Figure 1 - available via license: Creative Commons Attribution 2.0 Generic
Content may be subject to copyright.
Overall survival of Fanconi Anemia patients. 53.63% (95% confidence interval: 29.53%-72.74%) The leading cause of death was GVHD with 5 cases; 4 acute and 1 chronic, responsible for 50% of deaths reported. The most frequent reason for death in the first month was sepsis (1 out of 2 cases died of sepsis, and the other died of sepsis and Diabetic Ketoacidosis; DKA simultaneously) and for the 3-month was acute GVHD. Other causes of death were hepatic mass (a mass lesion with radiologic findings in favor of malignancy but the patient died before the biopsy was taken) and renal failure. There is a significant relationship between mortality and grade 3 or 4 acute GVHD (log-rank; p- value=0.02). There were no association between overall survival and age, sex, liver function test, Hb and white blood cell, platelet count and bone marrow cellularity before transplant (cox-regression).
Source publication
Background & objectives: Fanconi anemia (FA) is a rare genetic disorder caused by an impaired DNA repair mechanism which leads to an increased tendency toward malignancies and progressive bone marrow failure. The only curative management available for hematologic abnormalities in FA patients is hematopoietic stem cell transplantation (HSCT). This s...
Citations
... In our previous studies, outcomes of allogeneic HSCT on adult patients with paroxysmal nocturnal hemoglobinuria (PNH) and Fanconi anemia were evaluated. 11,12 It has been reported that in our patients with severe aplastic anemia between 1991 and 2011, 3-year overall survival and disease-free survival of allogeneic HSCT was 82% and 75% respectively. 13 In the present study, we evaluated the long-term survival rates among patients between 40 and 50 years with severe aplastic anemia treated with allogeneic HSCT in the Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran, Iran. ...
The front-line treatment for patients under the age of 40 with severe aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-identical sibling donor. However, in severe AA patients older than 40 years, allogeneic HSCT has been found to be associated with increased treatment-related mortality and toxicity, even when matched sibling donors are used. We report our institutional experience with allogeneic HSCT in severe AA patients between 40 and 50 years. A total of 19 patients with severe AA were included in the study. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method. The mean age of patients at the time of transplant was 43.79 years, and 57.9% were male. The mortality rate was 36.8%, due to infection (10.5%), relapse (15.8%), and renal failure (5.3%) in all cases. Acute GVHD occurred in five patients (26.3%), and chronic GVHD occurred in two patients (10.5%). The 5-year OS was 62% and the 5-year DFS was 52%. We found that the patient's age, platelet level before transplantation, and the number of CD3 cells infused for each transplant were independent prognostic factors for OS, and the age and sex of the patient, the graft rejection, and platelet level before transplantation were significant prognostic factors associated with DFS. We recommend that immunosuppressive therapy should be considered as a first-line treatment in patients with severe AA who are over 40 years of age. Allogeneic HSCT can be considered as a valid alternative option in patients whose suppression therapy fails.
... A study from Iran included patients 20 years or older [21]. Indications for HCT were severe bone marrow failure or blood products transfusion dependency, all the patients included had a full HLA-matched sibling donor. ...
Hematopoietic cell transplant (HCT) activity is increasing worldwide due to safer techniques, widening indications, and more availability of donors. New HCT centers have recently been established in many developing countries including Asian and African countries. Due to limited resources, logistic, political, and social issues in developing countries, the treatment of orphan diseases like graft-versus-host disease (GVHD) can be challenging. We intended to delineate the current issues that institutions and clinicians face in managing GVHD. We conducted a comprehensive systematic electronic review of peer-reviewed published articles on GVHD management in developing countries. We used PubMed, Cochrane, and Embase databases as our primary source of data. Studies that were included described the treatments for both acute and chronic GVHD. Consensus on the use of high-dose methyl-prednisone and prednisolone as the initial therapy was widely accepted and used in practice. Socio-economic factors were found to be the major factor involved in GVHD management in lower income patients. Delayed diagnosis and treatment, lack of availability of healthcare professionals, lack of knowledge among cancer patients, and poverty are major concerns in the developing world. For optimal management, HCT programs should develop systems in place for long-term follow-up of HCT survivors and have a low threshold to initiate treatments for GVHD early. Awareness and health policy programs must be initiated at the grass-root level for long-term management of these survivors in developing countries.
... Fanconi anemia (FA) is a rare recessive genetic disease, usually inherited in an autosomal recessive manner, linked to bone marrow failure and an increased risk of developing a tumor. 1 FA patients are more prone to presenting morphological and endocrine abnormalities, such as bone deformities, cardiac and kidney malformation, hyperpigmentation, glucose intolerance, changes in glycemic control, dyslipidemia, hypothyroidism and growth hormone deficiency. 2 The only hematology treatment that offers a potential cure for this disorder is hematopoietic stem cell transplantation (HSCT), which aims to restore the impaired bone marrow. [1][2][3] Some conditions may affect the success rate of HSCT, such as the stage of the disease, the type of transplant, the origin of donor stem cells and histocompatibility, the conditioning regimen, age, previous treatment, and nutritional status of the patient. 4 Moreover, immunosuppression and the toxicity of the conditioning regimen have negative effects, in particular in respect to infections, bleeding, constipation, diarrhea, mucositis, nausea, and emesis. ...
... 4 Moreover, immunosuppression and the toxicity of the conditioning regimen have negative effects, in particular in respect to infections, bleeding, constipation, diarrhea, mucositis, nausea, and emesis. 3 In addition to the characteristic outcomes of the disease, such as short stature, transplanted patients with FA can be underweight, present increased growth problems and dyslipidemia, whereas changes in glycemic and hormone control may result in an overweight condition or even obesity. 5 Malnutrition has substantial prognostic and socioeconomic implications for patients and caregivers. ...
... Furthermore, an analysis of the ROC curve, even considering only the potentially healthier patients since they were evaluated more than 6 months after the transplant, showed that more than one and a half years would be necessary to reach normal weight parameters according to their BMI. Studies indicate that from 22% to 38% of FA patients are underweight 3,16 ; this may occur due to anatomical alterations of the gastrointestinal tract, chronic inflammation, infection, or as consequences of pharmacological treatment, resulting in early satiety, reflux, nausea, emesis, and diarrhea. 17 This study found similar results: 20% of non-transplanted children and adolescents had decreased BMI. ...
Introduction:
Fanconi anemia is a rare genetic disease linked to bone marrow failure; a possible treatment is hematopoietic stem cell transplantation. Changes in the nutritional status of Fanconi anemia patients are not very well known. This study aimed to characterize body composition of adult, children and adolescent patients with Fanconi anemia who were submitted to hematopoietic stem cell transplantation or not.
Methods:
This cross-sectional study enrolled 63 patients (29 adults and 34 children and adolescents). Body composition was assessed based on diverse methods, including triceps skin fold, arm circumference, arm muscle area and bioelectrical impedance analysis, as there is no established consensus for this population. Body mass index was also considered as reference according to age.
Results:
Almost half (48.3%) of the transplanted adult patients were underweight considering body mass index whereas eutrophic status was observed in 66.7% of the children and adolescents submitted to hematopoietic stem cell transplantation and in 80% of those who were not. At least 50% of all groups displayed muscle mass depletion. Half of the transplanted children and adolescents presented short/very short stature for age.
Conclusion:
All patients presented low muscle stores, underweight was common in adults, and short stature was common in children and adolescents. More studies are needed to detect whether muscle mass loss measured at the early stages of treatment results in higher risk of mortality, considering the importance of muscle mass as an essential body component to prevent mortality related to infectious and non-infectious diseases and the malnutrition inherent to Fanconi anemia.
... FA cells are hypersensitive to DNA cross-linking agents that lead to chromosomal instability [3,4]. This causes severe toxicity from the conventional conditioning regimen chemotherapy that's used for the transplantation of those patients [5] and variable regimens have been suggested to achieve a well-tolerated conditioning regiment to these patients [6][7][8]. ...
... FA cells are hypersensitive to DNA cross-linking agents that lead to chromosomal instability [3,4]. This causes severe toxicity from the conventional conditioning regimen chemotherapy that's used for the transplantation of those patients [5] and variable regimens have been suggested to achieve a well-tolerated conditioning regiment to these patients [6][7][8]. ...
Introduction: Fanconi’s anemia (FA) is a rare genetic disorder. Patients with this disorder have progressive bone marrow failure, congenital abnormalities and are vulnerable to malignancy.
Aim: Explaining our single center experience regarding ATG based conditioning regimen that’s used for the transplantation of patients with Fanconi’s Anemia.
Materials and methods: Sixty-three patients with Fanconi anemia (FA) underwent stem cells transplantation from matched siblings, either from peripheral blood (PBSCsT) in fifty nine patients , or bone marrow in four patients, according to donors’ age and/weight. Mean age at BMT was 11.2 years. Conditioning regimen consisted of low-dose cyclophosphamide 5 mg/kg/d from d-5 to d-2 , fludarabin 120mg/m2 from d-10 to d-6, CSA: 3mg/ kg/d start from d –1 and Antithymocyte globulin (ATG) was added in the pre-transplant as well as the post-transplant period at a total dose of 30 mg/kg as follows: 5mg/ kg/d (from d-4to d-1), 2.5mg/kg (d+1,d+3, d+6, d+11). We divided our patients into two cohorts based on age. The first cohort aged 12 years and older and the second cohort included patients younger than 12 years old. We also studied the overall survival according to the source of stem cells (Bone Marrow vs. Peripheral blood stem cells).
Results: Engraftment has been achieved in 49 (77%) patients with a mean time of 13.2 days (range, 8-26 days) SD= 3.8. The mean time for a self-sustaining platelet count of > 25 ×109/l was 14.6 days (range, 8-30 days) SD= 4.5. Eight (12.7 %) patients developed acute GVHD; none developed extensive chronic GVHD, 4 Patients developed only limited chronic GVHD. Fourteen patients died before engraftment.
Conclusion: Our current results underline the importance of using ATG in the conditioning regimen for the transplantation of patients with Fanconi’s anemia.
... FA cells are hypersensitive to DNA cross-linking agents that lead to chromosomal instability [3,4]. This causes severe toxicity from the conventional conditioning regimen chemotherapy that's used for the transplantation of those patients [5] and variable regimens have been suggested to achieve a well-tolerated conditioning regiment to these patients [6][7][8]. ...
p> Introduction: Fanconi’s anemia (FA) is a rare genetic disorder. Patients with this disorder have progressive bone marrow failure, congenital abnormalities and are vulnerable to malignancy.
Aim: Explaining our single center experience regarding ATG based conditioning regimen that’s used for the transplantation of patients with Fanconi’s Anemia.
Materials and methods: Sixty-three patients with Fanconi anemia (FA) underwent stem cells transplantation from matched siblings, either from peripheral blood (PBSCsT) in fifty nine patients , or bone marrow in four patients, according to donors’ age and/weight. Mean age at BMT was 11.2 years. Conditioning regimen consisted of low-dose cyclophosphamide 5 mg/kg/d from d-5 to d-2 , fludarabin 120mg/m2 from d-10 to d-6, CSA: 3mg/ kg/d start from d –1 and Antithymocyte globulin (ATG) was added in the pre-transplant as well as the post-transplant period at a total dose of 30 mg/kg as follows: 5mg/kg/d (from d-4to d-1), 2.5mg/kg (d+1,d+3, d+6, d+11). We divided our patients into two cohorts based on age. The first cohort aged 12 years and older and the second cohort included patients younger than 12 years old. We also studied the overall survival according to the source of stem cells (Bone Marrow vs. Peripheral blood stem cells).
Results: Engraftment has been achieved in 49 (77%) patients with a mean time of 13.2 days (range, 8-26 days) SD= 3.8. The mean time for a self-sustaining platelet count of > 25 ×109/l was 14.6 days (range, 8-30 days) SD= 4.5. Eight (12.7 %) patients developed acute GVHD; none developed extensive chronic GVHD, 4 Patients developed only limited chronic GVHD. Fourteen patients died before engraftment.
Conclusion: Our current results underline the importance of using ATG in the conditioning regimen for the transplantation of patients with Fanconi’s anemia.</p
Aplastic anemia is disease characterized by pancytopenia with a hypocellular marrow. Allogeneic hematopoietic stem cell transplantation (allo SCT) from an HLA-matched sibling donor (MSD) is the treatment of choice for patients with severe aplastic anemia (SAA) and age less than 40 years old. Bone marrow is the preferred source of stem cells in patients younger than 20 years of age as the rates of chronic GVHD and overall mortality are increased after SCT with peripheral blood stem cells. Graft rejection has been one of the major limitations of allo SCT for SAA, occurring more frequently than in other transplant indications like leukemia. The preferred conditioning regimens include fludarabine/cyclophosphamide/anti-thymocyte globulin (FluCyATG) and CyATG. Young patients lacking MSD should be considered for matched unrelated donor (MUD) SCT upfront. Haplo SCT is an alternative treatment for SAA patients lacking MSD/MUD and those who are refractory to immunosuppressive therapy. Allo SCT is also the only curative treatment for PNH. The primary indications for allo SCT in PNH are bone marrow failure, recurrent thrombosis, and uncontrollable hemolysis. Fanconi anemia (FA) is an inherited bone marrow failure syndrome that also requires treatment with allo SCT.
Posterior reversible encephalopathy syndrome (PRES) is one of the most common neurologic complications following hematopoietic stem cell transplantation (HSCT). We aimed to evaluate incidence, clinical, and imaging features of PRES in pediatric patients with FA following HSCT. This prospective study was carried out on all post-HSCT patients with underlying FA disease between 2014 and 2017. Brain CT scan and MRI were performed in all individuals who developed neurologic symptoms. The diagnosis of PRES had done based on clinic-radiological evidence. Follow-up MRI was carried out in all patients with PRES within two months. Forty-one patients with FA (28 males, mean age: 8.19±3.25 years) were enrolled. Out of 15 patients with acute neurologic symptoms, PRES was diagnosed in 9 individuals (21.95%). The occurrence of PRES was significantly higher among patients who had a donor with a one-locus mismatch (p-value: 0.02). Donor relation, stem cell source, and GvHD grading did not have any significant association with the development of PRES. MRI showed asymmetric vasogenic edema in five patients, overt infarct in one, and foci of micro-hemorrhage in three individuals that one of them developing hemorrhagic infarct. The patient expired shortly, while persistent micro-hemorrhage was noted on the other two patients. The result of our study demonstrated the risk of developing PRES after HSCT is higher in FA compared to other diseases reported in articles (21.95% vs. 1-10%), and in contrast to its term, it might be irreversible and has adverse effects on the results of HSCT. Increased vascular and endothelial fragility in FA may impact on the higher frequency of PRES in these individuals.
Aim:
To characterize the clinical indications of females (<15 years old) undergoing ovarian tissue cryopreservation (OTC) through the Oncofertility Consortium's National Physicians Cooperative (OC-NPC).
Patients & methods:
The clinical indications of 114 females who underwent OTC were classified, and their incidence was compared with childhood cancer databases.
Results:
Leukemias/myeloproliferative diseases/myelodysplastic diseases and hemoglobinopathies were the most prevalent oncologic and nononcologic indications for OTC, respectively. The frequencies of malignant bone tumors and soft tissue and other extraosseous sarcomas were higher in the OC-NPC cohort relative to the general population, while CNS/intracranial/intraspinal neoplasms, retinoblastoma and hepatic tumors were lower.
Conclusion:
Those opting for OTC through the OC-NPC are at highest fertility risk, indicating that the appropriate patient populations are being identified. [Formula: see text].
