Study of the Outcome of Pediatric Patients with Aplastic Anemia treated with Immunosuppressive Therapy at Ain Shams University Pediatric Hospital

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
W Mohamed ◽  
S Matboly ◽  
N Morcy
Keyword(s):  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Alternative Therapy ◽  
Patient Characteristics ◽  
Complete Response ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Pediatric Age Group ◽  
Best Response ◽  
Life Threatening

Abstract Background Aplastic anemia (AA) is life threatening disorder in pediatric age group with an increasing incidence nowadays. Hematopoietic stem cell transplant being the 1st line therapy; immunosuppressive therapy (IST) is the alternative therapy and is the most commonly used modality of treatment especially in the developing countries. Aim of the Work to assess the outcome of IST in children with severe and very severe AA. Patients and Methods Data for 23 children treated with IST from January 201 0 to January 201 9 (10 years) were retrieved from clinic records. IST included rabbit anti thymocyte globulin (ATG) along with cyclosporine A and another group were treated by sandimmune alone. Results Patient characteristics included median age (9) with 73.9% male and 26.1% female. With median interval between diagnosis and start of IST 2(1 -5) months and around 30.4% with hepatitis A associated aplastic anemia. Complete response, and no response were seen in 4 (50%) patients and 4(50%) patients, respectively in patients received ATG and sandimune. While in patients received sandimune alone complete response, partial response and no response were seen in 7(46.7%) patients, 5 (33.3%) patients, and 3 (20%) patients respectively. The median time to best response in the whole cohort was 2 months. There was no difference in outcome related to severity of AA, or higher Hb or platelet level. There was a significantly better rate of response in both groups of patients with higher initial TLC count (p = 0.001) initial ANC (p = 0.002), initial ALC (p = 0.001), and initial ARC (p = 0.014) before start of IST. An overall response rate in both groups around of 43.47% reported a 5-year OS. With 45.5 of patients with complete response had HAAA. A delayed time to complete response with prolonged requirement of cyclosporine therapy was detected in the study. Conclusion In a developing country setting, IST with ATG and cyclosporine seems to be an alternative treatment for children with aplastic anemia lacking MRD.

Study of the Outcome of Pediatric Patients with Aplastic Anemia treated with Immunosuppressive Therapy at Ain Shams University Pediatric Hospital

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
W Mohamed ◽  
S Matboly ◽  
N Morcy
Keyword(s):  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Alternative Therapy ◽  
Patient Characteristics ◽  
Complete Response ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Pediatric Age Group ◽  
Best Response ◽  
Life Threatening

Abstract Background Aplastic anemia (AA) is life threatening disorder in pediatric age group with an increasing incidence nowadays. Hematopoietic stem cell transplant being the 1st line therapy; immunosuppressive therapy (IST) is the alternative therapy and is the most commonly used modality of treatment especially in the developing countries. Aim of the Work to assess the outcome of IST in children with severe and very severe AA. Patients and Methods Data for 23 children treated with IST from January 201 0 to January 201 9 (10 years) were retrieved from clinic records. IST included rabbit anti thymocyte globulin (ATG) along with cyclosporine A and another group were treated by sandimmune alone. Results Patient characteristics included median age (9) with 73.9% male and 26.1% female. With median interval between diagnosis and start of IST 2(1 -5) months and around 30.4% with hepatitis A associated aplastic anemia. Complete response, and no response were seen in 4 (50%) patients and 4(50%) patients, respectively in patients received ATG and sandimune. While in patients received sandimune alone complete response, partial response and no response were seen in 7(46.7%) patients, 5 (33.3%) patients, and 3 (20%) patients respectively. The median time to best response in the whole cohort was 2 months. There was no difference in outcome related to severity of AA, or higher Hb or platelet level. There was a significantly better rate of response in both groups of patients with higher initial TLC count (p = 0.001) initial ANC (p = 0.002), initial ALC (p = 0.001), and initial ARC (p = 0.014) before start of IST. An overall response rate in both groups around of 43.47% reported a 5-year OS. With 45.5 of patients with complete response had HAAA. A delayed time to complete response with prolonged requirement of cyclosporine therapy was detected in the study. Conclusion In a developing country setting, IST with ATG and cyclosporine seems to be an alternative treatment for children with aplastic anemia lacking MRD.

Relapse of Children with Aplastic Anemia after Immunosuppressive Therapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3098-3098
Author(s):  
Takuya Kamio ◽  
Etsuro Ito ◽  
Akira Ohara ◽  
Yoshiyuki Kosaka ◽  
Masahiro Tsuchida ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Family Member ◽  
Immunosuppressive Therapy ◽  
Severe Disease ◽  
Cord Blood Transplantation ◽  
Complete Response ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Second Line ◽  
Hematopoietic Stem

Abstract Although the therapeutic outcome for acquired aplastic anemia (AA) has improved markedly with the introduction of immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A (CyA), a significant portion of patients treated with IST subsequently relapse and require second-line therapy. However, detailed analysis of the relapse cases has not been reported. In this study, we assessed the relapse rate, response to second-line treatment after relapse and prognosis. From November 1992 to July 2007, 473 newly diagnosed AA children (213 female, 260 male) entered two consecutive prospective studies (AA-92 and AA-97). The median age was 8 years, ranging from 1 to 18 years. Patients with very severe (n = 210), severe (n = 149) and non-severe disease (n = 114) received initial IST consisting of ATG and/or CyA. At six months after the initial IST, 280 patients (59.2%) achieved CR (n = 94) or PR (n=186). Relapse is defined by conversion to no response (NR) from partial or complete response (PR/CR). Among the 280 patients who responded to IST, 49 (17.5%) relapsed. The cumulative incidence of relapse was 19.6% at 10 years and the median time to relapse was 18 months, ranging 7 to 138 months. Among the 49 patients who relapsed, 22 received a second round of IST with ATG and CyA. Fourteen patients (63.6%) responded to the second round. However, three relapsed, and two developed paroxysmal nocturnal hemoglobinuria. Eight patients received CyA after relapse. Four patients responded to CyA, but two relapsed subsequently. Hematopoietic stem cell transplantation (HSCT) was attempted in 26 patients who relapsed after initial responses. Before HSCT, nine received a second course of IST with ATG and CyA and two received CyA. Fifteen patients progressed directly to HSCT. Bone marrow transplantation (BMT) from an HLA-matched sibling (n =7), HLA-matched family member (n = 1), or HLA-mismatched family member (n = 2) was performed in 10 patients, and all are presently alive. BMT from an unrelated donor was attempted in 13 patients, and four died of complications related to BMT. Cord blood transplantation from an unrelated donor was attempted in two patients and two patients are alive. Of the 26 patients who received HSCT, 21 are alive and well, 22 to 137 months (median 72 months) following transplantation. There were seven deaths out of total 49 who initially relapsed. The causes of death were HSCT-related complications (n = 5), MDS/acute myelogenous leukemia (n = 1), bacteremia (n = 1). Eight of 9 patients who received HSCT following a second round of IST are alive and well. The present study suggests that a second round of IST should be offered to the patients who relapse, and HSCT should be considered for the patients who fail to respond to the second round of IST.

scholarly journals Pharmacokinetics and Safety of Intravenous Cidofovir for Life-Threatening Viral Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients

2015 ◽  
Vol 59 (7) ◽  
pp. 3718-3725 ◽  
Author(s):  
Amy E. Caruso Brown ◽  
Mindy N. Cohen ◽  
Suhong Tong ◽  
Rebecca S. Braverman ◽  
James F. Rooney ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Half Life ◽  
Viral Infections ◽  
Multiorgan Failure ◽  
Kidney Injury ◽  
Cell Transplant ◽  
Open Label ◽  
Hematopoietic Stem ◽  
Life Threatening

ABSTRACTChildren undergoing hematopoietic stem cell transplantation (HSCT) are at risk for life-threatening viral infections. Cidofovir is often used as a first-line agent for adenovirus infections, despite the absence of randomized controlled trials with HSCT patients, and as a second-line agent for resistant herpesvirus infections. The frequency and severity of adverse effects, particularly nephrotoxicity, in pediatric HSCT recipients are unclear, and pharmacokinetics (PK) of cidofovir in children have not previously been reported. This study was an open-label, nonrandomized, single-dose pilot study to determine the safety and PK of cidofovir in pediatric HSCT recipients with symptomatic adenovirus, nucleoside-resistant cytomegalovirus (CMV) or herpes simplex virus (HSV), and/or human papovavirus infections. Subsequent dosing and frequency were determined by clinical response and side effects, as assessed by the treating physician. Blood and urine samples were obtained from patients for PK studies and assessment of toxicity and virologic response. Twelve patients were enrolled (median age, 9 years; 33.5 days posttransplantation). Four of seven patients with adenovirus infection were successfully treated and eventually cleared their infections. Four of twelve patients died of disseminated viral disease and multiorgan failure. Two of twelve patients had evidence of acute kidney injury after the first dose, and one of these patients developed chronic kidney disease; two other patients developed late nephrotoxicity. The mean drug half-life was 9.5 h. There was no correlation between nephrotoxicity and plasma maximum concentration, clearance, or half-life. PK were similar to those reported for adults, although the drug half-life was significantly longer than that for adults. Cidofovir was well tolerated in the majority of patients. However, effective therapeutic strategies are urgently needed to support patients until immune reconstitution is achieved.

scholarly journals Prognostic Significance of Tumor Response at the End of Therapy in Group III Rhabdomyosarcoma: A Report From the Children's Oncology Group

2009 ◽  
Vol 27 (22) ◽  
pp. 3705-3711 ◽  
Author(s):  
David A. Rodeberg ◽  
Julie A. Stoner ◽  
Andrea Hayes-Jordan ◽  
Simon C. Kao ◽  
Suzanne L. Wolden ◽  
...  
Keyword(s):  
Alternative Therapy ◽  
Prognostic Significance ◽  
Complete Response ◽  
Disease Recurrence ◽  
Radiographic Measurement ◽  
Clinical Group ◽  
Group Iii ◽  
Best Response ◽  
Pathology Reports ◽  
The Impact

Purpose Some patients with rhabdomyosarcoma (RMS) achieve less than a complete response (CR) despite receiving all planned therapy. We assessed the impact of best response at the completion of all therapy on patient outcome. Patients and Methods We studied 419 clinical group III participants who completed all protocol therapy without developing progressive disease for Intergroup Rhabdomyosarcoma Study (IRS) IV. Response (complete resolution [CR], partial response [PR; ≥ 50% decrease], or no response [NR; < 50% decrease and < 25% increase]) was determined by radiographic measurement and categorized by the best response. Results At the end of therapy, 341 participants (81%) achieved a best response of CR and 78 (19%) had a best response of PR/NR. Five-year failure-free survival was similar for participants achieving CR (80%) and PR/NR (78%). After adjustment for age, nodal status, primary site, and histology, there was no significant indication of lower risk of failure (hazard ratio [HR], 0.77; 95% CI, 0.46 to 1.27; P = .3) nor death (HR, 0.63; 95% CI, 0.36 to 1.09; P = .1) for CR versus PR/NR participants. Seventeen participants with a best response of PR/NR had surgical procedures; eight (50%) of 16 with available pathology reports had residual viable tumor and only three achieved a complete resection. Resection of residual masses was not associated with improved outcome. Conclusion CR status at the end of protocol therapy in clinical group III participants was not associated with a reduction of disease recurrence and death. Aggressive alternative therapy may not be warranted for RMS patients with a residual mass at the end of planned therapy.

scholarly journals Human Adenovirus 7-Associated Hemophagocytic Lymphohistiocytosis-like Illness: Clinical and Virological Characteristics in a Cluster of Five Pediatric Cases

2020 ◽  
Author(s):  
William R Otto ◽  
Edward M Behrens ◽  
David T Teachey ◽  
Daryl M Lamson ◽  
David M Barrett ◽  
...  
Keyword(s):  
Genetic Predisposition ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Definitive Treatment ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Threatening Condition ◽  
Epidemiology Data ◽  
Life Threatening

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation. Children often suffer from primary genetic forms of HLH, which can be triggered by infection. Others suffer from secondary HLH as a complication of infection, malignancy, or rheumatologic disease. Identifying the exact cause of HLH is crucial, as definitive treatment for primary disease is hematopoietic stem cell transplant. Adenoviruses have been associated with HLH but molecular epidemiology data are lacking. Methods We describe the clinical and virologic characteristics of 5 children admitted with adenovirus infection during 2018–2019 who developed HLH or HLH-like illness. Detailed virologic studies, including virus isolation and comprehensive molecular typing were performed. Results All patients recovered; clinical management varied but included immunomodulating and antiviral therapies. A genetic predisposition for HLH was not identified in any patient. Adenovirus isolates were recovered from 4/5 cases; all were identified as genomic variant 7d. Adenovirus type 7 DNA was detected in the fifth case. Phylogenetic analysis of genome sequences identified 2 clusters—1 related to strains implicated in 2016–2017 outbreaks in Pennsylvania and New Jersey, the other related to a 2009 Chinese strain. Conclusions It can be challenging to determine whether HLH is the result of an infectious pathogen alone or genetic predisposition triggered by an infection. We describe 5 children from the same center presenting with an HLH-like illness after onset of adenovirus type 7 infection. None of the patients were found to have a genetic predisposition to HLH. These findings suggest that adenovirus 7 infection alone can result in HLH.

Multi-Agent Phase I Trials in Childhood Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4528-4528
Author(s):  
Richard Sposto ◽  
Elizabeth A. Raetz ◽  
Charles P. Reynolds ◽  
Paul S. Gaynon
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Cell Transplant ◽  
Phase I Trials ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Background: Single agent phase I trials with conventional methodology may not be suitable for children with relapsed leukemia. Accrual of children with ALL in relapse to single-agent phase I trials is poor due to clinical urgency and a &gt; 30% likelihood of complete response (CR) with a variety conventional agents combinations (Br J Haematol.2005; 131(5): 579) with the option of hematopoietic stem cell transplant in remission. As most drugs are ultimately used in combination, a Phase I trial testing a new agent in combination with conventional agents would seem most useful and might increase accrual. However, with conventional phase I methodologies determination of a maximum tolerated dose is complicated by the toxicities of the accompanying conventional agents and by the background morbidity of relapsed leukemia. Methods: The Children’s Oncology Group (COG) study, AALL01P2, employed vincristine, prednisone, doxorubicin, and pegylated asparaginase for children with ALL in first marrow relapse. We determined the incidence of conventional non-hematologic dose limiting toxicities (DLT’s) and modeled the impact on a hypothetical phase I trial of a candidate agent with no additional toxicity. Results: Among 111 patients on AALL01P2, 19% had conventional non-hematologic DLT’s. Induction therapy was judged clinically acceptable. With a traditional Phase I escalation scheme that accepts 0/3 and 1/6 DLT’s at a dose-level and rejects 2/3 and 2/6 DLT’s, an agent that adds no morbidity would be rejected as too toxic at any dose 30% of the time. Conclusion: Background morbidity confounds identification of an acceptable dose of a non-toxic new agent tested in combination with conventional drugs for recurrent ALL. We propose a modification to the traditional Phase I design that increases the DLT thresholds to 1/3 and 2/6, which effectively compensates for background toxicity and reduces the chance of falsely rejecting an acceptable agent.

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