High-dose phenobarbital therapy in term newborn infants with severe perinatal asphyxia: A randomized, prospective study with three-year follow-up

1998 ◽  
Vol 132 (2) ◽  
pp. 345-348 ◽  
Author(s):  
Robert T. Hall ◽  
Fred K. Hall ◽  
Donna K. Daily
Keyword(s):  
Prospective Study ◽  
Perinatal Asphyxia ◽  
Newborn Infants ◽  
High Dose ◽  
Term Newborn

scholarly journals Retrospective and Prospective Study of Childhood Autoimmune Hemolytic Anemia. a Preliminary Report from the Red Cell Working Group of the Paediatric Hemato-Oncology Italian Associations (AIEOP)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 947-947
Author(s):  
Saverio Ladogana ◽  
Raffaella Colombatti ◽  
Silverio Perrotta ◽  
Angela Maggio ◽  
Matteo Maruzzi ◽  
...  
Keyword(s):  
Partial Response ◽  
Prospective Study ◽  
Autoimmune Hemolytic Anemia ◽  
Complete Response ◽  
High Dose ◽  
Red Cell ◽  
Line Treatment ◽  
Secondary Form ◽  
Hb Concentration

Autoimmune hemolytic anemia (AIHA) is an uncommon disease of childhood caused by the premature destruction of erythrocytes by autoantibodies. In this rare disease both diagnostic criteria and therapeutic approaches are not well standardized. The Red Cell Working Group of the Pediatric Italian Hematogy and Oncology Association (AIEOP) developed specific recommendations to help Physicians for AIHA management. The document is available on the AIEOP website since November 1st 2013. The Italian Pediatric AIHA Group began an observational, retrospective and prospective study in order to monitor the management of children with AIHA diagnosed from 2010 to 2018, and to assess whether the availability of AIEOP recommendations had an impact on the clinical management of such patients in AIEOP Centers. We collected a national cohort of 159 children with AIHA from 21 AIEOP Centers; 48 patients were diagnosed before November 2013 and 111 patients after that date. Gender was 56% males and 44% females; median age at diagnosis was 47 months, with 11.9% under 12 months of age; 8.2% of children were born prematurely and 3.9% showed congenital malformations. 23.2 % of patients had a familiar history of immunological, hematological or oncological diseases. The median hemoglobin level at diagnosis was 6.1 gr/dL. Table 1 reports the distribution of our cases, according to the different type of autoantibodies. The comparison between the retrospective and prospective study did not reveal significative differences in clinical and biological presentation. The cold IgM forms were mainly post infective (38.4%) or primary forms (53.8%), only one patient had a secondary form due to a primitive immunodeficiency. These patients did not develop other diseases during follow up (median follow up: 28,6 months). The preliminary results of treatment and follow up of the 146 patients with warm antibody AIHA revealed the following: The treatment with conventional dose of steroids (median dose 2 mg/Kg, range 0.7- 3.5 mg/Kg) was started in 94.4% of patients, in 53% of cases on the same day of diagnosis. A high number of children used additional treatment: red blood cell transfusions (51.4%), high dose Prednisolone (59.7%), high dose i.v. Immunoglobulin (49.7%) and Plasma Exchange (1.4%). 9.5% of patients, with poor responsive disease, needed alternative drugs during the first four weeks of therapy. Response criteria were so defined: a complete response was defined as the achievement of an Hb concentration greater than or equal to the lower normal limit for age with no signs of haemolysis, i.e. normal reticulocyte count and bilirubine concentration. A partial response was defined as an increase of Hb >2 g/dL without the Hb concentration reaching a normal value for the patient age and no response as an increase of Hb< 2 g/dL and/or dependence on transfusion. A complete response was reached by 62.5%, 79.3%, 85.1% at 3, 4, 6 weeks respectively. 14.9% of patients had either a partial response or a resistant disease at 6 weeks. IgG/IgG+C3d positivity was a negative prognostic factor, as compared to positivity to C3d only, with the need of a second line treatment (prevalently Mabthera or Mycophenolate Mofetil) in 31.7% vs 0, respectively (p 0.009). Currently 6.1% of the patients were lost to follow up, 1.3% died, 55,8% are in Complete Response without events and 21.9% of the patients are still on treatment . At the last follow up, in the whole "cohort" of warm AIHA, 58% have a Primary form, 15.7% an isolated post infective form and 27.7% a Secondary form (56% Evans Syndrome). The management of the patients diagnosed after November 2013 was mostly in agreement with our recommendations, whose comprehensive therapeutic algorithm is reported in table 2, with prolonged steroid tapering in order to extend the treatment for at least 6 months. The most important difference between the retrospective and prospective study was the duration of first line treatment: 6 months or more, for steroid dependence, in 71.6% of patients in the prospective study versus 52.3% of the retrospective (p 0.031) and, more importantly, the percentage of relapsed patients: 8.3% in the prospective study versus 29.8% of the retrospective (p 0.001), these data need a longer follow up (median follow up: 24 months in the prospective study versus 63 in the retrospective) Disclosures Colombatti: Global Blood Therapeutics: Consultancy; Novartis: Consultancy; AddMedica: Consultancy.

Long Term Follow-up of Hematopoietic Stem Cell Transplantation (HSCT) for Primary Plasma Cell Leukemia (pPCL): Final Results of a Prospective Study of IFM Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4612-4612 ◽  
Author(s):  
Bruno Royer ◽  
Momar Diouf ◽  
Murielle Roussel ◽  
Lionel Karlin ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Prospective Study ◽  
Proteasome Inhibitor ◽  
Chronic Gvhd ◽  
Prospective Trial ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Long Term Follow Up ◽  
A Prospective Study

Abstract Introduction: pPCLis a rare form of multiple myeloma (MM) with very poor outcome. Current strategies including novel agents and transplantation (auto or allo-HSCT) may improve survival but the prognosis remains poor. The IFM recently published results from a prospective study incorporating tandem auto/allo-HSCT or auto/auto and maintenance after alternate induction (doxorubicin-bortezomib-cyclophosphamide and dexamethasone: PAD/VCD) in 40 pPCL patients. We report here outcomes of patients who effectively underwent second transplant (auto or allo) with long-term follow-up. Methods: 24 over 40 patients actually received second transplant:allo-HSCT (as per protocol) forpatients< 60 years-old with a donor, second auto-HSCT for others. At time of second transplant, response rates were: sCR (n=1), CR (n=8), VGPR (n=10), PR (n=5) (cf table). 7 patients received high-dose melphalan (HDM)/auto-HSCT followed by maintenance consisting in Bortezomib-Lenalidomide-Dex (VRD) every 3 months and Lenalidomideduring other months for 1 year. 17 others patients underwent allo-HSCT: syngenic(n=1) or reduced intensity conditioning (RIC)-Allo (n=16). The conditioning regimens for allo were: fludarabin-busulfan-antithymoglobulin(n=13), fludarabin-melphalan(n=1), bortezomib-fludarabin-melphalan(n=2) and HDM for syngenic(n=1). They were grafted with peripheral blood stem cells except 1 who received bone marrow and 1 cord blood unit, from related (n=9) or HLA-matched unrelated donors (n=8): median infused CD34 cells was 6.8 106/kg [3-8.5]; all pts receivedciclosporine+/-methotrexate as GvHD prophylaxis. Results: As of June 2016, median follow-up from diagnosis was44.7months[41.0;57.6], 10 patientswerestillalive.MedianPFS for allo and auto ptswas18.5months[17.8;-] and 50.1months[25.6;-]respectively ;medianOSwas39.3months[26.6;-] and notreached,respectively.Inlandmarkanalysisfromdate of second transplant, PFSwas12.2 months [8.1 ;-] for allo pts and 40.0months[17.7;-] for auto pts (p=0.085); OSwas30.0months[28.6;-] and notreached,respectively(p=0.026). 2 allo ptsdiedbefored100evaluation ; 18 patients (75%)werein VGPR orbetter : sCR=2, RC=8, VGPR=8 ; 4 patients (17%)werein PR. For allo-HSCT : 6patients developed acute GvHD which responded to steroid in 5 cases and 1 was steroid-resistant and responded secondary to anti-IL2Rα antibody;5 patients experienced chronic GVHD (mild [n=4], extensive [n=1]).3 patients received 3 months after allo as immunomodulation, donor lymphocyte infusions plusLenalidomide-Cyclophosphamide-Fludarabin(n=1), Bortezomib (n=1) and Lenalidomide (n=1): one patient in PR achieved CR and the two others in VGPR maintained their response.Day 100 treatment-related mortality was 12%: 2 patients had Epstein-Barr virus reactivation, with 1 experiencing neuromeningeal relapse of pPCL and 1 concomitant disseminated toxoplasmosis. For auto-HSCT: as per protocol, 6 received a second HDM/auto, and 1 declined. Consolidation with VRD/Len was initiated in these 7 patients: 4 receiving the planned 1 year of treatment and 3 discontinuing after 4, 8, and 10 months as a result of prolonged cytopenia. Conclusion: This is the first large prospective trial for pPCL patients including tandem auto/auto-HSCT or tandem auto/RIC-allo after induction including proteasome inhibitor. This approach is feasible, and induces high response rate but relapses remain frequent especially after RIC-allo. Tandem auto/auto plus maintenance may be superior to tandem auto/alloregarding PFS and OS. In a future trial, we will investigate tandem auto/auto after induction incorporating novel proteasome inhibitor, anti-CD38 monoclonal antibody and Lenalidomide, and followed by consolidation and prolonged maintenance. Table: characteristics of Patients Table: characteristics of Patients Figure PFS / OS Figure. PFS / OS Disclosures Roussel: amgen: Consultancy; Janssen: Consultancy; celgene: Consultancy. Karlin:janssen-cilag: Consultancy, Honoraria; amgen: Consultancy, Honoraria; celgene: Consultancy, Honoraria; Bristol: Consultancy; takeda: Consultancy. Hulin:Janssen: Honoraria; Bristol: Honoraria; Amgen: Honoraria; takeda: Honoraria; celgene: Honoraria. Macro:sanofi: Consultancy; Novartis: Honoraria; Bristol: Consultancy; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgen: Consultancy, Honoraria. Belhadj:janssen: Consultancy; novartis: Consultancy. Chaleteix:Amgen: Honoraria; Janssen: Honoraria. Leleu:TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Garderet:Takeda: Consultancy; Amgen: Consultancy; BMS: Consultancy, Honoraria; Novartis: Consultancy. Choquet:Janssen: Consultancy; Celgene: Consultancy. Fornecker:Roche: Consultancy; Takeda: Consultancy; Gilead: Consultancy; Mundipharma: Speakers Bureau. Facon:Novartis: Consultancy; Amgen: Consultancy, Speakers Bureau; Millenium/Takeda: Consultancy; Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Bristol: Consultancy; Karyopharm: Consultancy. Moreau:Bristol-Myers Squibb: Honoraria; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Celgene: Honoraria.

Bortezomib-Based Induction Therapy Followed by High-Dose Chemotherapy and Autologous Stem Cell transplantation in Newly-Diagnosed Myeloma: Initial Report From a Chinese Multiple-Center Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4557-4557
Author(s):  
Jiong Hu ◽  
Zhi-Xiang Shen
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Prospective Study ◽  
Autologous Stem Cell Transplantation ◽  
Chinese Population ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Line Treatment ◽  
Newly Diagnosed

Abstract Abstract 4557 Bortezomib-based induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is considered as standard treatment for patients with newly-diagnosed myeloma. Though front-line treatment of Bortezomib containing regimen is widely used in China, first-line treatment of high-dose chemotherapy with ASCT is not widely accepted for Chinese patients. There is also no prospective study in Chinese population to evaluate the efficacy, safety and feasibility of such treatment strategy. This is a prospective study in young Chinese population (18–65 year old) with newly-diagnosed myeloma (NCT00984828). All patients will receive 4 cycles of Bortezomib and Dexamethasone as frontline therapy. After that, patients will receive either a single ASCT conditioning with melphalan 200mg/m2 (mel 200) or ASCT with mel 200 + bortezomib conditioning and another 3 cycles of Bortezomib monotherapy as consolidation after ASCT. From Jan 2010, a total of 37 patients (median age 54, 31∼64) were enrolled in this study. There were 2 patients died of treatment toxicity 1 and 3 months after entering study. In the remaining 35 patients, 17 already finished ASCT and other 18 patients declined the ASCT. In 23 evaluable patients, 11 achieved CR (n=10) and VGPR (n=1), 9 with PR, 2 with SD and 1 PD. At the last follow-up at May 2012, a total of 6 patients experienced disease progression and no patients died of disease or treatment associated toxicity. As a whole group, with a median follow-up of 10 months (1∼33 months), the estimated 2-year OS and PFS were 94.3±4% and 66.2±12.3% respectively. Though further analysis was impossible with limited number of patient enrolled in the study with short follow-up, overall, the treatment was safe particularly no significant treatment associated toxicity or treatment mortality documented during and after ASCT procedure. The overall 43% CR rate was comparable to most previous reports. The early analysis of the study demonstrated that Bortezomib-Dexa followed by ASCT can be safely performed in Chinese population and further enrolled and follow-up may provide evidence of long-term efficacy of such strategy in Chinese population. Disclosures: No relevant conflicts of interest to declare.

First Large Prospective Study For Patients With Primary Plasma Cell Leukemia: Bortezomib-Doxorubicine-Dexamethasone/Bortezomib-Cyclophosphamide-Dexamethasone Regimens As Induction Before Stem Cell Transplantation Followed By Consolidation With Lenalidomide-Bortezomib-Dex Or Allograft. (a study of the IFM group)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 761-761
Author(s):  
Bruno Royer ◽  
Florence Magrangeas ◽  
Bruno Lioure ◽  
Jean-Paul Fermand ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Prospective Study ◽  
Cell Transplantation ◽  
Plasma Cell ◽  
Plasma Cells ◽  
High Dose ◽  
Cell Leukemia ◽  
Primary Plasma Cell Leukemia

Abstract Introduction Primary plasma cell leukemia (pPCL) is a rare form of plasma cell malignancy with poor prognosis (usually less than 12 months survival with conventional chemotherapy). Only one prospective study with Lenalidomide-Dex before high dose therapy has been recently reported1. Bortezomib-based regimens and high dose Melphalan/ autologous stem cell transplantation (HDM/ASCT) have shown promising results in small retrospective studies. We report here the first prospective multicenter phase II trial for pPCL patients (pts) treated with Bortezomib-Doxorubicine-Dexamethasone (PAD) / Bortezomib-Cyclosphosphamide-Dexamethasone (VCD) as induction before HDM/ASCT. With the aim to improve response and survival, allograft or second ASCT plus consolidation/maintenance with Lenalidomide-Bortezomib-Dex (VRD) were proposed. Patients and method Non-previously treated pts with a diagnosis of pPCL were enrolled in this phase II study of the IFM group from April 2010 to July 2013. PAD (dexa 40 mg + bortezomib 1,3 mg/m2 on day 1, 4, 8, 11 + doxorubicine 30 mg/m2 day 4) and VCD (dexa + bortezomib + cyclophosphamide 300 mg/m2 day 1, 8) were administrated alternatively each 21 days for 4 cycles. For responding patients with circulating plasma cell < 1%, peripheral stem cells were collected after Cyclophosphamide + G-CSF. Either (i) double HDM/ASCT was performed followed by consolidation/maintenance íVDR (dexa 40mg + bortezomib 1,3 mg/m2 on day 1, 4, 8, 11 + lenalidomide 15 mg day 1-15) each 3 months and Lenalidomide 15 mg 21/28 days on others months, for 1 yearý or (ii) tandem HDM/ASCT-reduced intensity conditioning-allograft if there were < 66 years-old. Primary end-point was progression free survival (PFS); secondary end-points were responses rates, overall survival (OS), feasibility, and toxicity. We evaluated the disease response to therapy with the IMWG criteria and the percentage of circulating plasma cells; minimal residual disease (MRD) was evaluated during follow-up. Peripheral circulating plasma cells and bone marrow plasmocytes were collected at diagnosis for centralized FISH and SNP array analysis. Results 40 pts were enrolled with a median age of 55y (27-71). Median follow-up was 12.6 months (7.6-24.8). At diagnosis, the median number of circulating plasma cell was 5.2 G/L (1.3-66). Twenty-two percent had creatinine clearance < 50 ml/min, and 11% < 30 ml/min, 44% had an ISS score of 2 and 37% ISS 3. After induction 35 pts are evaluable. In the intent to treat analysis, 25 (72%) responded (VGPR+CR 37%, PR 28%, SD 5%) and 10/35 (28%) were refractory (pts having circulating plasma cell ≥ 1%) and did not continue the study. Twenty-three of the 25 responding pts underwent HDM/auto and 20 pts are evaluable at 3 months: CR+VGPR 14/20 (70%), PR 4/20 (20%), 1/20 (5%) and PD 1/20 (5%). Second HDM/auto was performed in 6 pts and allograft in 12. Ten of the 14 (72%) evaluable pts achieved VGPR or better and 4/14 (28%) PR. Six pts are currently on consolidation/maintenance phase with VRD. Median PFS was 17.8 months. Median OS was not reached. Genomic data are shown in Table I. MDR evaluation will be presented later. Major toxicities were hematological and infections. Eight pts died: 5 during induction, 1 at HDM/ASCT and 2 post allograft while in relapse. Of note, 2 pts had meningeal involvement at relapse. Conclusion This first large study for pPCL patients with PAD/VCD as induction and HDM/ASCT is effective and induce high responses rates. Consolidation with Allograft or bortezomib-lenalidomide-dex is currently investigated. 1Musto P et al. Blood (ASH Annual Meeting Abstracts) 2011; 118 Abstract2925Table I: genomic Disclosures: Leleu: CELGENE: Honoraria; JANSSEN: Honoraria. Moreau:Celgene: Honoraria, Speakers Bureau. Avet-Loiseau:CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau.

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