Pediatric Bone Marrow Transplant Research Articles

Safety of Liposomal Cytarabine Prophylaxis in Pediatric Bone Marrow Transplant (BMT) Recipients with Acute Leukemia (AL) and Non Hodgkin Lymphoma (NHL) at High Risk of Cns Relapse

Abstract Abstract 4249 BACKGROUND: Liposomal Cytarabine is a derivative of cytarabine designed for intrathecal or intraomaya treatment of leukemia/lymphomatous meningitis (LLM). This formulation allows for sustained release with prolonged therapeutic concentration and drug exposure of 8 to 14 days in children and adults, respectively. Adult trials have shown liposomal cytarabine 50mg to be both safe and effective in the treatment of LLM (Glantz et al, JCO 1999). Bomgaars et al. investigated the use of liposomal cytarabine in children in a phase I dose escalation trial and demonstrated the maximal tolerated dose to be 35mg and that it was safe, well tolerated and effective (Bomgaars et al., JCO 2004). Comparisons of liposomal cytarabine use with conventional methotrexate prophylaxis suggest an improved quality adjusted survival benefit for patients where any possible additional toxicities are out measured by prolonged overall survival (Cole et al, Cancer 2003). However, there remains a paucity of data on the use of liposomal cytarabine prophylaxis to prevent LLM in pediatric patients, particularly in pediatric allogeneic stem cell (AlloSCT) recipients. Review of the literature reveals conflicting data concerning the efficacy of intrathecal chemoprophylaxis in children with leukemia/lymphoma after hematopoietic stem cell transplant. Recent multicenter trials suggest no statistically significant difference in the incidence of isolated or mixed CNS relapses between children receiving standard post-SCT intrathecal prophylaxis versus those that received no prophylaxis (Rubin et al., BMT 2011). This highlights the need to explore alternative chemoprophylaxis strategies in these high risk patients so that significant progress can be achieved. OBJECTIVE: We report on the safety and tolerability of liposomal cytarabine prior to and following allogeneic or autologous stem cell transplant in pediatric BMT recipients with AL and NHL. METHODS: Pediatric stem cell recipients with a history of AL or NHL and high risk of CNS disease received liposomal cytarabine 35mg ( 21yr) via lumbar puncture or omaya resevoir pre conditioning and approximately every 3months for 1–2yrs post stem cell transplant. No other intrathecal prophylaxis was administered. Patients received dexamethasone (0.15mg/kg/dose BID) concomitantly × 5days. Eight patients received a 9/10 or 10/10 matched unrelated donor transplant, 1 patient received an 8/10 matched unrelated donor. There were 9 matched related donor transplants and 3 autologous transplants. Twelve patients received a TBI (1200 cGy) based myeloablative conditioning regimen. Seven patients received an additional CNS boost of up to 1200 cGy during conditioning. All allogeneic SCT recipients received GVHD prophylaxis as previously described (Oswunko/Cairo, BBMT 2004; Bhatia et al, BBMT 2009) with tacrolimus and MMF. RESULTS: To date there have been 21 patients: (12 ALL, 2 AML, 3 Burkitt, 3 DLBCL and 1 T-LL). At the time of transplant, 7 patients were CR1/PR1, 10 patients CR2 and 4 patients CR3. Among all patients, they have received a total of 46 doses (median=1, range 1–12). Median age: 12yr (range 6–22). Mean follow up: 517 days (median= 294days). Eight of 21 patients had a history of CNS AL/NHL involvement prior to AlloSCT. No patients had evidence of LLM at the time of AlloSCT. Two patients experienced Grade II-III headache. Grade II-III vomiting was also noted in 2 additional patients. Head CT scans that were done at the time of symptom occurrence were negative for any evidence of hydrocephalus, hemorrhage, infarct or inflammation in all patients. Patients were treated with supportive therapy and had complete resolution of symptoms. Seven patients developed relapsed systemic disease, but none relapsed in the CNS. An additional 3 patients are deceased secondary to multi organ failure and 2 patients from overwhelming infection. However, none of the above patients had CNS AL/NHL at time of death. CONCLUSION: These preliminary results suggest that prophylactic liposomal cytarabine is tolerable and effective in pediatric AlloSCT and AutoSCT recipients at risk for CNS relapse. Larger studies are needed in the future to compare this to other CNS prophylaxis regimens post auto or AlloSCT. In addition, trials are in development to investigate the combination of intraomaya Rituximab followed by liposomal Cytarabine in children with recurrent/refractory CNS CD20+ AL/NHL. Disclosures: No relevant conflicts of interest to declare.

High Dose Methylprednisolone for Veno-Occlusive Disease of the Liver in Pediatric Bone Marrow Transplant Recipients

High Dose Methylprednisolone for Veno-Occlusive Disease of the Liver in Pediatric Bone Marrow Transplant Recipients

Estimated additional lifetime risk of cancer attributable to diagnostic CT in a pediatric bone marrow transplant cohort: Experience at a single academic institution

Purpose: To determine the frequency of CT procedures in a cohort of bone marrow transplant patients and estimate the effective dose from each CT procedure as well as rough estimates of lifetime attributable risk (LAR) of cancer (both incidence and mortality). Background: Pediatric patients who undergo bone marrow transplant benefit greatly from the diagnostic power of computed tomography, but due to the need for frequent imaging, these patients are repeatedly exposed to the carcinogenic potential of ionizing radiation. Methods: CT Imaging and patient parameters were collected from a retrospective cohort of bone marrow transplant patients. Dosimetry was estimated as a function of age, dose length product (DLP), and scan region based on published DLP to effective dose tables. Lifetime attributable risk (LAR) of cancer as a function of age, gender, and organ specific dose was derived from BEIR VII phase 2 estimates. Results: 44 patients with bone marrow transplant were included and ranged in age from 7 months to 20 years (average age, 9 years). The average number of CT studies per patient was 3.2 over the 15 month period. The average effective dose for each study was 5.9 +/– 4.5 mSv. Cumulative effective dose to each patient was 20 +/– 32 mSv. It was estimated that in this cohort, the CT imaging performed over a 15-month period on a 64-slice scanner led to a lifetime additional risk of cancer incidence of 5 in 1000 and a lifetime additional risk of cancer mortality of 2 in 1000. Conclusion: Diagnostic CT is important in the assessment and management of ill patients following bone marrow transplant. The risk of ionizing radiation leading to additional development of cancer merits using as low a CT technique as reasonable to achieve a diagnostic study.

Safety of Liposomal Cytarabine Prophylaxis in Pediatric Bone Marrow Transplant (BMT) Recipients with Acute Leukemia (AL) and Non Hodgkin Lymphoma (NHL) At High Risk of CNS Relapse

Abstract 4249 BACKGROUND:Liposomal Cytarabine is a derivative of cytarabine designed for intrathecal or intraomaya treatment of leukemia/lymphomatous meningitis (LLM). This formulation allows for sustained release with prolonged therapeutic concentration and drug exposure of 8 to 14 days in children and adults, respectively. Adult trials have shown liposomal cytarabine 50mg to be both safe and effective in the treatment of LLM (Glantz et al, JCO 1999). Bomgaars et al. investigated the use of liposomal cytarabine in children in a phase I dose escalation trial and demonstrated the maximal tolerated dose to be 35mg and that it was safe, well tolerated and effective (Bomgaars et al., JCO 2004). Comparisons of liposomal cytarabine use with conventional methotrexate prophylaxis suggest an improved quality adjusted survival benefit for patients where any possible additional toxicities are out measured by prolonged overall survival (Cole et al, Cancer 2003). However, there remains a paucity of data on the use of liposomal cytarabine prophylaxis to prevent LLM in pediatric patients, particularly in pediatric allogeneic stem cell (AlloSCT) recipients. Review of the literature reveals conflicting data concerning the efficacy of intrathecal chemoprophylaxis in children with leukemia/lymphoma after hematopoietic stem cell transplant. Recent multicenter trials suggest no statistically significant difference in the incidence of isolated or mixed CNS relapses between children receiving standard post-SCT intrathecal prophylaxis versus those that received no prophylaxis (Rubin et al., BMT 2011). This highlights the need to explore alternative chemoprophylaxis strategies in these high risk patients so that significant progress can be achieved. OBJECTIVE:We report on the safety and tolerability of liposomal cytarabine prior to and following allogeneic or autologous stem cell transplant in pediatric BMT recipients with AL and NHL. METHODS:Pediatric stem cell recipients with a history of AL or NHL and high risk of CNS disease received liposomal cytarabine 35mg (<21yr) or 50mg (>21yr) via lumbar puncture or omaya resevoir pre conditioning and approximately every 3months for 1–2yrs post stem cell transplant. No other intrathecal prophylaxis was administered. Patients received dexamethasone (0.15mg/kg/dose BID) concomitantly × 5days. Eight patients received a 9/10 or 10/10 matched unrelated donor transplant, 1 patient received an 8/10 matched unrelated donor. There were 9 matched related donor transplants and 3 autologous transplants. Twelve patients received a TBI (1200 cGy) based myeloablative conditioning regimen. Seven patients received an additional CNS boost of up to 1200 cGy during conditioning. All allogeneic SCT recipients received GVHD prophylaxis as previously described (Oswunko/Cairo, BBMT 2004; Bhatia et al, BBMT 2009) with tacrolimus and MMF. RESULTS:To date there have been 21 patients: (12 ALL, 2 AML, 3 Burkitt, 3 DLBCL and 1 T-LL). At the time of transplant, 7 patients were CR1/PR1, 10 patients CR2 and 4 patients CR3. Among all patients, they have received a total of 46 doses (median=1, range 1–12). Median age: 12yr (range 6–22). Mean follow up: 517 days (median= 294days). Eight of 21 patients had a history of CNS AL/NHL involvement prior to AlloSCT. No patients had evidence of LLM at the time of AlloSCT. Two patients experienced Grade II-III headache. Grade II-III vomiting was also noted in 2 additional patients. Head CT scans that were done at the time of symptom occurrence were negative for any evidence of hydrocephalus, hemorrhage, infarct or inflammation in all patients. Patients were treated with supportive therapy and had complete resolution of symptoms. Seven patients developed relapsed systemic disease, but none relapsed in the CNS. An additional 3 patients are deceased secondary to multi organ failure and 2 patients from overwhelming infection. However, none of the above patients had CNS AL/NHL at time of death. CONCLUSION:These preliminary results suggest that prophylactic liposomal cytarabine is tolerable and effective in pediatric AlloSCT and AutoSCT recipients at risk for CNS relapse. Larger studies are needed in the future to compare this to other CNS prophylaxis regimens post auto or AlloSCT. In addition, trials are in development to investigate the combination of intraomaya Rituximab followed by liposomal Cytarabine in children with recurrent/refractory CNS CD20+ AL/NHL. Disclosures:No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Patients with Treatment-Related Myelodysplastic Syndrome or Acute Myelogenous Leukemia

The development of treatment-related myelodysplastic syndrome (tMDS) or treatment-related acute myelogenous leukemia (tAML) is a complication that can occur after chemotherapy or radiation therapy. Eighteen patients with a previous malignancy treated at our institution and three patients with a nonmalignant primary tumor received an allogeneic hematopoietic stem cell transplant (HSCT) on the pediatric bone marrow (BM) transplantation service for the treatment of tMDS/tAML over a 15-year period. Five patients proceeded to HSCT without induction chemotherapy. Fourteen patients received high-dose cytarabine according to the Capizzi II regimen as first-line induction therapy with 13 of them achieving complete remission (CR) or refractory anemia (RA) with persistent cytogenetic abnormalities after this treatment. Two patients received an anthracycline-based induction therapy. Conditioning regimens were selected according to previous therapies: 11 patients received busulfan-melphalan-fludarabine (BU-MEL-FLU), which consisted of busulfan (0.8 mg/kg/dose every 6 hours ×10 doses), melphalan (70 mg/m(2)/dose × two doses), and fludarabine (25 mg/m(2)/dose × five doses) for cytoreduction; three patients received a total body irradiation (TBI)-containing regimen; seven patients received myeloablative regimens containing busulfan and/or melphalan and/or thiotepa with doses modified for organ toxicity. Sixteen patients received T cell-depleted (TCD) grafts; four patients received unmodified grafts; one patient received a double-unit cord blood transplantation (DUCBT). Donors included HLA-matched (n = 9), or mismatched (n = 3) related donors, or HLA-matched (n = 4), or mismatched (n = 4) unrelated donors, or DUCBT (n = 1). Disease status at the time of HSCT was: morphologic and cytogenetic CR (n = 12); RA with positive cytogenetics (n = 6); and refractory disease (n = 3). With a median follow-up of 5.9 years (2.2-15.7 years), the 5-year overall survival (OS) and disease-free survival (DFS) rates for the entire group were 61.1% with 12 patients alive without evidence of either primary disease or tMDS/tAML. The OS and DFS rate for the 11 patients who received the BU-MEL-FLU cytoreduction with TCD grafts was 54.5%. DFS was 65.7% for patients in RA or CR at HSCT compared with 0% for patients with >5% residual marrow blasts (P = .015). Nine patients died; the cause of death was relapse of MDS/AML (n = 4) or primary disease (n = 2), graft-versus-host disease (GVHD; n = 2), and infection (n = 1). Four patients developed grade II to IV acute GVHD. One patient developed localized chronic GVHD. Our results suggest that the strategy of induction with high-dose cytarabine therapy followed by allogeneic stem cell transplantation improves the overall outcome for patients with tMDS/tAML. In addition, the use of a TCD transplantation with BU-MEL-FLU as cytoreduction may decrease the toxicity of transplantation in heavily pretreated patients without an increase in relapse rate.

Safety and Efficacy of CMX001 as Salvage Therapy for Severe Adenovirus Infections in Immunocompromised Patients

No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥ 4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/μL (range, 7-1500 cells/μL). Eight patients (61.5%) had a ≥ 1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.

Relationship between clinical sinusitis symptoms and sinus CT severity in pediatric post bone marrow transplant and immunocompetent patients

Since typical inflammatory responses may be diminished in children following bone marrow transplant (BMT), computed tomography (CT) imaging of the sinuses has been increasingly ordered to diagnose sinusitis in this group. The objective of this study was to determine the association between clinical sinusitis symptoms and sinus opacification on CT scans in post BMT versus immunocompetent children. Our sample was comprised of 64 post BMT and 86 immunocompetent children with sinus CT scans. CT sinus opacification was scored using the modified Lund-Mackay staging system. The relationship between clinical sinusitis symptoms (rhinorrhea, nasal congestion, cough, headache, and facial pain) and opacification was compared for the two groups. The severity of sinus opacification in the BMT group was significantly higher compared to the immunocompetent group. In combined patient groups the odds ratio (OR) for moderate/severe sinusitis was significantly elevated for rhinorrhea (OR = 3.00; 95% confidence interval [CI], 1.27-7.12), cough (OR = 2.80; 95% CI, 1.22-6.42), and having either rhinorrhea, nasal congestion, or cough (OR = 4.76; 95% CI, 1.71-13.24). While the immunocompetent group had a greater number of sinusitis symptoms compared to the post BMT group, both groups had a significant increase in the severity on CT with increasing number of symptoms. In post BMT patients, our data demonstrated higher odds of moderate/severe sinusitis on CT scans associated with rhinorrhea, cough or nasal congestion. These finding suggest that in post BMT children, detailed sinus history may still play a vital role in the diagnosis of sinusitis.

Comparing Administration of Nutrition Support With Prescribed Dose

The aim of this study was to evaluate whether pediatric bone marrow transplant (BMT) patients receive the prescribed dose of nutrition support (NS). Data were obtained from electronic and paper charts at St. Jude Children's Research Hospital. The amount of NS received was compared with the amount prescribed. Data were collected on 32 patients for 63 hospital stays in which NS was administered. The mean percentage of nutrition prescription met and percentage of total estimated energy met were 69% and 72%, respectively. Allogeneic BMT patients received significantly more of their nutrition prescription (92%) than autologous BMT patients did (54%, P < .01). Malnourished patients were significantly more likely to receive the full dose of NS than patients who were considered nourished or obese (P < .05). This study showed that patients who were most in need of NS were more likely to receive the full dose.

Is the NBN Gene Mutation I171V a Potential Risk Factor for Malignant Solid Tumors in Children?

NBN gene is considered as one of the low-to-moderate cancer susceptibility gene. At least 4 germline NBN mutations have been found in several malignancies in adults. In our studies, we observed the high incidence of germline mutation I171V of NBN gene in breast, colorectal, larynx cancer, and in multiple primary tumors. In this study, we would like to answer the question whether I171V germline mutation of NBN gene may constitute risk factor for solid tumors in children. The frequency of this mutation has been analyzed in patients with neuroblastoma (n=66), Wilms tumor (n=54), medulloblastoma (n=57), and rhabdomyosarcoma (n=82) hospitalized in Pediatric Oncology, Hematology and Bone Marrow Transplantation Department in the years between 1987 and 2010. About 2947 anonymous blood samples collected on Guthrie cards drawn from the newborn screening program of the Wielkopolska region have been used as controls. All the patients and controls came from the same geographical region. I171V mutation of the NBN gene has been observed in 5 controls. Among children with solid tumors only in 1 child with medulloblastoma I171V variant has been found. In conclusion, I171V germline mutation in contrary to adults cannot be considered as a risk factor for children malignancies. However, owing to low number of patients with solid tumors the possibility of a Type II error may exist.

Treatment of relapsed acute lymphoblastic leukemia: Approaches used by pediatric oncologists and bone marrow transplant physicians

Management of relapsed B-precursor acute lymphoblastic leukemia (ALL) is challenging and varied. We hypothesized that treatment approaches differ between pediatric oncologists and bone marrow transplant (BMT) physicians. A survey addressing management of relapsed ALL was sent to pediatric oncologists (n = 883) and BMT (n = 86) physicians across North America. A number of similarities in treatment approaches were identified including: choice of chemotherapy for re-induction/consolidation, preference for unrelated donors (URDs) in very early marrow relapse and the choice to not use URD donors in late marrow relapse. However, differences between the two disciplines were noted. For patients who relapsed 18-36 months from diagnosis, the majority of oncologists (53.7%) would retreat with chemotherapy while a majority BMT physicians (70.3%) recommended URD transplant (P < 0.001). Oncologists were also less likely to use minimal residual disease (MRD) in relapse assessment compared to BMT physicians (52% vs. 67.2%; P = 0.028) and more oncologists believed MRD testing was experimental and/or not proven in relapsed ALL (27.1% vs. 12.3%; P = 0.011). This study highlights management differences in children with ALL between pediatric oncologists and BMT physicians, identifying opportunities for collaborative clinical trials.

Endocrine Complications Following Pediatric Bone Marrow Transplantation

Pediatric bone marrow transplantation (BMT) for various diseases can lead to endocrine system dysfunction owing to preparative regimens involving chemotherapy and radiation therapy. We assessed the prevalence of post-BMT endocrine complications in children treated at the Alberta Children's Hospital (ACH) from 1991 to 2001. Time of onset of endocrine dysfunction, underlying disease processes, chemotherapy, radiation therapy and age at BMT were characterized. Subjects of <18 years of age at the time of allogeneic or autologous BMT for whom 1-year follow-up through the ACH and a chart were available for review were included in the study. Subjects with a pre-existing endocrine condition were excluded. Of the 194 pediatric BMT procedures performed at the ACH between January 1, 1991 and December 31, 2001, 150 complete charts were available for review. Sixty five subjects received follow-up care at other centers and were excluded. Therefore, a total of 85 subjects were included in the review. The prevalence of endocrine complications identified was: primary hypothyroidism 1.2%, compensated hypothyroidism 7.0%, hyperthyroidism 2.4%, hypergonadotrophic hypogonadism 22.4%, abnormal bone density 2.4%, and secondary diabetes mellitus 1.2%. These findings emphasize the need to screen for endocrine system dysfunction, particularly hypergonadotrophic hypogonadism, in children who have undergone BMT. Children need long-term follow-up so that endocrine complications can be diagnosed and treated promptly.

The Pain Paradigm – Practice Divide: Understanding the Gap Between Current Pain Concepts and Clinical Practice in Pediatric Bone Marrow Transplantation

The Pain Paradigm – Practice Divide: Understanding the Gap Between Current Pain Concepts and Clinical Practice in Pediatric Bone Marrow Transplantation

Optimization of Anti-Thymocyte Globulin Exposure in Paediatric Bone Marrow Transplantation in Order to Design an individualized Dosing Regimen

Optimization of Anti-Thymocyte Globulin Exposure in Paediatric Bone Marrow Transplantation in Order to Design an individualized Dosing Regimen

KL-6 as a Marker for Bronchiolitis Obliterans in Pediatric and Young Adult Bone Marrow Transplant Patients

Bronchiolitis obliterans syndrome (BOS) is a serious complication of allogeneic bone marrow transplant (BMT). There is a need for a non-invasive diagnostic test in order to detect BOS in transplant recipients. KL-6 is a high molecular weight glycoprotein classified as MUC1 mucin that is expressed on the epithelial surface of type II alveolar cells in the lungs and is present on the surface of bronchiolar epithelial cells. KL-6 is an active chemotactic factor for fibroblasts which could play a role in the early pathogenesis of BOS. We hypothesize that serum KL-6 levels will be elevated in subjects with known BOS. This is a case control study that employs convenience sampling for KL-6 samples. It is a multi-center study. Serum samples were obtained from 15 subjects that underwent allogeneic BMT and 20 healthy controls between the ages of 6 months and 30 years. Of the 15 subjects that underwent BMT, 3 met the criteria for BOS. The definition of BOS was based upon pulmonary function tests (a sustained drop in FEV1 of 20% from pre-transplantation baseline) or biopsy. KL-6 levels were determined using a commercially available sandwich-type enzyme linked immunosorbent assay kit. Mean serum KL-6 levels +/− standard deviation for BMT subjects with BOS, BMT subjects without BOS and healthy controls were 571.6 +/−350.5, 302.3 +/−87.3 and 209.1 +/−77.6 U/ml, respectively. The difference between BMT subjects with BOS and those without BOS was statistically significant (p = 0.003) as well as those with BOS and healthy controls (p = 0.001). There was no statistical difference between BMT subjects without BOS and healthy controls (p = .956). KL-6 levels were significantly elevated in BMT subjects with BOS as compared those without BOS and healthy controls. KL-6 could serve as a diagnostic tool in detecting BOS in BMT recipients.

BK-Virus Associated Hemorrhagic Cystitis in Children Following Haematopoietic Stem Cell Transplantation. A Six Years Experience in One Pediatric Bone Marrow Transplantation Center

Hemorrhagic cystitis (HC) is a common complication after haematopoietic stem cell transplantation (HSCT). Urotropic viruses may cause late-onset HC (BK virus {BKV}, adenovirus, CMV) associated with severe immunosuppression. Treatment is mainly symptomatic. The incidence and severity of HC depends on primary disease, pre-transplant viral status, conditioning, immunosuppressive drugs, source of graft and Graft-versus-Host Disease.

The Power of Process Improvement Methodology on a Highly Complex Pediatric Bone Marrow Transplant Unit's Catheter Associated Blood Stream Infection Rates

Cincinnati Children's Hospital Medical Center (CCHMC) has instituted a major safety initiative to reduce central venous catheter (CVC) blood stream infections (BSI). A multidisciplinary approach utilizing quality improvement methodology was implemented initially in the PICU, leading to the development of a CVC maintenance bundle.

Endocrine complications following pediatric bone marrow transplantation

Pediatric bone marrow transplantation (BMT) for various diseases can lead to endocrine system dysfunction owing to preparative regimens involving chemotherapy and radiation therapy. We assessed the prevalence of post-BMT endocrine complications in children treated at the Alberta Children's Hospital (ACH) from 1991 to 2001. Time of onset of endocrine dysfunction, underlying disease processes, chemotherapy, radiation therapy and age at BMT were characterized. Subjects of <18 years of age at the time of allogeneic or autologous BMT for whom 1-year follow-up through the ACH and a chart were available for review were included in the study. Subjects with a pre-existing endocrine condition were excluded. Of the 194 pediatric BMT procedures performed at the ACH between January 1, 1991 and December 31, 2001, 150 complete charts were available for review. Sixty five subjects received follow-up care at other centers and were excluded. Therefore, a total of 85 subjects were included in the review. The prevalence of endocrine complications identified was: primary hypothyroidism 1.2%, compensated hypothyroidism 7.0%, hyperthyroidism 2.4%, hypergonadotrophic hypogonadism 22.4%, abnormal bone density 2.4%, and secondary diabetes mellitus 1.2%. These findings emphasize the need to screen for endocrine system dysfunction, particularly hypergonadotrophic hypogonadism, in children who have undergone BMT. Children need long-term follow-up so that endocrine complications can be diagnosed and treated promptly.

Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors

Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors

Brazilian Society of Pediatric Oncology - SOBOPE

The history of pediatric oncology in Brazil is strongly linked to the history of the Sociedade Brasileira de Oncologia Pediatrica (SOBOPE). In the seventies two of our most prestigious pediatric oncologists, Waldir Veiga Pereira and Vicente Odone Filho, decided to go to Memphis, USA to learn about the most recent advances in pediatric hematology and Oncology. It was there they met Rhomes Joao Amim Aur. Rhomes Aur is a pioneer in pediatric hematology and oncology; the most important award in Brazilian pediatric oncology is named after him. Saint Jude Children's Hospital has a strong connection with Brazil. Since he moved to Memphis, Raul Ribeiro has continuously provided opportunities by helping Brazilian pediatric oncologists and institutions. Silvia Brandalise also visited Dr. Odone in Saint Jude. There they talked about acute lymphoblastic leukemia and a few years later in 1980, she met Milton Ruiz, Celso Carlos Campos Guerra and Rhomes Aur in Santos to discuss the first Brazilian protocol for acute lymphoblastic leukemia. The Brazilian society of pediatric oncology was founded in 1981 by a group of physicians led by Virgilio Carvalho Pinto. The founders were committed to change the dismal prognosis of children and adolescents with cancer. At that time diagnosis was practically a death sentence; few hospitals could offer a proper treatment. At the same time Beatriz de Camargo started the Wilms' tumor study group.(1) Alois Bianchi, the first head of the Pediatric Oncology Department at the A C Camargo Hospital, was the second president of SOBOPE. With Nubia Mendonca, one of the founders and most active pediatric oncologists in Brazil, the meetings of SOBOPE became routine. She officially established the Brazilian cooperative groups. After Nubia, Waldir Pereira, Silvia Brandalise, Fernando Werneck and Jose Roberto Resende contributed to the growth of SOBOPE making it a more prestigious Society. Ten years ago, with effort of one of our former presidents, Sidnei Epelman, SOBOPE started a data management center, a Computerized Data Center. This center and the cooperative groups continued to develop with Sonia Vianna. Renato Melaragno, another former President, created a strong partnership with the Instituto Ronald Mc Donald. All these collaborative studies resulted in National and International publications. The osteosarcoma study by Dr Petrilli demonstrated the Brazilian reality as opposed to the reality of other countries in respect to the size of tumors and metastasis.(2) The Ewing Sarcoma Study, led by Brunetto(3) highlighted a new combination of drugs. More recent projects are using an efficient on-line data collection system. With this quicker and more efficient system, data analysis will correct protocols in relation to toxicity. The Ewing Sarcoma protocol, like the osteosarcoma study, was developed in partnership with GALOP (the Latin American Group of Pediatric Oncology), showing that it is possible to work in harmony with other countries. The last Brazilian study of acute lymphoblastic leukemia showed new maintenance therapy.(4) The cooperative group of germ cell tumors by Luiz Fernando Lopes also published their results;(5) This group has a strong partnership with other international institutions that present data at international meetings. The Brazilian Committee of Pediatric Bone Marrow Transplantation, in a joint effort between SOBOPE and theSociedade Brasileira de Transplante de Medula Ossea (SBTMO), also published a consensus.(6) This consensus, organized by the SBTMO, was developed not only with international data, but with our local experience and publications. We cannot forget Celia Gianotti, who is internationally recognized because of her important work with the campaign for early diagnosis of retinoblastoma in Brazil.(7,8) The National Cancer Institute is making every effort to know about the reality of pediatric cancer in Brazil.(9) We should not need to use data from other countries to infer the situation here in Brazil; a few years ago, we had no idea about the numbers of new cases. SOBOPE is happy about this opportunity to join the Revista Brasileira de Hematologia e Hemoterapia (RBHH). We are very thankful to ABHH who kindly opened this door to us. This partnership will certainly further improve the quality of the RBHH. It is important to remember that the RBHH is the only scientific journal in the area of hematology in the southern hemisphere. SOBOPE is now one of the few societies of pediatric oncology that has the honor of participating in an official journal.

The role of cytomegalovirus infection and disease in pediatric bone marrow transplant recipients in Mexico City in the context of viral drug resistance

We aimed to identify those pediatric patients undergoing ABMT with CMV EOD who developed GCV resistance. Forty-seven patients were analyzed following ABMT. Prospective post-transplant CMV monitoring was performed weekly for the detection of viral leukocyte DNAaemia, viral plasma DNAaemia, and viral DNAuria by PCR. Plasma DNAaemia was confirmed from whole blood by the detection of CMV pp67 late mRNA using NASBA technology. In the cases of persistence of viral DNA in plasma, and positive viral RNA detection in blood, CMV drug resistance screening by comprehensive PCR-based RFLP and sequencing of the viral UL97 gene were performed retrospectively. Thirty of the 47 (63.82%) patients showed active CMV infection with 27/30 (74.4%) patients belonging to the D+R+ group and 25/30 with proven viral replication. In total, 2/30 (6.6%) children developed CMV pneumonia proven by immunohistochemistry. Screening of the viral UL97 gene revealed in one of these two cases (1/30, 3.3%) the simultaneous presence of two point mutations in codon 460 (M460V, M460I) conferring GCV resistance. The CMV seroprevalence (81%) and the incidence of active infection (63.8%) in Mexican children undergoing ABMT are very high.