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1.
Bull Cancer ; 110(2S): S1-S12, 2023 Feb.
Article in French | MEDLINE | ID: mdl-36244825

ABSTRACT

Inherited Metabolic Diseases (IMD) are rare genetic diseases, including both lysosomal and peroxisomal diseases. Lysosomal diseases are related to the deficiency of one or more lysosomal enzymes or transporter. Lysosomal diseases are progressive and involve several tissues with most often neurological damage. Among peroxisomal diseases, X-linked adrenoleukodystrophy (ALD) is a neurodegenerative disease combining neurological and adrenal damage. For these diseases, enzyme replacement therapy (ERT), allogeneic hematopoietic cell transplantation (allo-HCT) and gene therapy represent various possible treatment options, used alone or in combination. The purpose of this workshop is to describe the indications, modalities, and follow-up of allo-HCT as well as the use of ERT peri-transplant. All indications for transplant in these rare diseases are associated with comorbidities and are subject to criteria that must be discussed in a dedicated national multidisciplinary consultation meeting. There are some consensual indications in type I-H mucopolysaccharidosis (MPS-IH) and in the cerebral form of ALD. For other IMDs, no clear benefit from the transplant has been demonstrated. The ideal donor is a non-heterozygous HLA-identical sibling. The recommended conditioning is myeloablative combining fludarabine and busulfan. In MPS-IH, ERT has to be started at diagnosis and continued until complete chimerism and normal enzyme assay are achieved. The pre-transplant assessment and post-transplant follow-up are made according to the published recommendations (PNDS). Standard follow-up is carried out jointly by the transplant and referral teams.


Subject(s)
Hematopoietic Stem Cell Transplantation , Mucopolysaccharidoses , Neurodegenerative Diseases , Humans , Mucopolysaccharidoses/therapy , Transplantation, Homologous , Busulfan , Transplantation Conditioning
2.
Bull Cancer ; 108(12S): S1-S9, 2021 Dec.
Article in French | MEDLINE | ID: mdl-34176584

ABSTRACT

Allogeneic hematopoietic cell transplantation (allo-HCT), the only curative therapy for numerous hematological malignancies, carries a significant risk of morbidity and mortality. The patients and families' expectations regarding the procedure, the prognosis uncertainties, as well as the existence of potential new therapeutic possibilities, lead to frequent use of intensive care. Even though the transplant physicians are highly skilled in acute care, their knowledge of palliative approach is limited, making the use of palliative care insufficient and often late. By promoting reflection on the proportionality of care and the patients' quality of life, palliative care may contribute to the allo-HCT patients management. Nevertheless, obstacles to this approach remain. The objective of this work is to propose recommendations to promote the implementation of palliative care into transplant units.


Subject(s)
Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Palliative Care , Advance Directives , Allografts , Attitude of Health Personnel , Bacterial Proteins , Child , Clinical Decision-Making , Clinical Deterioration , Glucosyltransferases , Health Care Surveys/methods , Health Care Surveys/statistics & numerical data , Hematopoietic Stem Cell Transplantation/psychology , Humans , Interdisciplinary Communication , Interprofessional Relations , Palliative Care/organization & administration , Palliative Care/psychology , Prognosis , Qualitative Research , Quality of Life , Societies, Medical , Terminal Care
3.
Bull Cancer ; 108(12S): S30-S38, 2021 Dec.
Article in French | MEDLINE | ID: mdl-33966887

ABSTRACT

Graft-versus-host disease (GVHD) is the most common complication after allogeneic hematopoietic cell transplantation (allo-HCT) with a frequency range of 30% to 50%. GVH is the leading cause of non-relapse-related deaths and a cause early mortality. Gastro-intestinal (GI) GVH results in digestive manifestations that involve the small intestine and the colon. The patient may then have diarrhea, intestinal bleeding, abdominal pain but also clinical signs such as nausea and vomiting may lead to anorexia. GI-GVHD promotes undernutrition as well as significant losses of vitamins and trace elements. In the case of post-transplant diarrhea, differential diagnosis can include GI-GVHD, infection and drug toxicity. Although, corticosteroids w/wo calcineurin inhibitors represent the standard of care in first line treatment, there is no consensus regarding salvage therapy in case of corticoresistant GI-GVH. In addition, assessment of early nutritional status would help combating undernutrition, which is an independent risk factor for mortality in patients with GI-GVHD. In this workshop of the Fancophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) we focused on the management of patients developing GI-GVHD following allo-HCT.


Subject(s)
Gastrointestinal Diseases , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation/adverse effects , Postoperative Complications , Adrenal Cortex Hormones/therapeutic use , Diagnosis, Differential , Diarrhea/etiology , Drug Resistance , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/therapy , Graft vs Host Disease/complications , Graft vs Host Disease/diagnosis , Graft vs Host Disease/therapy , Humans , Nutritional Status , Nutritional Support , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/therapy , Salvage Therapy
5.
Fundam Clin Pharmacol ; 35(2): 435-445, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32740936

ABSTRACT

Medication non-adherence (NA) after allogeneic hematopoietic cell transplantation (allo-HCT) can lead to serious complications. This study assesses NA in French adult and pediatric recipients and identifies factors associated with NA. In accordance with the EMERGE and STROBE guidelines, a cross sectional multicentric survey was conducted. We used a self-reported questionnaire that was adapted to adults and pediatrics and that could provide a picture of all three phases of medication adherence: initiation, implementation, persistence. We enrolled 242 patients, 203 adults (mean age: 51 years old, 50.7% male) and 39 children (mean age: 9 years old, 56.4% female). Reported NA was estimated at about 75% in both populations, adults and pediatrics. In adults, the univariate analysis showed that patients less than 50 years old (P = 0.041), (i) treated with cyclosporine (P = 0.02), (ii) treated with valacyclovir/acyclovir (P = 0.016), and (iii) experiencing side effects (P = 0.009), were significantly more non-adherent. In multivariate analysis, only recipient age was significantly associated to NA (P = 0.05). The limited size of the pediatric population did not allow us to draw any statistical conclusion about this population. To the best of our knowledge, this is the first study in France on NA in allo-HCT recipients. Our results highlight the age factor as the only factor related to NA. Further studies are needed to confirm our observations and refine results in pediatric populations, currently most at risk of medication NA.


Subject(s)
Hematopoietic Stem Cell Transplantation , Medication Adherence/statistics & numerical data , Acyclovir/therapeutic use , Algeria , Belgium , Child , Cross-Sectional Studies , Cyclosporine/therapeutic use , Female , Humans , Male , Middle Aged , Surveys and Questionnaires
6.
Cancers (Basel) ; 12(11)2020 Nov 17.
Article in English | MEDLINE | ID: mdl-33212828

ABSTRACT

Data regarding coronavirus disease 2019 (COVID-19) description are still limited in pediatric oncology. The French society of pediatric oncology (SFCE) initiated a study to better describe COVID-19 in patients followed in French pediatric oncology and hematology wards. All patients diagnosed with COVID-19 and followed in a SFCE center were enrolled. Data from medical records were analyzed for all patients enrolled up to the end of May 2020. Data were available for 37 patients. Thirty-one were children under 18 years of age. Nineteen patients were female. Seventeen patients had a solid tumor, 16 had a hematological malignancy and four recently underwent hematopoietic stem cell transplantation (HSCT) for non-oncological conditions. Twenty-eight patients presented symptoms, most often with fever, cough, rhinorrhea and asthenia. Ground-glass opacities were the most frequent radiological finding with abnormalities mostly bilateral and peripherally distributed. Twenty-four patients received chemotherapy a month prior to COVID-19 diagnosis. Most patients did not require hospitalization. Three patients required oxygen at the time of diagnosis. In total, five patients were admitted in an intensive care unit because of COVID-19 and one died from the disease. Children and young adults treated for a cancer and/or with a HSCT may be at risk for severe COVID-19 and should be closely monitored.

7.
Pediatr Blood Cancer ; 67(10): e28603, 2020 10.
Article in English | MEDLINE | ID: mdl-32706505

ABSTRACT

BACKGROUND: Busulfan (Bu) is the cornerstone of conditioning regimens prior to hematopoietic stem cell transplantation, widely used in both adults and children for the treatment of malignant and nonmalignant diseases. Despite an intravenous formulation, interindividual variability (IIV) remains high and optimal exposure difficult to achieve, especially in neonates and infants. PROCEDURE: To ensure both efficacy and safety, we set up in 2005 an observational study designed for children not fully assessed during the drug registration procedure. From a large cohort of 540 patients, we developed a Bu population pharmacokinetic model based on body weight (BW) and maturation concepts to reduce IIV and optimize exposure. A new dosing nomogram was evaluated to better fit the population pharmacokinetic model. RESULTS: Bu clearance IIV was significantly decreased from 61.3% (covariate-free model) to 28.6% when combining BW and maturation function. Median Bu area under the curve (AUC) was 1179 µmol/L × min compared to 1025 with the EMA dosing nomogram for children <9 kg. The target AUC was reached for each BW strata, significantly increasing the percentages of patients achieving reaching the targeted AUC as compared to FDA schedule. CONCLUSION: This new model made it possible to propose a novel dosing nomogram that better considered children below 16 kg of BW and allowed better initial exposure as compared to existing dosing schedules. This nomogram, which would be easy to use to determine an optimal dosing schedule in daily practice, will need to be validated in clinical routine. Therapeutic drug monitoring remains strongly advisable for small children and those with specific diseases.


Subject(s)
Busulfan/pharmacokinetics , Busulfan/therapeutic use , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Models, Statistical , Nomograms , Transplantation Conditioning , Combined Modality Therapy , Dose-Response Relationship, Drug , Drug Monitoring , Female , Follow-Up Studies , Hematologic Neoplasms/pathology , Humans , Infant , Male , Myeloablative Agonists/pharmacokinetics , Myeloablative Agonists/therapeutic use , Prognosis , Tissue Distribution
8.
Pediatr Transplant ; 24(4): e13694, 2020 06.
Article in English | MEDLINE | ID: mdl-32196861

ABSTRACT

Antithymocyte globulin is a major drug in transplantation. rATG has been successfully used to prevent graft-versus-host disease in allogeneic HSCT. However, its first infusion is associated with reactions ranging from simple fevers to distributive shocks and may interfere with the transplant conditioning. To evaluate the impact of rATG infusion rate on clinical tolerability, we conducted a retrospective study of all pediatric allogeneic HSCT patients who received rATG (Thymoglobulin®) as part of their conditioning at Lille University Hospital from 2003 to 2018. Until 2012, patients received rATG with a theoretical infusion time of 12 hours (12H group, n = 33). From 2012, they had a theoretical infusion time of 4 hours (4H group, n = 43). Patients from the 12H arm presented more ≥ grade 3 infusion-related reactions at first dose (70% versus 44%, P = .027), had significantly higher fever (median of 39.6°C versus 39.2°C, P = .002), and needed a greater use of symptomatic treatments. However, they received a slightly higher first dose of rATG (median of 2.7 versus 2.3 mg/kg, P = .042). In view of these results, a rATG infusion time of 4 hours can be a relevant option for pediatric transplant centers to avoid interference with the conditioning regimen and facilitate medical surveillance.


Subject(s)
Antilymphocyte Serum/administration & dosage , Hematopoietic Stem Cell Transplantation , Immunologic Factors/administration & dosage , Transplantation Conditioning/methods , Adolescent , Child , Child, Preschool , Female , Hematopoietic Stem Cell Transplantation/methods , Humans , Infusions, Intravenous , Male , Retrospective Studies , Time Factors , Transplantation, Homologous
9.
Bull Cancer ; 107(1S): S18-S27, 2020 Jan.
Article in French | MEDLINE | ID: mdl-30952358

ABSTRACT

Hepatobiliary complications are frequent in the context of allogeneic hematopoietic cell transplantation (allo-HCT) and contribute largely to the morbidity and mortality after transplantation. Within the framework of the ninth workshops of practice harmonization of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held in Lille in September 2018, diagnostic approaches and treatments of hepatobiliary dysfunctions prior to and following transplantation were reviewed according to the analysis of published studies.


Subject(s)
Biliary Tract Diseases/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Liver Diseases/etiology , Allografts , Biliary Tract Diseases/diagnosis , Biliary Tract Diseases/therapy , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/therapy , Disease Management , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Graft vs Host Disease/therapy , Hepatitis, Viral, Human/diagnosis , Hepatitis, Viral, Human/therapy , Hepatitis, Viral, Human/transmission , Humans , Iron Overload/diagnosis , Iron Overload/etiology , Iron Overload/therapy , Liver Diseases/diagnosis , Liver Diseases/therapy , Time Factors , Transplantation Conditioning/adverse effects
10.
Bull Cancer ; 107(1S): S28-S35, 2020 Jan.
Article in French | MEDLINE | ID: mdl-31303250

ABSTRACT

Acute and chronic renal failures are very common after allogeneic HSCT. These complications have a real impact on mortality and morbidity of transplant recipients. Within the framework of the ninth workshops of practice harmonization of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held in Lille in September 2018, various causes and mechanisms of renal failure, diagnostic work-up, treatment and recommendations to limit renal failure after transplantation are reviewed. Recommendations to adjust medications to avoid renal failure are also proposed in this article.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Renal Insufficiency/etiology , Renal Insufficiency/prevention & control , Anti-Infective Agents/adverse effects , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Graft vs Host Disease/therapy , Humans , Immunosuppressive Agents/adverse effects , Incidence , Nephrotic Syndrome/etiology , Renal Insufficiency/diagnosis , Renal Insufficiency/therapy , Severity of Illness Index , Thrombotic Microangiopathies , Transplantation Conditioning/adverse effects , Transplantation, Homologous
11.
Bull Cancer ; 106(1S): S1-S9, 2019 Jan.
Article in French | MEDLINE | ID: mdl-30580913

ABSTRACT

Allogeneic hematopoietic cell transplantation (HCT) is part of the standard of care for many hematological diseases. Over the last decades, significant advances in patient and donor selection, conditioning regimens as well as supportive care of patients undergoing allogeneic HCT leading to improved overall survival have been made. In view of many new treatment options in cellular and molecular targeted therapies, the place of allogeneic transplantation in therapy concepts must be reviewed. Most aspects of HCT are well standardized by national guidelines or laws as well as by certification labels such as FACT-JACIE. However, the requirements for human resources, construction and layout of a unit treating patients during the transplantation procedure and for different complications are not well defined. Here, we describe the process of planning a transplant unit in order to open a discussion that could lead to more precise guidelines in the field of personnel and infrastructural requirements for hospitals caring for people with severe immunosuppression.


Subject(s)
Bone Marrow Transplantation/standards , Health Facility Environment/standards , Hematologic Diseases/therapy , Hematopoietic Stem Cell Transplantation/standards , Air/standards , Cell- and Tissue-Based Therapy/standards , Diet, Healthy/standards , Donor Selection/standards , France , Health Personnel/standards , Hospital Units/standards , Humans , Hygiene , Immunosuppression Therapy/standards , Monitoring, Physiologic/methods , Protective Clothing/standards , Societies, Medical , Sterilization/standards , Transplantation, Homologous/standards , Visitors to Patients
12.
Bull Cancer ; 104(12S): S136-S141, 2017 Dec.
Article in French | MEDLINE | ID: mdl-29169651

ABSTRACT

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th allogeneic hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2016 in Lille, France. The objective of our workshop is to provide a discussion on the conservation and congelation of hematopoietic stem cells in a pediatric setting as well as our recommendations for this technique.


Subject(s)
Cryopreservation/standards , Hematopoietic Stem Cells , Autografts , Child , France , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/standards , Humans , Societies, Medical , Tissue and Organ Procurement/organization & administration , Tissue and Organ Procurement/standards
13.
Childs Nerv Syst ; 33(12): 2181-2186, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28762040

ABSTRACT

PURPOSE: Osteopetrosis (OP) is a rare skeletal disease, which can affect the skull base and calvaria. A multidisciplinary approach is mandatory and patient may need neurosurgical care. Few observations have been published, and optimal management of OP is not established yet. METHOD: We report a case of an infant with OP diagnosed at 5 months, who presented signs of intracranial hypertension associated with unilateral blindness. Bone marrow allograft was performed at 6 months of age. At neurosurgical first examination at 11 months, the child was hypotonic, with severe amblyopia; features of bicoronal synostosis were appreciated, with tense anterior fontanel bulging indicating synostotic oxycephaly. Head circumference had decreased from +3 SD to +1SD. Cerebral CT scan showed reduction of intracranial volume, inward thickening of the calvaria, bilateral stenosis of optic canal, ventricular dilatation, enlarged arachnoid spaces, and tonsillar herniation. We performed cranial vault expansion with frontal advancement and bi parietal decompression, thinning of the inner table, unroofing of the left orbit and optic canal in order to obtain optic nerve decompression. RESULTS: Postoperative course was uneventful, and the patient was discharged on day 8. Vision was unchanged but rapid improvement of axial tonus was noted. The CT scan showed satisfactory calvarial expansion with regression of tonsillar herniation. CONCLUSIONS: Neurosurgical evaluation and care are necessary in the context of a multidisciplinary approach to the patient affected by osteopetrosis. Cranial vault remodeling and expansion should be considered in patients with sign of intracranial hypertension. Timing of optic canal decompression is to be defined.


Subject(s)
Neurosurgeons , Osteopetrosis/diagnostic imaging , Osteopetrosis/surgery , Physician's Role , Skull/diagnostic imaging , Skull/surgery , Humans , Imaging, Three-Dimensional/methods , Infant , Male , Surgical Flaps
14.
Bull Cancer ; 103(11S): S273-S275, 2016 Nov.
Article in French | MEDLINE | ID: mdl-27776733

ABSTRACT

In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country. Our article discusses the updates and modifications for the 2016 version of the national patient follow-up care logbook.


Subject(s)
Aftercare , Hematopoietic Stem Cell Transplantation/standards , Records/standards , Adult , Child , France , Humans , Societies, Medical , Transplantation, Homologous/standards
15.
Bull Cancer ; 102(7-8): 648-55, 2015.
Article in French | MEDLINE | ID: mdl-25962541

ABSTRACT

Under the long-term monitoring of patients treated in childhood or adolescence for cancer, we present in this article the long-term monitoring and therefore possible effects of patients who underwent allergenic hematopoietic stem cell transplantation. This article is based on a collaborative effort organized by the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC), which took place during the 4th day of allograft harmonization practices. Patients affected are children and young adults (0-25 years). We defined the monitoring effects beyond 1 year post-transplant. Our recommendations are based on a literature review, in line with the Leucémie Enfant Adulte (LEA) study cohort of long-term monitoring of patients treated for hematological malignancies in childhood, grafted or not. It became important to determine the nature of problems, their risk factors, frequency and monitoring necessary to implement for their detection. We will not address the therapeutic management of sequelae.


Subject(s)
Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Adolescent , Adult , Allografts , Bone Diseases/etiology , Bone Diseases, Metabolic/etiology , Child , Child, Preschool , Endocrine System Diseases/etiology , Follow-Up Studies , Heart Diseases/etiology , Humans , Infant , Infant, Newborn , Kidney Diseases/etiology , Lung Diseases/etiology , Metabolic Syndrome/etiology , Osteonecrosis/etiology , Osteoporosis/etiology , Skin Diseases/etiology , Young Adult
16.
Orphanet J Rare Dis ; 9: 162, 2014 Oct 29.
Article in English | MEDLINE | ID: mdl-25496809

ABSTRACT

Allogeneic hematopoietic stem cell transplantation is mainly indicated in bone marrow dysfunction related to blood diseases, but also in some rare diseases (adrenoleucodystrophy, mitochondrial neurogastrointestinal encephalomyopathy or MNGIE...). After decades, this treatment has proven to be efficient at the cost of numerous early and delayed side effects such as infection, graft-versus-host disease, cardiovascular complications and secondary malignancies. These complications are mainly related to the conditioning, which requires a powerful chemotherapy associated to total body irradiation (myelo-ablation) or immunosuppression (non myelo-ablation). Among side effects, the endocrine complications may be classified as 1) hormonal endocrine deficiencies (particularly gonado- and somatotropic) related to delayed consequences of chemo- and above all radiotherapy, with their consequences on growth, puberty, bone and fertility); 2) auto-immune diseases, particularly dysthyroidism; 3) secondary tumors involving either endocrine glands (thyroid carcinoma) or dependent on hormonal status (breast cancer, meningioma), favored by immune dysregulation and radiotherapy; 4) metabolic complications, especially steroid-induced diabetes and dyslipidemia with their increased cardio-vascular risk. These complications are intricate. Moreover, hormone replacement therapy can modulate the cardio-vascular or the tumoral risk of patients, already increased by radiotherapy and chemotherapy, especially steroids and anthracyclins... Therefore, patients and families should be informed of these side effects and of the importance of a long-term follow-up requiring a multidisciplinary approach.


Subject(s)
Disease Management , Endocrine System Diseases/therapy , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Metabolic Diseases/therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Endocrine System Diseases/diagnosis , Endocrine System Diseases/etiology , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/trends , Hormone Replacement Therapy/methods , Hormone Replacement Therapy/trends , Humans , Metabolic Diseases/diagnosis , Metabolic Diseases/etiology
17.
Br J Haematol ; 165(3): 392-401, 2014 May.
Article in English | MEDLINE | ID: mdl-24479958

ABSTRACT

Minimal residual disease (MRD) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia (ALL). Haematopoietic cell transplantation is a treatment option for patients at high risk of relapse. Between 2005 and 2008, we conducted a prospective study evaluating the feasibility and efficacy of the reduction of immunosuppressive medication shortly after a non-ex vivo T depleted myeloablative transplantation. Immunoglobulin (Ig)H/T-cell receptor MRD 30 d before transplant could be obtained in 122 of the 133 cases of high-risk paediatric ALL enrolled. There were no significant demographic differences except remission status (first or second complete remission) between the 95 children with MRD <10(-3) and the 27 with MRD ≥10(-3) . Multivariate analysis identified sex match and MRD as being significantly associated with 5-year survival. MRD ≥10(-3) compromised the 5-year cumulative incidence of relapse (43·6 vs. 16·7%). Complete remission status and stem cell source did not modify the relationship between MRD and prognosis. Thus, pre-transplant MRD is still a major predictor of outcome for ALL. The MRD-guided strategy resulted in survival for 72·3% of patients with MRD<10(-3) and 40·4% of those with MRD ≥10(-3).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Neoplasm, Residual/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adjuvants, Immunologic/administration & dosage , Adolescent , Child , Child, Preschool , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Male , Neoplasm, Residual/immunology , Neoplasm, Residual/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Prognosis , Prospective Studies , Remission Induction , Treatment Outcome
18.
Biol Blood Marrow Transplant ; 18(7): 1080-9, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22212513

ABSTRACT

This study investigated the impact of human herpesvirus type 6 (HHV6) reactivation within 100 days of allogeneic stem cell transplantation (allo-SCT) on patient outcomes. HHV6 plasma loads were monitored weekly by quantitative PCR. Of 235 consecutive patients, 112 (48%) had an early positive HHV6 PCR test (group A) and 123 (52%) did not (group B). HHV6 reactivation was less frequent in patients who received reduced-intensity conditioning (P = .028). In group A, only 6 patients (5%) were asymptomatic; the most common clinical manifestations were fever (n = 60), skin rash (n = 57), diarrhea (n = 51), pulmonary complications (n = 19), and neurologic disorders (n = 12). Compared with the patients in group B, those in group A experienced delayed platelet engraftment (P = .003) and more frequent grade II-IV acute graft-versus-host disease (GVHD) (47% versus 30% in group B; P = .009). In multivariate analysis, the most important factors influencing the development of grade II-IV acute GVHD development were early HHV6 reactivation (P = .03) and unrelated donor status (P < .001). HHV6 reactivation adversely influenced 6-month survival (P = .04). Of the 38 evaluable patients receiving antiviral treatment, 34 had a significantly decreased HHV6 load. Our findings indicate that HHV6 reactivation after allo-SCT is associated with delayed platelet engraftment, early posttransplantation mortality, and the development of acute GVHD. Careful monitoring of HHV6 by PCR is warranted during the early posttransplantation period.


Subject(s)
DNA, Viral/drug effects , Graft vs Host Disease/virology , Hematopoietic Stem Cell Transplantation , Herpesvirus 6, Human/physiology , Roseolovirus Infections/virology , Transplantation Conditioning/methods , Adolescent , Adult , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Blood Platelets/immunology , Child , Child, Preschool , Female , Graft vs Host Disease/complications , Graft vs Host Disease/drug therapy , Graft vs Host Disease/mortality , Herpesvirus 6, Human/drug effects , Humans , Male , Middle Aged , Roseolovirus Infections/complications , Roseolovirus Infections/drug therapy , Roseolovirus Infections/mortality , Severity of Illness Index , Survival Analysis , Transplantation, Homologous , Unrelated Donors , Viral Load/immunology , Virus Activation/immunology
19.
Pediatr Blood Cancer ; 55(4): 662-7, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20806364

ABSTRACT

BACKGROUND: The prognosis of febrile neutropenia (FN) in childhood cancer has been considerably improved by the intensification of treatment, including systematic hospitalization and broad-spectrum antibiotics. As only few children present with a severe bacterial infection (SBI), clinical decision rules have been developed to distinguish those at risk for SBI. The aim of this study was to evaluate the reproducibility of six clinical decision rules proposed in the literature and to compare their performance. METHODS: This retrospective two-center cohort study included all episodes of chemotherapy-induced FN in children admitted between January 2005 and December 2006. Each rule was applied to our patients. Their sensitivity (Se) and specificity (Sp) were calculated and compared with the authors' results, to assess reproducibility. The most predictive rule was defined in advance as that yielding 100% Se, the highest Sp, and the greatest simplicity for bedside application. RESULTS: Three hundred seventy-seven episodes of FN in 167 patients were collected; 64 episodes were associated with SBI, including 36 with bacteremia. Four of the six rules were reproducible, but none were able to be validated. The most predictive rule for bacteremia had 96% Se (95% confidence interval (CI): 79-99%) and 25% Sp (95% CI: 19-33%), and the most predictive rule for SBI had 95% Se (95% CI: 87-98%), but no power of discrimination (Sp = 5%, 95% CI: 3-8%). CONCLUSION: This study emphasizes the difficulty in identifying standardized decision rules in the management of a condition with numerous clinical variables like FN.


Subject(s)
Antineoplastic Agents/adverse effects , Bacterial Infections/etiology , Fever/complications , Neutropenia/complications , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Male , Reproducibility of Results , Retrospective Studies , Risk Factors
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