 mmHg ( P  = 0·002) after 9–12 months on treatment. In conclusion (i) At borderline elevation of TRV there is intrapatient variability and echocardiograms should be repeated for confirmation. (ii) Elevated PAP are reversible in children with early detection and treatment with hydroxyurea.     

Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis

Hairy cell leukaemia (HCL) was first described 50 years ago. Median survival was then 4 years. The purine analogues, introduced in the 1980s, transformed this prognosis. We reviewed data retrospectively from 233 patients, treated with pentostatin ( n  = 188) or cladribine ( n  = 45), to investigate the current long-term outlook. Median follow-up was 16 years. There were no significant differences in outcome between the two agents. Overall, the complete response (CR) rate was 80% and median relapse-free survival was 16 years. After relapse ( n  = 79) or non-response ( n  = 5), 26 patients received pentostatin and 58 cladribine; 69% achieved CR and median relapse-free survival was 11 years. After third-line therapy ( n  = 23), 50% achieved CR and median relapse-free survival was 6·5 years. However, CRs were equally durable, whether after first, second or third-line therapy. Complete responders and those with both haemoglobin >100 g/l and platelet count >100 × 10⁹/l before treatment had the longest relapse-free survival ( P  < 0·0001). Patients still in CR at 5 years had only a 25% risk of relapse by 15 years. Outcomes for patients with recurrent disease improved with the monoclonal antibody rituximab, combined with either purine analogue. Overall only eight patients died of HCL-related causes. Patients achieving a CR can expect a normal lifespan.     

Unrelated stem cell transplantation after reduced intensity conditioning for patients with multiple myeloma relapsing after autologous transplantation

From 2002 to 2007, 49 myeloma patients who relapsed following autologous SCT were included in a prospective multicenter trial to determine the efficacy of a reduced melphalan/fludarabine regimen followed by allogeneic SCT from unrelated donors. All patients showed leucocyte and platelet engraftment after a median of 15 and 19 d, respectively. Grade II–IV acute graft- versus -host disease (GvHD) occurred in 25% of patients and 35% had chronic GvHD. Overall response rate at day 100 was 95% including 46% complete remission (CR). Cumulative incidence of non-relapse mortality at 1 year was 25% [95% confidence interval (CI): 13–37%] and was significantly lower for human leucocyte antigen (HLA)-matched compared to -mismatched SCT (10% vs. 53%, P  = 0·001). The cumulative incidence of relapse at 3 years was 55% (95% CI: 40–70%). After a median follow up of 43 months, the estimated 5-year progression-free and overall survival rates were 20% and 26% respectively and were significantly better for matched in CR at day 100 (41% vs. 7%, P  = 0·04 and 56% vs. 16%, P  = 0·02). We conclude that optimal donor selection is mandatory for a low non-relapse mortality and high relapse incidence, which remains a major concern, should be improved by including post-transplant strategies to upgrade remission status.     

Rituximab therapy in adult patients with relapsed or refractory immune thrombocytopenic purpura: long-term follow-up results

Objective:  To evaluate the long-term activity and toxicity profile of rituximab in adult patients with idiopathic immune thrombocytopenic purpura (ITP).
Patients and methods:  Twenty-six patients with active and symptomatic ITP relapsed or refractory received weekly infusions of rituximab 375 mg/m² for 4 wk. Median time from diagnosis to rituximab was 34.5 months . The following parameters of efficacy and toxicity were considered: complete response (CR) and partial response (PR), relapse rate, relapse-free survival (RFS), therapy-free survival (TFS), short- and long-term toxicity.
Results:  CR and PR were 14/26 (54%) and 4/26 (15%), respectively. Median time of observation was 56.5 months (range 39–77). Nine of the 18 responding patients relapsed after a median of 21 months (range 8–66); 9/26 patients (35%) maintained the response, with a median follow-up of 57 months (range 39–69), and 11/26 (42%) did not necessitate further therapy; estimated 5 yr RFS and TFS were 61% and 72%, respectively. Younger age and shorter interval from diagnosis to rituximab appeared indicators of better outcome. Rituximab administration was associated with two episodes of short-term toxicity, with one case of serum sickness syndrome; no infectious or other significant long-term complications were documented.
Conclusion:  Rituximab therapy may achieve long-lasting remission in nearly one-third of patients with relapsed or refractory ITP, with a good safety profile.     

Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia

Vincristine is a key drug in the treatment of childhood and adult acute lymphoblastic leukemia (ALL), and many other childhood malignancies. Despite decades of wide clinical use, no data on the correlation between vincristine pharmacokinetics and long-term clinical outcome have been published. We here report clinical data (median follow-up time 10·5 years, range 7·3–12 years) for 86 children with B-cell precursor ALL, in whom vincristine kinetics were studied on treatment day 1. The median total plasma clearance was 429 and 331 ml/min per m² and the area under the plasma concentration-time curve (AUC) was 4·49 and 5·40 mg/l × min in relapse and non-relapse patients, respectively (not significant). In standard risk patients, where treatment depends more heavily on vincristine than in other subgroups, the relative risk (RR) of relapse was significantly increased for patients with clearance values above median (RR 5·2; P  = 0·036), or AUC values below median (RR 5·8; P  = 0·025). Our data suggest a relationship between the antileukemic effect and the systemic exposure of the drug, which warrants further studies.     

Prior rituximab correlates with less acute graft-versus-host disease and better survival in B-cell lymphoma patients who received allogeneic peripheral blood stem cell transplantation

Prior therapy with rituximab might attenuate disparate histocompatibility antigen presentation by B cells, thus decreased the risk of acute graft-versus-host disease (GVHD) and improved survival. We tested this hypothesis by comparing the outcomes of 435 B-cell lymphoma patients who received allogeneic transplantation from 1999 to 2004 in the Center for International Blood and Marrow Transplant Research database: 179 subjects who received rituximab within 6 months prior to transplantation (RTX cohort) and 256 subjects who did not receive RTX within 6 months prior to transplantation (No-RTX cohort). The RTX cohort had a significantly lower incidence of treatment-related mortality (TRM) [relative risk (RR) = 0·68; 95% confidence interval (CI), 0·47–1·0; P  =   0·05], lower acute grade II–IV (RR = 0·72; 95% CI, 0·53–0·97; P  =   0·03) and III–IV GVHD (RR = 0·55; 95% CI, 0·34–0·91; P  =   0·02). There was no difference in the risk of chronic GVHD, disease progression or relapse. Progression-free survival (PFS) (RR = 0·68; 95% CI 0·50–0·92; P  =   0·01) and overall survival (OS) (RR = 0·63; 95% CI, 0·46–0·86; P  =   0·004) were significantly better in the RTX cohort. Prior RTX therapy correlated with less acute GVHD, similar chronic GVHD, less TRM, better PFS and OS.     

Long-term follow-up of children with refractory immune thrombocytopenia treated with rituximab

Data on long-term outcomes of children with refractory immune thrombocytopenia (ITP) treated with rituximab are limited. We retrospectively analyzed the long-term effect of rituximab on 22 pediatric ITP patients (11 boys and 11 girls). Compete response (CR) (platelet count ≥100 × 10⁹/L) and partial response (PR) (platelet count 30–99 × 10⁹/L) were achieved in nine (41 %) and two (9 %) patients, respectively. Of the 11 responders, eight subsequently relapsed 2–26 months after initial rituximab treatment. The 5-year relapse-free rate was 14 % (3/22, 95 % confidence interval: 0–27 %) with a median follow-up period of 6.4 years. Five initial responders with subsequent relapse and one non-responder received multiple rituximab treatments of nine courses; all patients responded to the second rituximab therapy without any significant toxicity. All eight patients who relapsed after an initial response and six of 11 non-responders achieved CR or PR with subsequent treatment, including repeated courses of rituximab, splenectomy, steroids, and other immunomodulating agents. Our findings indicated that the sustained effect of rituximab on children with refractory ITP is low, but that the long-term outcome of ITP itself is not poor. Furthermore, repeated rituximab administration may be a promising therapy for those who relapse after an initial response.     

Prediction of survival using absolute lymphocyte count for newly diagnosed patients with multiple myeloma: a retrospective study

Absolute lymphocyte count (ALC) recovery after autologous stem cell transplantation for multiple myeloma (MM) has been reported to be an independent prognostic factor for clinical outcome. The role of ALC on survival in newly diagnosed untreated MM patients is unknown. Between 1994 and 2002, we analysed retrospectively 537 MM patients of 1835 consecutive MM patients that were neither uniformly treated nor part of a clinical trail, but originally diagnosed and followed at the Mayo Clinic. The primary endpoint was to assess the role of ALC at the time of MM diagnosis on overall survival (OS). The median follow-up was 35·1 months (range: 1–152·5 months). ALC, as a continuous variable, was identified as prognostic factor for OS (Hazard ratio = 0·473, 95% confidence interval = 0·359–0·618, P  < 0·0001). MM patients with an ALC ≥1·4 × 10⁹/l experienced superior OS compared with MM patients with an ALC <1·4 × 10⁹/l (65 vs. 26 months, P  < 0·0001). Multivariate analysis identified ALC as an independent prognostic factor for OS. This study showed that, in newly diagnosed MM, ALC is an independent prognostic factor for OS, suggesting a significant role of host immune status in the survival of MM.     

Chlorambucil versus observation after anti-Helicobacter therapy in gastric MALT lymphomas: results of the international randomised LY03 trial

Gastric mucosa-associated lymphoid tissue (MALT) lymphomas are uncommon tumours characterised by a tendency to remain localised for long periods. The aetiological association between MALT lymphomas and Helicobacter pylori is well established. The role of additional chemotherapy after H. pylori eradication in localised MALT lymphomas is unclear. The LY03 trial was designed to establish whether chlorambucil after treatment for H. pylori would help prevent recurrence. Patients were treated with antibiotics for H. pylori infection. Those with successful eradication of H. pylori and no evidence of progression of lymphoma were eligible for randomisation to chlorambucil or observation. Two hundred and thirty-one patients were registered. Ninety-seven percent patients had H. pylori eradicated after antibiotics and 59% achieved macroscopically normal gastric mucosa. One hundred and ten patients were randomised. With a median follow-up of 58 months, six patients were dead and 17 had recurrent/progressive disease. The recurrence/progression rates at 5 years were 11% for chlorambucil, and 21% for observation with a difference of 10%, 95% confidence interval (CI) = −9% to 29%, P  = 0·15. No difference was detected in recurrence/progression-free survival [Hazard Ratio (HR) = 0·96, 95% CI = 0·41–2·2, P  = 0·91] or overall survival (HR = 1·93, 95% CI = 0·39–9·58, P  = 0·42). This is the first randomised trial to show there is no good evidence to support that additional single agent chemotherapy to anti -H. pylori treatment contributes to prevent recurrence in localised gastric MALT lymphomas.     

Postpolycythaemic myelofibrosis: frequency and risk factors for this complication in 116 patients

Postpolycythaemic myelofibrosis (PPMF) is a known complication of polycythaemia vera (PV) but information regarding its incidence and predisposing factors is not well defined. In 116 subjects consecutively diagnosed with PV in a single institution (median age 62 years, range: 20–88), the probability of PPMF was analysed by the Kaplan–Meier method, followed by the log-rank test. With a mean follow-up of 8 years (95% confidence interval: 6·6–9), 17 patients had evolved into PPMF (15%). The probability of evolution to PPMF was 16% at 10 years and 34% at 15 years. Age, gender, spleen size, leucocytosis, thrombocytosis or cytoreductive treatment were not associated with an increased risk of PPMF. The actuarial probability of PPMF at 15 years was higher in those patients presenting at diagnosis with endogenous megakaryocytic colony formation (59% when present versus 10% when absent, P  = 0·03), an elevated serum lactate dehydrogenase (LDH) level (69% vs. 23% in patients with normal LDH, P  = 0·04), and in those who were heterozygous for the JAK2 V617F mutation (55% vs. 17% in heterozygotes, P  = 0·04). In conclusion, PPMF is a frequent complication in PV patients at 15 years with the risk being higher in patients with increased LDH, endogenous megakaryocytic colony formation or a high JAK2 V617F allele burden.     

Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993

The predictive value of molecular minimal residual disease (MRD) monitoring using polymerase chain reaction amplification of clone-specific immunoglobulin or T-cell Receptor rearrangements was analysed in 161 patients with non T-lineage Philadelphia-negative acute lymphoblastic leukaemia (ALL) participating in the UK arm of the international ALL trial UKALL XII/Eastern Cooperative Oncology Group (ECOG) 2993. MRD positivity (≥10⁻⁴) in patients treated with chemotherapy alone was associated with significantly shorter relapse-free survival (RFS) at several time-points during the first year of therapy. MRD status best discriminated outcome after phase 2 induction, when the relative risk of relapse was 8·95 (2·85–28·09)-fold higher in MRD-positive (≥10⁻⁴) patients and the 5-year RFS 15% [95% confidence interval (CI) 0–40%] compared to 71% (56–85%) in MRD-negative (<10⁻⁴) patients ( P  = 0·0002) When MRD was detected prior to autologous stem cell transplantation (SCT), a significantly higher rate of treatment failure was observed [5-year RFS 25% (CI 0–55%) vs. 77% (95% CI 54–100%) in MRD-negative/<10⁻⁴, P  = 0·01] whereas in recipients of allogeneic-SCT in first complete remission, MRD positivity pre-transplant did not adversely affect outcome. These data provide a rationale for introducing MRD-based risk stratification in future studies for the delineation of those at significant risk of treatment failure in whom intensification of therapy should be evaluated.     

Bortezomib, low-dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma

This multicenter phase I/II study investigated the maximum tolerated dose (MTD), safety, and efficacy of low dose intravenous (IV) melphalan in combination with bortezomib for patients with relapsed multiple myeloma (MM). Patients received bortezomib 1·3 mg/m² on days 1, 4, 8, and 11 and escalating doses of IV melphalan (2·5–10·0 mg/m²) on day 2 of a 28-day cycle for a maximum of eight cycles. Dexamethasone 20 mg was added for progressive or stable disease. Fifty-three patients were enrolled. The MTD was defined at melphalan 7·5 mg/m² and bortezomib 1·3 mg/m². The overall response rate (ORR) was 68% (23% complete or near-complete responses [CR/nCR]) whilst at the MTD ( n  = 33) the ORR was 76% (34% CR/nCR). After median follow-up of 17 months, the median progression free survival was 10 months, rising to 12 months at the MTD ( P  < 0·05 vs. non-MTD regimens). The median overall survival was 28 months, but was not yet reached at the MTD. Grade 3/4 adverse events included thrombocytopenia (62%), neutropenia (57%), infection (21%), and neuropathy (15%). Bortezomib and low-dose IV melphalan combination therapy is a safe and highly effective regimen for patients with relapsed MM. These data suggest further investigation of this combination is warranted.     

Efficacy of a combination of human recombinant erythropoietin + 13-cis-retinoic acid and dihydroxylated vitamin D3 to improve moderate to severe anaemia in low/intermediate risk myelodysplastic syndromes

The efficacy of human recombinant erythropoietin (rEPO) in myelodysplastic syndromes (MDS) has generally been best in untransfused patients with 'refractory anaemia' according to the World Health Organization (WHO). We treated 63 MDS patients [excluding refractory anaemia with excess blasts, type 2 (RAEB2)] with a previously tested combination of 13- cis -retinoic acid and dihydroxylated vitamin D3 ± 6-thioguanine in addition to rEPO. Most patients were categorized as refractory cytopenia with multilineage dysplasia and RAEB1, with intermediate 1 International Prognostic Scoring System (IPSS) score; all had Hb <95 g/l, and 70% required regular erythrocyte transfusions. Treatment was well tolerated, and erythroid response rate according to new International Working Group criteria was 60%: 50% in RAEB1 and 64% in non-RAEB patients ( P  = 0·383). Response rate was not affected by transfusion requirement (63%; 58% in untransfused), IPSS and WHO Prognostic Scoring System scores, and weekly rEPO dosage (30–50 000 U vs. 80 000 U). Median response duration was 16 months. Median survival reached 14 months for RAEB1 and 55 months for non-RAEB patients, with a significant difference in the latter between responders and non-responders (median 82 months vs. 44 months; P  = 0·036). Our combined therapy, independent of rEPO dosage, achieved in patients with unfavourable response predictors, a rate of anaemia improvement comparable to the best obtained in lower risk patients by high-dose rEPO.     

Treatment of primary refractory and relapsed acute lymphoblastic leukaemia in children and adults: the GIMEMA/AIEOP* experience

One hundred and forty-seven patients aged <55 years with advanced acute lymphoblastic leukaemia (ALL) were enrolled in an Italian cooperative study (ALL R-87), This protocol consists of an induction phase with idarubicin (IDA) plus intermediate-dose cytarabine (IDARA-C), followed by a consolidation phase and bone marrow transplant (BMT). Complete remission (CR) was achieved in 97/147 patients (66%) with a CR rate of 77% in children versus 51% in adults ( P <0·01), 48 responders (50%) underwent BMT.
Probability of event-free survival (EFS ± SE) was 10·2±3·1% at 56 months. EFS was 14·3±4·51% at 56 months for children versus 3·8±3·41% at 37 months for adults ( P <0·0001). Among patients treated in first relapse, EFS was 14·2±7·79% for patients with CR >18 months versus 6·6±3·17% for those with CR <18 months ( P <0·0001).
Projected disease-free survival (DFS ±SE) was 15·4±4·61% at 55 months for all responders and 43·3±14·34% at 52 months for allografted patients. Projected overall probability of survival ±SE for all patients was 18·8±4·13% at 56 months.
This study confirms the efficacy of IDA plus IDARA-C in poor-risk ALL patients. A more intensive post-remission therapy or alternative approach must be designed to improve long-term results.     

Extended triple intrathecal therapy in children with T-cell acute lymphoblastic leukaemia: a report from the Israeli National ALL-Studies

Owing to the increased central nervous system (CNS) relapse risk in T-cell acute lymphoblastic leukaemia (ALL), it is unclear whether preventive cranial radiation (pCRT) can be safely omitted. In this study, pCRT was replaced by extended triple intrathecal therapy (TIT) in prednisone good early responders – medium-risk (MR) group, accounting for 76% of T-ALL patients. From 1989 to 2003, 143 T-ALL patients aged 1–18 years were enrolled in the Israel National Studies (INS) 89 ( n  = 84) and INS 98 ( n  = 59) trials, based on ALL-Berlin–Frankfurt–Munster (BFM) 86/90 and ALL-BFM 95 protocols, respectively. Five-year event-free survival (EFS) of the MR group in the INS 89 ( n  = 60) was 70 ± 5·9% and the INS 98 ( n  = 43), 83·7 ± 5·6% ( P  = 0·12); the cumulative incidence (CI) of any CNS relapse was 5·0 ± 2·8% and 2·3 ± 2·3% ( P  = 0·50), respectively. There was no difference in outcome between MR patients with a white blood cell count (WBC) ≥100 × 10⁹/l treated with extended TIT ( n  = 17) or pCRT ( n  = 10). For all T-ALL patients, 5-year EFS was 61·9 ± 5·3% in INS 89 and 72·9 ± 5·8% in INS 98, ( P  = 0·21); the CI of any CNS relapse was 7·1 ± 2·8% and 1·7 ± 1·7% ( P  = 0·142), respectively. Outcome of T-ALL MR patients given extended TIT in the context of BFM-based protocols with long-term follow-up appeared to be comparable to studies in which a larger proportion of patients was irradiated, and was associated with low risk of CNS relapse, regardless of the WBC.     

Possible lower rate of chronic ITP after IVIG for acute childhood ITP an analysis from registry I of the Intercontinental Cooperative ITP Study Group (ICIS)

In children, one-third of immune thrombocytopenic purpura (ITP) patients follow a chronic course. The present study investigated whether treatment with intravenous immunoglobulin (IVIG) at the time of diagnosis of ITP is of prognostic significance, using data from 1984 children entered in Registry I of the Intercontinental Cooperative ITP Study Group. A matched pairs analysis compared children with thrombocytopenia (platelet count <150 × 10⁹/l) 6 months following diagnosis with children whose platelet count was normal 6 months after diagnosis. It was found that children initially treated with IVIG were more likely to have a normal platelet count 6 months after diagnosis than children not receiving IVIG (odds ratio 1·81; 95% confidence interval: 1·25–2·64). This result was independent of age, gender, country of origin, platelet count at diagnosis or infection preceding the diagnosis of ITP. In a similar analysis, comparing children with a platelet count <50 × 10⁹/l 6 months after diagnosis with children whose platelet count was ≥50 × 10⁹/l at that time point, the former group was less often treated with IVIG than with steroids ( P  = 0·02). Prospective studies are required to further explore this potential effect of IVIG.     

Mental and motor development before and during growth hormone treatment in infants and toddlers with Prader-Willi syndrome

Background  Prader–Willi syndrome (PWS) is a neurogenetic disorder characterized by muscular hypotonia, psychomotor delay, feeding difficulties and failure to thrive in infancy. GH treatment improves growth velocity and body composition. Research on the effects of GH on psychomotor development in infants with PWS is limited.
Objective  To evaluate psychomotor development in PWS infants and toddlers during GH treatment compared to randomized controls.
Design/patients  Forty-three PWS infants were evaluated at baseline. Twenty-nine of them were randomized into a GH group ( n  = 15) receiving 1 mg/m²/day GH or a non-GH-treated control group ( n  = 14). At baseline and after 12 months of follow-up, analysis with Bayley Scales of Infant Development II (BSID-II) was performed. Data were converted to percentage of expected development for age (%ed), and changes during follow-up were calculated.
Results  Infants in the GH group had a median age of 2·3 years [interquartile range (IQR) 1·7–3·0] and in the control group of 1·5 years (IQR 1·2–2·7) ( P =  0·17). Both mental and motor development improved significantly during the first year of study in the GH group vs. the control group: median (IQR) change was +9·3% (–5·3 to 13·3) vs. –2·9% (–8·1 to 4·9) ( P  < 0·05) in mental development and +11·2% (–4·9 to 22·5) vs. –18·5% (–27·9 to 1·8) ( P  < 0·05) in motor development, respectively.
Conclusion  One year of GH treatment significantly improved mental and motor development in PWS infants compared to randomized controls.     

Rituximab (Anti-cd20 Monoclonal Antibody) in Children with Chronic Refractory Symptomatic Immune Thrombocytopenic Purpura: Efficacy and Safety of Treatment

This retrospective study investigated the effects of rituximab in 19 pediatric patients (15 girls and 4 boys) with chronic refractory symptomatic immune thrombocytopenic purpura (ITP). Patients received from 2 to 5 weekly infusions of rituximab (375 mg/m(2)); 15 patients were younger than 12 years when treated. The median follow-up time was 30 months (range, 9-43 months). The overall response rate was 68% (13/19 patients). Six responders relapsed at a median of 4.5 months (range, 3-8 months). Seven patients still displayed a platelet count >150,000/microL at a median of 33 months (range, 14-43 months) after rituximab treatment. Six of 15 patients treated with 4 or 5 weekly infusions and 1 of 4 patients treated with 2 or 3 infusions are still in remission. No difference was detected between splenectomized and nonsplenectomized patients. The duration of ITP disease at the time of treatment did not influence the response rate. Patients still in remission showed significantly lower levels of CD19+ cells after 4 and 6 months than nonresponding or relapsed patients (P < .05). No major infections were reported during follow-up. Our data show the efficacy and tolerability of rituximab in young children with refractory symptomatic ITP. Nonrelapsed patients showed a more prolonged B-cell depletion.