Bone Marrow Transplantation In Children Research Articles

Income Level and Insurance Status Are Correlated with Medical Non-Compliance after Bone Marrow Transplant in Children

Income Level and Insurance Status Are Correlated with Medical Non-Compliance after Bone Marrow Transplant in Children

Optimizing of the isolation of hematopoietic stem cell in bone marrow transplantation in children

Most of collected hematopoietic stem cell (HSCs) products need processing in order to isolate stem cells, squeeze out of plasma and erythrocytes. There are two main aims for bone marrow (BM) enrichment: reduction of immunogenicity of AB0 incompatible transplants and/or preventing toxicity of hemolysis during cryopreservation. In our center we have implemented two methods for BM enrichment: manual technic using 10 % HAES (hydroxyethyl starch) and automatic cell separator. In order to optimize the process, we examined retrospectively the parameters which could have a great impact on final efficiency of engraftment, such as reduction of hematocrit, CD34 + , WBC recovery and cell viability. This study was a retrospective analysis of 46 pediatric patients (pts) who underwent autologous or allogeneic HSCT. There were performed 27 procedures using cell separator and 19 with HAES technique. This study showed that cell separator processing is significantly less damaging for stem cells than widely longer, manual HAES technique. Comparing RBC depletion and WBC recovery both used techniques are same efficient and good enough but we found out a significant difference in the efficiency of CD34 + recovery which was much higher in a technique of cell separator. We examined also the effect of addition of packed red blood cells (PRBCs) to the BM on purifying and efficiency of HSCs isolation. Doing so it decreased only the WBC recovery during sell separator processing. To sum up after series of analyzes we found out that cell separator is more convenient than HAES technique in most of considered aspects. Furthermore, cell separator use is cheaper and needs less time for processing.

Haploidentical vs. HLA-matched donor hematopoietic stem-cell transplantation for pediatric patients with acute lymphoblastic leukemia in second remission: A collaborative retrospective study of the Spanish Group for Bone Marrow Transplantation in Children (GETMON/GETH) and the Spanish Childhood Relapsed ALL Board (ReALLNet).

Studies addressing the role of haploidentical as alternative to HLA-matched donors for stem cell transplantation (SCT) often include patients with diverse hematological malignancies in different remission statuses. We compared outcomes of children with acute lymphoblastic leukemia (ALL) undergoing SCT in second complete remission (CR2) from haploidentical (n = 25) versus HLA-matched donor (n = 51). Patients were equally distributed across both groups according to age, immunophenotype, time to and site of relapse, relapse risk-group allocation, and minimal residual disease (MRD) before SCT. Incidence of graft failure, acute graft versus host disease (GVHD), and other early complications did not differ between both groups. We found no differences in overall survival (58.7% versus 59.5%; p = .8), leukemia free survival (LFS) (48% versus 36.4%; p = .5), event free survival (40% versus 34.4%; p = .69), cumulative incidence (CI) of subsequent relapse (28% versus 40.9%; p = .69), treatment related mortality (24% versus 23.6%; p = .83), CI of cGVHD (4.5% versus 18.7%; p = .2), and chronic GVHD-free and leukemia-free survival (44% versus 26.3%; p = .3) after haploidentical donor SCT. Chronic GVHD (HR = 0.09; p=.02) had protective impact, and MRD ≥ 0.01% before SCT (HR = 2.59; p=.01) had unfavorable impact on LFS. These results support the role of haploidentical donor SCT in children with ALL in CR2.

Severe, life-threatening, and fatal chronic health conditions after allogeneic blood or marrow transplantation in childhood.

A comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied. Seven hundred eighty-nine allogeneic BMT recipients who had survived ≥2years after BMT performed between 1974 and 2014 at age <22years and 690 siblings completed a 255-item survey self-reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life-threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3-5 conditions. Logistic regression was used to estimate the risk of grade 3-4 conditions in BMT recipients who were alive at the time of this study compared with siblings. The median age at transplantation was 11.3years (range, 0.4-22.0 years), and the median length of follow-up was 11.7years (range, 2.0-45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35years, the cumulative incidence of a grade 3-4 condition was 53.8% (95% CI, 46.7%-60.3%). The adjusted odds ratio of a grade 3-4 condition was 15.1 in survivors (95% CI, 9.5-24.0) compared with siblings. The risk of a grade 3-5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01-1.05) and was higher among females (HR, 1.27; 95% CI, 1.02-1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27-2.31), and those reporting chronic graft-versus-host disease (HR, 1.38; 95% CI, 1.09-1.74). Two-year survivors of allogeneic BMT in childhood have an increased risk of grade 3-4 chronic health conditions compared with siblings, suggesting the need for long-term follow-up.

Risk Factors for Donor-Type Aplasia after Bone Marrow Transplant in Children with Acquired Bone Marrow Failure

Graft failure is a majorcause of severe aplasia after bone marrow transplant (BMT) in patients with acquired bone marrow failure (aBMF). However, we have encountered several patients with aBMF who showed persistent aplasia with full donor chimerism after BMT (donor-type aplasia). The mechanism and risk factors of donor-type aplasia are not clarified.To clarify risk factors for donor-type aplasia, we reviewed clinical data for 50 patients with aBMF who received allogeneic BMT at our hospital from August 1997 to July 2016. Out of the 50 patients, there were 32 males and 18 females. The median age at BMT was 11 years (range, 1-19 years). We retrospectively reviewed BM smears and histopathological samples at the time of BMT according to the 2008 WHO classification. Out of the 50 patients, 26 were classified as aplastic anemia (AA) and 24 as refractory cytopenia of childhood (RCC). Twenty patients received BMT from related donors including 5 human leukocyte antigen (HLA)-mismatched donors and 30 patients from unrelated donors including 15 HLA-mismatched donors. Conditioning regimens including cyclophosphamide (CY) and antithymocyte globulin (ATG) with or without low dose total body irradiation (TBI) were used for 31, fludarabine (FLU) and half dose of CY with low dose TBI were used for 15, and FLU and melphalan (MEL) with low dose TBI were used for 4 patients. Donor-type aplasia was defined as hypocellular BM with persistent cytopenia (hemoglobin <80 g/L, neutrophils <1x109/L, or platelets <50x109/L) for >6 months after achieving engraftment with full donor chimerism. To reveal risk factors of donor type aplasia, we analyzed variables as follows; age at BMT, gender, BM morphology at BMT, year performed BMT, period from diagnosis to BMT, times of red blood cell (RBC) transfusion, HLA disparity, transfused BM cell dose, conditioning regimen, graft versus host disease (GVHD), and viral infection.Out of the 50 patients, 10 patients developed late graft failure. Eight out of them developed donor-type aplasia. Out of the 8 patients, there were 5 males and 3 females. The median age at BMT was 10 years (range, 5-13 years). Bone marrow findings of all patients showed RCC at the time of BMT. Two of them received BMT from HLA-mismatched donors and 3 from unrelated donors. FLU/CY regimen was used for 6 patients, while CY/ATG regimen was used for 2 patients. All patients received low dose TBI. Three patients received BMT with <3x108/kg cell dose. Acute GVHD were observed in 2 patients and one of them developed chronic GVHD. Five patients showed cytomegalovirus antigenemia in their blood and received ganciclovir. Two patients developed Epstein-Barr virus reactivation and received rituximab. The onset of donor-type aplasia ranged from day 46 to day 710 after BMT. Five patients needed RBC or platelet transfusion, or granulocyte-colony stimulating factor (G-CSF). Donor-type aplasia continued for more than 3 years in 5 patients. Donor-type aplasia was improved spontaneously in 6 patients, ranging from 460 days to 3539 days after BMT. Only one patient underwent haploidentical stem cell transplant (SCT) from her father because of the development of severe pneumonia. She achieved engraftment after second SCT. All patients who developed donor type aplasia are alive. Cumulative incidence (CI) of donor-type aplasia was significantly higher in patients who had RCC (32%) than in patients who had AA (4%) (p = 0.013), and CI of donor-type aplasia was also significantly higher in patients who received FLU/CY regimen (44%) than in patients who received non-FLU/CY regimen (6%) (p = 0.003). Multivariate analysis confirmed that RCC (hazard ratio 8.8, 95% CI 1.1-68, p = 0.037) and FLU/CY regimen (hazard ratio 7.7, 95% CI 1.5-38, p = 0.013) were significant risk factors for donor-type aplasia.In conclusion, FLU/CY regimen is not suitable for children with RCC as a conditioning regimen of BMT. It is important to evaluate BM morphology to decide conditioning regimens for children with aBMF. The establishment of the optimal conditioning regimens for children with aBMF on the basis of the BM morphology is essential. DisclosuresNo relevant conflicts of interest to declare.

Matched sibling donor stem cell transplantation for sickle cell disease: Results from the Spanish group for bone marrow transplantation in children.

The prevalence of sickle cell disease (SCD) in Spain is markedly inferior compared with other European and Mediterranean countries. However, the diagnosis of new patients with SCD is expected to increase. In this multicenter retrospective study, we analyze the hematopoietic stem cell transplantation (HSCT) results obtained in Spain. Forty-five patients who underwent a matched sibling donor (MSD) HSCT between 1999 and 2018 were included. Primary endpoint was event-free survival (EFS), and secondary endpoints included acute and chronic graft-versus-host disease (GvHD) and overall survival (OS). Bone marrow was the most frequent stem cell source (93.3%). Most patients received a conditioning regimen based on busulfan and cyclophosphamide (69%). Cumulative incidence of grade III-IV acute GvHD and chronic GvHD was 6.8% (95% CI: 2.3%-20.1%) and 5.4% (95% CI: 1.38%-19.9%), respectively. EFS and overall survival (OS) at 3years post-HSCT were 89.4% (95% CI: 73.9%-95.9%) and 92.1% (95% CI: 77.2%-97.4%), respectively. All patients aged≤5 presented 100% EFS and OS. An early referral to HSCT centers should be proposed early in life, before severe complications occur. MSD HSCT should be considered a curative option for all patients aged≤5years and for older pediatric patients who present complications derived from the disease.

Survival and toxicity outcomes of hematopoietic stem cell transplantation for pediatric patients with Fanconi anemia: a unified multicentric national study from the Spanish Working Group for Bone Marrow Transplantation in Children.

Hematopoietic stem cell transplantation (HSCT) is currently the only curative option for hematological manifestations in patients with Fanconi anemia (FA). We report the outcome of 34 patients with FA inside a collaborative multicenter national study based on recommendations of Spanish Working Group for Bone Marrow Transplantation in Children (GETMON) between 2009 and 2016. Fludarabine-based conditioning regimen was carried out in all patients, with low dose total body irradiation in unrelated transplants. Disease status before HSCT was bone marrow failure (BMF) in 30 patients and myelodysplastic syndrome (MDS) in four. Donors were matched siblings donors (MSD) in 18, matched unrelated donors (MUD) in 15, and one haploidentical donor. All except one patient engrafted. Cumulative incidence of grades II-IV acute graft-versus-host disease (GVHD) was 29% and 11% for chronic GVHD. Median follow-up after HSCT was 6.5 years. Seven patients (21%) died due to transplant-related causes, two (6%) because of MDS relapse, and one (3%) after a squamous cell carcinoma. Overall survival (OS) was 73% at 5 years post-transplant, with no differences between MSD and MUD transplants. OS for patients with BMF was 80% while for MDS was 25%. Our data suggest HSCT can cure hematologic manifestations of most FA patients with BMF.

Risk factors for secondary poor graft function after bone marrow transplantation in children with acquired aplastic anemia.

In patients with acquired AA, PGF is a major cause of cytopenia after hematopoietic stem cell transplantation. An increased incidence of PGF, especially sPGF, has been noted after the introduction of the FLU/CY regimen in children with acquired AA. To clarify the risk factors for sPGF, the clinical data of 49 patients (median age, 11years; range, 1-19years) with AA who received allogeneic BMT at Nagoya University Hospital from 1997 to 2016 were analyzed. Out of the 49 patients, 7 developed sPGF, and the 5-year CI was 0.15 (95% CI, 0.04-0.25). Five received the FLU/CY regimen, and the 5-year CI of sPGF was significantly higher in patients who received the regimen (0.36; 95% CI, 0.12-0.62) than in those who were conditioned with the non-FLU/CY regimen (0.06; 95% CI, 0.01-0.17; P=.01). The multivariate analysis confirmed that the FLU/CY regimen (hazard ratio, 6.12; 95% CI, 1.16-32.4; P=.03) was a significant risk factor for sPGF. sPGF improved spontaneously without stem cell boost infusions in 5 patients, ranging from 460 to 3539days after BMT. The 10-year CI of the spontaneous trilineage recovery was 0.83 (95% CI, 0.00-0.97), and all 7 patients are alive. The FLU/CY regimen was identified as a risk factor for the sPGF development in patients with AA. The establishment of the optimal conditioning regimens for children with AA is warranted.

Conditioning regimen for allogeneic bone marrow transplantation in children with acquired bone marrow failure: fludarabine/melphalan vs. fludarabine/cyclophosphamide.

Fludarabine/cyclophosphamide-based conditioning regimens are standard in bone marrow transplantation (BMT) for acquired bone marrow failure in children, however, graft failure may occur. Using the data from a nationwide transplantation registry, we compared the outcomes of children aged <16 years with acquired aplastic anemia and refractory cytopenia of childhood who underwent allogeneic BMT with either fludarabine/melphalan (n = 71) or fludarabine/cyclophosphamide (n = 296) between 2000 and 2016. The fludarabine/melphalan regimen provided excellent outcomes, with 3-year overall survival and failure-free survival rates of 98% and 97%, respectively. The 83% 3-year failure-free survival in the fludarabine/cyclophosphamide group was significantly inferior (P = 0.002), whereas the overall survival did not differ between the two groups. Late graft failure was the most common cause of treatment failure in the fludarabine/cyclophosphamide group, which experienced a significantly higher incidence of late graft failure than the fludarabine/melphalan group (11% vs. 3%; P = 0.035). Multivariate analyses showed that the fludarabine/melphalan regimen was associated with a better failure-free survival (hazard ratio [HR] 0.12; P = 0.005) and lower risk of late graft failure (HR 0.16; P = 0.037). Fludarabine/melphalan-based conditioning regimen can be a promising option for children with acquired bone marrow failure receiving BMT.

Pulmonary hypertension after bone marrow transplantation in children.

Pulmonary hypertension is a rare but important cause of mortality after haematopoietic stem cell transplantation (HSCT) in children. This complication is poorly characterised in the literature. We report here a series of children who developed pulmonary hypertension after HSCT. Between January 2008 and December 2015, we retrospectively analysed 366 children who underwent HSCT (age range 0.5-252 months; median 20.3 months). During the post-HSCT course, echocardiography scans motivated by respiratory symptoms identified 31 patients with elevated tricuspid regurgitation velocity (>2.8 m·s-1), confirmed when possible by right heart catheterisation (RHC). 22 patients had confirmed pulmonary hypertension with mean±sd pulmonary arterial pressure 40.1±10 mmHg (range 28-62 mmHg) and pulmonary vascular resistance 17.3±9.2 Wood Units (range 8-42 Wood Units). Among the 13 responders at reactivity test, only one patient responded to calcium channel blockers. Seven patients (32%) died. 15 pulmonary hypertension patients were alive after a mean±sd follow-up of 6.5±2.3 years (range 2-10 years). All survivors could be weaned off pulmonary hypertension treatment after a median follow-up of 5 months (range 3-16). The delay between clinical symptoms and initiation of pulmonary hypertension therapy was significantly longer in patients who subsequently died (mean±sd 33.5±23 days; median 30 days) than in survivors (mean±sd 7±3 days) (p<0.001). Pulmonary hypertension is a severe complication of HSCT with an underestimated incidence and high mortality. Aggressive and timely up-front combination therapy allowed normalisation of pulmonary pressure and improved survival.

Hematopoietic stem cell transplantation in pediatric patients with β-thalassemia and sickle cell disease: An experience of the Spanish Working Group for Bone Marrow Transplantation in Children (GETMON)

Background and objectivesA recently occurring increase of the prevalence of haemoglobinopathies, β-thalassaemia major (TM) and sickle cell disease (SCD) over the last two decades in our country has generated new needs in terms of medical resources for both prevention and treatment of these patients. Allogeneic haematopoietic stem cell transplant (allo-HSCT) is a curative treatment available for patients who have severe haemoglobinopathies. The main objective of this study was to evaluate the results of allo-HSCT in paediatric patients with TM or SCD performed in paediatric haematopoietic transplant units within the Spanish Group of Bone Marrow Transplantation in Children (GETMON). Material and methodsRetrospective review of patients undergoing HSCT in the GETMON units until 2015. ResultsA total of 65 patients were analysed (43 patients were affected with TM and 22 with SCD), who received allo-HSCT in 6 GETMON units between November 1989 and December 2014. Event-free survival three years post-transplant was 81% and overall survival 92% in patients with TM. Event-free survival three years post-transplant was 79% and overall survival 85% in patients with SCD. ConclusionsThe results of this series are comparable to the results of other international series and offer a platform from which to continue trying to improve the evolution of these patients.

Late Mortality after Allogeneic Bone Marrow Transplantation in Childhood for Bone Marrow Failure Syndromes and Severe Aplastic Anemia

Children with bone marrow failure syndromes and severe aplastic anemia (SAA) are treated with allogeneic blood or marrow transplantation (BMT). However, there is a paucity of studies examining late mortality risk after allogeneic BMT performed in childhood for bone marrow failure syndromes and SAA and evaluating how this risk differs between these diseases. We investigated cause-specific late mortality in 2-year survivors of allogeneic BMT for bone marrow failure syndromes and SAA performed before age 22years between 1974 and 2010 at 2 US transplantation centers. Vital status information was collected from medical records, the National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. The standardized mortality ratio (SMR) was calculated using age- sex-, and calendar-specific mortality rates from the Centers for Disease Control and Prevention. Among the 2-year survivors of bone marrow failure syndromes (n = 120) and SAA (n = 147), there were 15 and 19 deaths, respectively, yielding an overall survival of 86.4% for bone marrow failure syndromes and 93.1% for SAA at 15years post-BMT. Compared with the general population, patients with bone marrow failure syndromes were at a higher risk for premature death (SMR, 22.7; 95% CI, 13.1 to 36.2) compared with those with SAA (SMR, 4.5; 95% CI, 2.8 to 7.0) (P < .0001). The elevated relative risk persisted at ≥15years after BMT for both diseases. The hazard of all-cause late mortality was 2.9-fold (95% CI, 1.1 to 7.3) higher in patients with bone marrow failure syndromes compared with those with SAA. The high late mortality risk in recipients of allogeneic BMT in childhood for bone marrow failure syndromes calls for intensified life-long follow-up.

Cerebral Blood Flow and Marrow Diffusion Alterations in Children with Sickle Cell Anemia after Bone Marrow Transplantation and Transfusion.

Hematopoietic marrow hyperplasia and hyperperfusion are compensatory mechanisms in sickle cell anemia. We have observed marrow diffusion and arterial spin-labeling perfusion changes in sickle cell anemia following bone marrow transplantation. We aimed to compare arterial spin-labeling perfusion and marrow diffusion/ADC values in patients with sickle cell anemia before and after bone marrow transplantation or transfusion. We reviewed brain MRIs from patients with sickle cell anemia obtained during 6 consecutive years at a children's hospital. Quantitative marrow diffusion values were procured from the occipital and sphenoid bones. Pseudocontinuous arterial spin-labeling perfusion values (milliliters/100 g of tissue/min) of MCA, anterior cerebral artery, and posterior cerebral artery territories were determined. Territorial CBF, whole-brain average CBF, and marrow ADC values were compared for changes before and after either bone marrow transplantation or transfusion. Bone marrow transplantation and transfusion groups were compared. Two-tailed paired and unpaired Student t tests were used; P < .05 was considered significant. Fifty-three examinations from 17 patients with bone marrow transplantation and 29 examinations from 9 patients with transfusion were included. ADC values significantly increased in the sphenoid and occipital marrow following bone marrow transplantation in contrast to patients with transfusion (P > .83). Whole-brain mean CBF significantly decreased following bone marrow transplantation (77.39 ± 13.78 to 60.39 ± 13.62 ml/100 g tissue/min; P < .001), without significant change thereafter. CBF did not significantly change following the first (81.11 ± 12.23 to 80.25 ± 8.27 ml/100 g tissue/min; P = .47) or subsequent transfusions. There was no significant difference in mean CBF between groups before intervention (P = .22). Improved CBF and marrow diffusion eventuate following bone marrow transplantation in children with sickle cell anemia in contrast to transfusion therapy.

Trasplante de progenitores hematopoyéticos en niños con β-talasemia y enfermedad drepanocítica: experiencia del grupo GETMON

Background and objectivesA recently occurring increase of the prevalence of haemoglobinopathies, β-thalassaemia major (TM) and sickle cell disease (SCD) over the last two decades in our country has generated new needs in terms of medical resources for both prevention and treatment of these patients. Allogeneic haematopoietic stem cell transplant (allo-HSCT) is a curative treatment available for patients who have severe haemoglobinopathies. The main objective of this study was to evaluate the results of allo-HSCT in paediatric patients with TM or SCD performed in paediatric hematopoietic transplant units within the Spanish Group of Bone Marrow Transplantation in Children (GETMON). Material and methodsRetrospective review of patients undergoing HSCT in the GETMON units until 2015. ResultsA total of 65 patients were analysed (43 patients were affected with TM and 22 with SCD), who received allo-HSCT in 6 GETMON units between November 1989 and December 2014. Event-free survival three years post-transplant was 81% and overall survival 92% in patients with TM. Event-free survival three years post-transplant was 79% and overall survival 85% in patients with SCD. ConclusionsThe results of this series are comparable to the results of other international series and offer a platform from which to continue trying to improve the evolution of these patients.

Reduced-intensity conditioning haematopoietic stem cell transplantation in genetic diseases: Experience of the Spanish Working Group for Bone Marrow Transplantation in Children

Reduced-intensity conditioning haematopoietic stem cell transplantation in genetic diseases: Experience of the Spanish Working Group for Bone Marrow Transplantation in Children

Rebound thymic hyperplasia after bone marrow transplantation in children with haemato-oncological diseases.

Aim of the studyTo evaluate prevalence of rebound thymic hyperplasia (RTH) after bone marrow transplantation (BMT) in paediatric patients with haemato-oncological diseases.Material and methodsBetween February 2013 and December 2017, BMT was performed in 189 paediatric patients with haemato-oncological diseases in our institution. Fifty-six patients who underwent at least two chest computed tomography (CT) exams performed before and after BMT were included in the study. Maximum transverse and anterior-posterior (AP) diameters and CT attenuation of the thymus were measured on axial images. Thymic enlargement was considered when both transverse and AP diameters increased. RTH was defined as the presence of thymic enlargement on CT after BMT relative to the CT taken before.ResultsTwenty of 56 patients (36%) demonstrated RTH (12 boys, 8 girls; age range = 4-18 years; median age = 9.8 years). In 20 patients with RTH, seven patients (35%) were diagnosed with ALL, five patients (25%) with thalassemia, two patients (10%) with AML, and one patient (5%) with various diseases. Mean follow-up period between pre-BMT CT and BMT was 46 days, which was 239 days between BMT and post-BMT CT. Mean thymic transverse and AP diameters were 9 mm and 16 mm, respectively, before BMT, which were 17 mm and 33 mm after BMT. Mean HU was 57 on contrast enhanced and 35 on unenhanced images before BMT, which were 59 and 36, respectively, after BMT.ConclusionsRTH is common finding after BMT in children with various haemato-oncological diseases and should be taken under consideration in paediatric patients after BMT.

Outcomes of matched sibling donor bone marrow transplantation in children using single-agent calcineurin inhibitors as prophylaxis for graft versus host disease.

Optimal graft versus host disease (GVHD) prophylaxis prevents severe manifestations without excess immunosuppression. Standard prophylaxis includes a calcineurin inhibitor (CNI) with low-dose methotrexate. However, single-agent CNI may be sufficient prophylaxis for a defined group of patients. Single-agent CNI has been used for GVHD prophylaxis for human leukocyte antigen (HLA)-matched sibling donor (MSD) bone marrow transplants (BMTs) in young patients at the Children's Hospital of Philadelphia for over 20 years. Here, we describe outcomes using this prophylactic strategy in a recent cohort. We performed a single-institution chart review and retrospective analysis of consecutive children undergoing MSD BMT who received single-agent CNI for GVHD prophylaxis between January 2002 and December 2014. Fifty-two children with a median age of 6.1 years (interquartile range [IQR] 2.5-8.3) and donor age of 6 years (IQR 3-10), with malignant and nonmalignant diseases (n = 35 and 17, respectively) were evaluated. Forty-three (82.6%) received oral prophylaxis with single-agent tacrolimus after initial intravenous therapy. Rates of GVHD were consistent with reported rates on dual prophylaxis: the overall incidence of grades 2-4 acute GVHD was 25.5%, grades 3-4 GVHD 9.8%, and chronic GVHD 10.4%. The cumulative incidence of relapse among children with malignancy was 20% at a median of 237 days (IQR 194-318) post-transplant. Two-year overall survival was 82.7% (95% confidence interval [CI]: 69.4-90.6%) and event-free survival was 78.9% (95% CI: 65.1-87.7%). No patient experienced graft failure. Single-agent CNI is a safe, effective approach to GVHD prophylaxis in young patients undergoing HLA-identical sibling BMT. Additionally, single-agent oral tacrolimus is a reasonable alternative to cyclosporine in this population.

Reduced-intensity conditioning haematopoietic stem cell transplantation in genetic diseases: Experience of the Spanish Working Group for Bone Marrow Transplantation in Children

Haematopoietic stem cell transplantation (HSCT) involves implanting cellular elements capable of generating a new and healthy haematopoietic system. Reduced intensity conditioning (RIC) consists of an immunosuppressive treatment to facilitate a progressive implant with lower morbidity. This type of conditioning can also lead to myelosuppression, which is potentially reversible over time. Reduced intensity conditioning enables HSCT to be performed on patients with genetic diseases for whom added comorbidity is undesirable due to the high doses of chemotherapy that accompanies conventional myeloablative regimens. An analysis was performed on the outcomes of 68 paediatric patients with genetic diseases who underwent HSCT with RIC between 2005 and 2013 in the of Paediatric Haematopoietic Stem Cell Transplantation Units that are part of the Spanish Working Group for Bone Marrow Transplantation in Children. A multicentre study was conducted including 68 patients, of whom 43 had Primary Immunodeficiency, 21 with congenital haematological diseases, and 4 with metabolic diseases. Fifty (73.5%) of the 68 patients were still alive. The Overall Survival (OS) at nine years was 0.74. Twenty-three (33.8%) had some event during the course of the HSCT, with an event-free survival rate of 0.66. The OS in patients with haematological diseases was 0.81, being 0.7 in primary immunodeficiencies, and 0.4 in metabolic diseases. No significant difference was observed between the 3 groups of diseases. As regards the source of haematopoietic progenitors, there was an OS rate of 0.74 in patients transplanted with peripheral blood, 0.70 with bone marrow, and 0.70 and with cord blood, with no statistically significant differences. Favourable results have been obtained in HSCT with reduced intensity conditioning in genetic diseases. It should be noted that the risks and benefits of the RIC in patients with metabolic diseases need to be assessed on an individual basis.

Immune and Hematological Reconstitution after Allogenic Bone Marrow Transplantation in Tunisian Pediatric Recipients: Prospective Study and Tunisian Experience Report

AIM: A regular monitoring of the immune reconstitution mainly based on the quantitative determination of lymphocyte T subpopulation. This is prospective analysis for 1 year in Tunisian children treated with allogenic intrafamilial bone marrow transplantation. Methods: We conducted a prospective analysis for 1 year follow up enrolling 25 children treated with allogenic intrafamilial bone marrow transplantation among them two cases of Peripheral hematopoietic transplantation and placental cord blood transplantation including: aplastic anemia (6 cases), hemoglobinopathies (12 cases), myelodysplastic syndrome (1 case), 2 cases of Acute lymphocytic leukemia, a case of congenital amegacarycytosis and 3 cases of primary immunodeficiency with lack of expression of major MHC class II. All subjects received different conditioning regimens according to the indication. Our study consisted of a regular monitoring of the immune reconstitution mainly based on the quantitative determination of lymphocyte T subpopulation. So, these tests were routinely requested to 1 month, 2 months, 3 months, 6 months, 9 months and 12 months post- bone marrow transplantation. Results: The average time of engraftment was 18 days corresponding to neutrophil recovery (12-24). For the T cell recovery, a rate of CD4 + T lymphocytes &gt; 200/ mm3 was provided within an average of 2.5 months (1-7). The average time to obtain CD8+ T lymphocytes &gt;200 /mm3 was 2 months (1-5). The humoral immune reconstitution was made within an average of 2 months (1-4). A ratio of CD4+ / CD8+ T lymphocytes (&gt;1) was obtained within 10 months and a half (1-24). Univaried analysis showed a significant correlation between the bone marrow sex matched and the faster reorganization of CD8 + T cells (p = 0.042). Moreover, a quantity of CD34 +&gt; 6x 106/ kg was significantly associated with the recapture of a formula lymphocyte T CD4+ / CD8+ (&gt; 1) (p=0.03). Conclusion: The immune recovery post bone marrow transplantation in children began with myeloid lineage then lymphoid B then lymphoid T. The inversion of the ratio CD4 +/CD8+ T lymphocytes, seemed to be influenced on the one hand by the high content of CD34 + cells in the graft as well as the type of conditioning on the other hand by the CMV infection since it accelerates significantly CD8+ T lymphocyte reconstitution.

51 - Increased Vitamin D Binding Protein Levels Are Associated with Improved Overall Survival Following Bone Marrow Transplant in Children

51 - Increased Vitamin D Binding Protein Levels Are Associated with Improved Overall Survival Following Bone Marrow Transplant in Children