Biomedical subjects

Carlos Rodriguez-Galindo

Publications and source records attributed to Carlos Rodriguez-Galindo.

At least 37 records · Page 2Linked to original sources

PubMed2005

Preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil, and leucovorin for pediatric nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is rare in children, accounting for <1% of all cases. Treatment most commonly includes radiotherapy but long-term side effects of such treatment can produce devastating cosmetic and functional sequelae in children. Chemotherapy may help to decrease the radiotherapy dose and limit the side effects of local therapies. However, little is known regarding the chemosensitivity of NPC tumors in pediatric patients. METHODS: Patients with American Joint Committee on Cancer (AJCC) Stage I/II disease (Stratum 01) received irradiation only. Patients with AJCC Stage III/IV disease (Stratum 02) received 4 courses of preradiation chemotherapy comprising methotrexate (120 mg/m2) on Day 1, with cisplatin (100 mg/m2) 24 hours later, 5-fluorouracil 1000 mg/m2 per day as a continuous infusion for 3 days, and leucovorin 25 mg/m2 every 6 hours for 6 doses. Irradiation was given after chemotherapy and consisted of 50.4 gray (Gy) to the upper neck and 45.0 Gy to the lower neck, with a boost to the primary tumor and positive lymph nodes for a total dose of 61.2 Gy. RESULTS: One patient was enrolled in Stratum 01 and 16 evaluable patients were enrolled in Stratum 02. The median age of the patients was 13 years and 65% of the patients were black. All patients tested had evidence of Epstein-Barr virus infection. Two-thirds of the patients developed Grade 3-4 mucositis during chemotherapy. The overall response rate to induction chemotherapy was 93.7%. The overall 4-year event-free and overall survival rates (+/- the standard error) were 77%+/-12% and 75%+/-12%, respectively. CONCLUSIONS: The current study demonstrated that childhood NPC was sensitive to chemotherapy and that chemotherapy before irradiation was feasible. Future trials should investigate equivalent efficacy with a reduced radiotherapy dose.

Adolescent↗

PubMed2005

Granulocyte-macrophage colony stimulating factor and immunosuppression in the treatment of pediatric acquired severe aplastic anemia.

BACKGROUND: Immunosuppressive therapy (IS) is effective in the treatment of patients with acquired severe aplastic anemia (SAA). An enhanced myeloid response and decreased infection risk may be possible with the addition of a hematopoietic cytokine. Published data on the combination of cytokines and IS in patients with SAA are limited. The addition of G-CSF to IS shortens the time to neutrophil count recovery, but may not improve overall survival. Because GM-CSF acts differently than G-CSF, its use in combination with IS may be different. PROCEDURE: A retrospective chart review was performed on patients diagnosed with SAA and treated with IS and GM-CSF at St. Jude Children's Research Hospital. Hematologic recovery, prognostic factors, and infection data were collected. RESULTS: Eighteen patients were included in this study. The median age at diagnosis was 7.2 years (range 1.8-17.0). Ten patients (56%) had a complete response, four (22%) a partial response, and four (22%) no response. Median time to erythrocyte and platelet transfusion independence were 90 (18,243) and 64 days (18-243), and to discontinuation of treatment 287 days (90-730). Median time to partial (ANC > 500) and full (ANC > 1,500) neutrophil recovery were 41 and 51 days, respectively. Seventeen documented discrete infections occurred in six patients over 36 patient years. CONCLUSIONS: GM-CSF, in addition to IS, may shorten time to neutrophil count recovery, may be beneficial in decreasing infection rates, and may improve platelet response in patients with SAA. However, consistent with studies utilizing G-CSF, GM-CSF probably does not affect overall response rate. To fully answer whether or not cytokine therapy is of added value to IS in pediatric patients, a multi-institutional randomized trial is needed.

Adolescent↗

PubMed2005

Biology, clinical characteristics, and management of adrenocortical tumors in children.

Childhood adrenocortical tumors (ACT) are very aggressive endocrine neoplasms whose incidence is quite low. Little is known about their pathogenesis, clinical presentation, and optimal treatment. In recent years, however, new information has been derived from the International Pediatric Adrenocortical Tumor Registry (IPACTR), and new clues to its pathogenesis have emerged. To provide an overview of the available data that may apply to pediatric ACT, we reviewed the epidemiology, pathogenesis, and treatment of ACT in adults and in children. Germline TP53 mutation is almost always the predisposing factor in childhood ACT. A unique germline mutation (TP53-R337H) has been described in Southern Brazil, where the incidence of ACT is 10-15 times the general incidence. Childhood ACT typically present during the first 5 years of life and has female predominance. Hormone hyperproduction is almost universal, and most patients present with virilization. Two-thirds of patients have resectable tumors. Surgery is the definitive treatment for ACT, and a curative complete resection should always be attempted. Cisplatin-based chemotherapy with mitotane is indicated for unresectable or metastatic disease, although its impact on overall outcome is slight. In childhood ACT, age, tumor size, and tumor resectability are the most important prognostic indicators. Outcome is stage-dependent; patients with small, resectable tumors have survival rates in excess of 80%, whereas the outcome for patients with unresectable disease is dismal. Patients with large, resectable tumors have an intermediate outcome. Childhood ACT are rare, but their unique epidemiology appear to implicate novel oncogenic pathways that are unique to the pediatric population. Multi-institutional and prospective studies are necessary to further our understanding of the pathogenesis and to improve outcomes.

Adolescent↗

PubMed2005

Effect on ocular survival of adding early intensive focal treatments to a two-drug chemotherapy regimen in patients with retinoblastoma.

PURPOSE: To evaluate vincristine and carboplatin with intensive focal treatments in the management of intraocular retinoblastoma. DESIGN: Noncomparative, retrospective interventional case series. METHODS SETTING: Institutional. PATIENT POPULATION: Sixteen patients (11 bilateral, 5 unilateral) with intraocular retinoblastoma. Interventional procedures: Patients were treated with eight courses of vincristine and carboplatin. Intensive focal treatments were administered after two courses of chemotherapy. MAIN OUTCOME MEASURES: Avoidance of external beam radiotherapy (EBRT) and eye survival. RESULTS: Twenty eyes (74.1%) were classified as Reese-Ellsworth Group V. All eyes responded to chemotherapy. With a median follow-up of 23 months (range 10 to 33 months) and a median of 5.5 focal treatments per eye (range 0 to 19 treatments), ocular survival was 81%. Eight eyes (30%) in five patients received EBRT. CONCLUSIONS: Vincristine and carboplatin combined with intensive focal treatments is an effective regimen for patients with intraocular retinoblastoma. This treatment regimen has outcomes comparable to those of more toxic regimens and merits further evaluation.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Pyogenic hepatic abscess after percutaneous liver biopsy in a patient with sickle cell disease.

Liver abscess is a rare complication of liver biopsy but has not been reported in a patient with sickle cell disease (SCD) undergoing this procedure. The authors report the case of a child with SCD, on treatment with chronic transfusions and desferrioxamine, who developed a delayed liver abscess after a liver biopsy in which Avitene, a topical hemostatic agent, was used. This is the first description of a liver abscess as a possible complication of liver biopsy in a child with SCD. The presence of a hepatic abscess should be considered in the differential diagnosis of atypical abdominal pain in patients with SCD.

Abdominal Pain↗

PubMed2004

Definitive irradiation in multidisciplinary management of localized Ewing sarcoma family of tumors in pediatric patients: outcome and prognostic factors.

PURPOSE: To assess the effect of radiation dose on local tumor control of the Ewing sarcoma family of tumors in 79 patients with localized disease treated at a single institution. METHODS AND MATERIALS: Thirty-seven patients received vincristine, actinomycin D, cyclophosphamide, and doxorubicin, and 42 received vincristine, actinomycin D, and cyclophosphamide, with alternating cycles of ifosfamide and etoposide; all underwent definitive radiotherapy (median dose, 37.5 Gy) with either low-dose (<40 Gy) or standard dose (> or =40 Gy) radiation delivered according to the protocol. We calculated the cumulative incidence of local treatment failure, disease recurrence, and overall survival and analyzed the effect of known prognostic factors and radiation dose. RESULTS: The cumulative incidence of local treatment failure at 10 years was 30.4% and that of disease recurrence was 40%. The overall survival rate was 64.5%. Patient age > or =14 years and tumor size > or =8 cm were adverse prognostic factors for local treatment failure; patient age > or =14 years was also associated with worse survival. Although the radiation dose alone did not predict for local treatment failure, the cumulative incidence of local failure at 10 years was 19% when tumors <8 cm were treated with <40 Gy, and no patient treated with standard doses (> or =40 Gy) developed local recurrence (p = 0.084). CONCLUSION: Tumor size and patient age predict for local tumor control in patients with Ewing sarcoma family of tumors treated with systemic therapy and definitive radiotherapy. Patients treated with reduced-dose radiotherapy experienced unacceptably high rates of local recurrence.

Adolescent↗

PubMed2004

Outcome after local recurrence of osteosarcoma: the St. Jude Children's Research Hospital experience (1970-2000).

BACKGROUND: Despite improvements in therapy for osteosarcoma, approximately 4-10% of patients experience a local recurrence and have a poor prognosis. METHODS: The authors analyzed prognostic factors for survival in 26 patients with a local recurrence of osteosarcoma who were treated between 1970 and 2000. RESULTS: The initial surgical procedure was amputation in 20 patients (76.9%) and limb salvage in 6 patients (23.1%). The median time from the diagnosis of osteosarcoma to local recurrence was 1.2 years (range, 1.2 months-6.1 years). Eleven patients (42.3%) developed an isolated local recurrence and 15 patients (57.7%) developed local and distant recurrence. The 5-year estimate of postrecurrence survival (PRS) (+/- 1 standard error) for the 26 patients was 19.2% +/- 7.7%. Recurrence > or = 2 years from the time of diagnosis was found to predict a better outcome (5-year PRS of 50.0% +/- 20.4%) compared with earlier recurrence (10.0% +/- 5.5%) (P = 0.037). Patients with negative margins after initial surgery were found to have improved survival (5-year PRS of 33.3% +/- 13.6%) compared with patients with positive margins (7.1% +/- 4.9%) (P = 0.015). Patients who underwent complete surgical resection at the time of recurrence were found to have a better PRS (5-year PRS of 41.7% +/- 14.2%) compared with patients who did not undergo surgery (0% +/- 0%) (P < 0.001). CONCLUSIONS: The prognosis for patients after local recurrence of osteosarcoma is poor. Complete surgical resection at the time of recurrence is essential for survival. Positive margins at the time of initial surgical resection and early recurrence appear to be poor prognostic factors.

Adolescent↗

PubMed2004

High-dose methotrexate pharmacokinetics and outcome of children and young adults with osteosarcoma.

BACKGROUND: High-dose methotrexate (HDMTX) is used frequently in combination regimens that include nephrotoxic chemotherapy. The authors evaluated the impact of factors such as age and prior nephrotoxic agents on MTX pharmacokinetics in children and young adults with osteosarcoma and examined whether MTX pharmacokinetic parameters were associated with outcome. METHODS: The authors evaluated MTX pharmacokinetics in 140 patients who were treated with 1083 courses of HDMTX on 3 consecutive studies of multiagent chemotherapy at a single institution. The influence of MTX pharmacokinetics on the outcome of 107 patients with localized disease was examined. RESULTS: Mean peak MTX concentrations > or = 1000 microM were achieved in 135 patients (96%). MTX clearance was decreased after cisplatin therapy (P = 0.01), after cisplatin in combination with ifosfamide therapy (P < 0.0001), and after MTX therapy (P = 0.003). In patients with localized osteosarcoma, a higher mean MTX area under the curve, a higher mean peak concentration of MTX, a longer mean time above a threshold concentration (500 microM), and a lower mean MTX clearance were associated with lower probability of event-free survival (EFS). Patients who had a mean peak MTX plasma concentration > 1500 microM were found to have a worse outcome (estimated 5-year EFS, 58.5% +/- 6.7%) compared with patients who had a mean peak concentration < or = 1500 microM (estimated 5-year EFS, 75.5% +/- 6.6%; P = 0.02). CONCLUSIONS: When HDMTX (12 g/m(2)) was used with multiagent therapy for patients with osteosarcoma, very high MTX exposures were associated with poorer outcome. The prospective evaluation of MTX pharmacokinetics and their relation to outcome in a large study is warranted to further substantiate the current findings and to elucidate the causative mechanism.

Adolescent↗

PubMed2004

Episcleral plaque brachytherapy for retinoblastoma.

BACKGROUND: The purpose of this study was to report our experience using episcleral plaque brachytherapy (EPBRT) to treat retinoblastoma and to demonstrate its applicability in multimodality treatment. PROCEDURE: We treated 26 tumors in 25 eyes from a group of 21 children with unilateral (n = 4) or bilateral (n = 17) retinoblastoma. The group comprised 8 girls and 13 boys; the median age was 25 months (range: 2-64 months) at the time of EPBRT. Iodine-125 ((125)I) was used for all applications. The median dose was 44 Gy (range: 35-47.6 Gy). EPBRT was administered primarily at the time of relapse after primary chemotherapy or radiation therapy. RESULTS: For eyes treated with EPBRT, the eye preservation rate was 15/25 with a median follow-up of 47 months (range: 2-198 months); the lesion control rate was 25/26 with a median follow-up of 13 months (range: 1-140 months). The median time to additional whole-eye treatment after EPBRT was 12 months (range: 2-105 months). CONCLUSIONS: Similar to previously reported series, EPBRT shows a high rate of successful tumor control as a primary treatment for retinoblastoma, as well as a secondary therapy at the time of relapse. EPBRT also allows for a clinically significant delay in the time to additional measures for the affected eye. Therefore, EPBRT should be considered as a form of local ophthalmic therapy that avoids or delays the use of external-beam radiotherapy, especially for patients primarily treated with chemotherapy who might require consolidation therapy.

Brachytherapy↗

PubMed2004

Efficacy of combined surgery and irradiation for localized Ewings sarcoma family of tumors.

BACKGROUND: Local tumor control for patients with Ewings sarcoma family of tumors (ESFT) is favorable when the primary tumor is resectable or small. Local failure rates for patients who received combined surgery and RT were reviewed to determine outcome and prognostic factors. PROCEDURES: We performed a retrospective review of all patients with localized ESFT treated with combined definitive surgery and RT between 1978 and 2001, at St. Jude Children's Research Hospital. Rates of local failure, survival, and prognostic factors for recurrence were determined in 39 patients who received combined local therapy. Systemic treatment included vincristine, actinomycin D, cyclophosphamide, and doxorubicin (6 patients), with the addition of ifosfamide and etoposide (33 patients). RESULTS: With a median follow-up of 8.7 years the 5- and 8-year survival estimates were 89.2 +/- 5.4% and 82.8 +/- 7.3%. The 8-year incidence of local failure was 10.8 +/- 5.2%. The 8-year local failure rate for patients with positive surgical margins was 17% and for negative surgical margins 5% (P = 0.25). Overall survival was improved for patients with negative surgical margins (94 vs. 71%, P = 0.052). Tumor size, site, histologic response, and radiation dose did not significantly alter the rate of local failure. CONCLUSIONS: Patients with ESFT managed with definitive surgery and irradiation have favorable local control rates. Even among patients with unfavorable prognostic factors local tumor control remained excellent.

Adolescent↗

PubMed2004

Natural history of moderate aplastic anemia in children.

BACKGROUND: Moderate aplastic anemia (MAA) in children is a rare, idiopathic condition of bone marrow insufficiency that can resolve spontaneously, persist for months or years, or progress to severe aplastic anemia (SAA). We evaluated the rate of progression to SAA. METHODS: We reviewed the records of 136 children referred for evaluation of bone marrow failure from 1978 to 2002 at St. Jude Children's Research Hospital. MAA was defined by a hypocellular bone marrow (<50%) and 2 or 3 cytopenias (absolute neutrophil count <1,500/mm(3), absolute reticulocyte count <40,000/mm(3), platelet count <100,000/mm(3)) lasting at least 6 weeks. RESULTS: Twenty-four patients met the criteria for MAA. At a median follow-up of 66 months (range, 10-293), 16 patients (67%) progressed to SAA, 5 (21%) had persistent MAA, and 3 (12%) had complete resolution of MAA. No risk factors for progression could be identified. CONCLUSIONS: When childhood MAA is treated with supportive care alone, 2/3 of patients progress to SAA.

Adolescent↗

PubMed2004

Extranodal Rosai-Dorfman disease in children.

Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease (RDD), is a histiocytic disorder that usually presents with painless massive cervical lymphadenopathy. The course is usually self-limited, but treatment may be required in cases with compression of vital organs. Patients may present with extranodal involvement only, and in these cases the clinical and histologic diagnosis may be difficult. The authors describe three patients with RDD who had exclusive extranodal disease in the head and neck area, in whom the clinical presentation mimicked other more common conditions.

Adolescent↗

PubMed2004

Thrombocytosis in an infant with high thrombopoietin concentrations.

Patients with essential thrombocythemia (ET) usually have normal thrombopoietin (TPO) concentrations because of negative feedback from thrombocytosis. TPO mutations in familial ET cases result in increased translation efficiency with excessive TPO stimulation and thrombocytosis. The authors describe an infant with a high platelet count (1300 x 103/mm3) and an elevated TPO concentration who was successfully treated with anagrelide. Sequencing of TPO revealed no genetic cause. This case may represent a case of atypical ET in which thrombocytosis results from TPO stimulation rather than clonal proliferation. Measuring TPO concentrations may be warranted for children with unexplained extreme thrombocytosis.

Blood Platelets↗

PubMed2004

Effect of fractionated ifosfamide on the pharmacokinetics of irinotecan in pediatric patients with osteosarcoma.

The combination of irinotecan (daily for 5 days for 2 consecutive weeks) and ifosfamide (daily on days 1 through 3) was investigated in children with osteosarcoma. Irinotecan pharmacokinetic investigations were performed before ifosfamide (day 1), after 3 days of ifosfamide (day 3), and 9 days after the end of ifosfamide (day 12). On day 3, the concentrations of irinotecan's active metabolite, SN-38, were below the limit of quantitation in two patients and were decreased in a third patient. The SN-38 area under the concentration-time curve remained below the day 1 value in two patients on day 12. The reduced area under the curve to the active metabolite SN-38 during ifosfamide therapy predicts a compromised efficacy of irinotecan in this combination.

Adolescent↗

PubMed2004

The incidence and prognosis of osteosarcoma skip metastases.

The poor prognosis for patients with osteosarcoma skip metastases has been established in the literature; however, most of the data in the literature concerning osteosarcoma skip metastases were collected before routine use of magnetic resonance imaging and before the use of modern multiagent chemotherapy regimens. This retrospective multiinstitutional study was done to evaluate the efficacy of magnetic resonance imaging to detect skip metastases and to evaluate the prognosis for these patients when treated with modern multiagent chemotherapy protocols. In a group of 155 patients who were younger than 26 years when diagnosed and treated for high-grade osteosarcoma of the long bones, 10 (6.5%) patients with skip metastases were identified. Eight of the 10 lesions were detected on pretreatment magnetic resonance imaging scans and two were detected only from the surgical pathology specimens. Five patients had concomitant pulmonary metastases at presentation and five patients had no other known site of diseases. All 10 patients died, with an average survival of 32.5 months (range 11-71 months). The five patients with only skip metastases at presentation survived an average of 27.2 months (range 15-44 months). Despite advances in the treatment of patients with osteosarcomas, those with skip metastases continue to have a poor prognosis, and they should be counseled regarding the limitations of current therapies.

Adolescent↗

PubMed2004

Heme oxygenase-1 messenger RNA expression is induced in peripheral blood mononuclear cells of pediatric cancer patients with systemic inflammatory response syndrome.

OBJECTIVE: To determine whether heme oxygenase-1 messenger RNA expression in peripheral blood mononuclear cells is induced in pediatric cancer patients with the systemic inflammatory response syndrome (SIRS) and whether this expression correlates with the heme oxygenase-1 products, bilirubin and carboxyhemoglobin. DESIGN: Prospective, controlled study. SETTING: A tertiary care pediatric oncology hospital. PATIENTS: Fourteen patients admitted to the intensive care unit with a diagnosis of SIRS by American College of Chest Physicians/Society for Critical Care Medicine consensus criteria and 17 control patients (off therapy, no acute illness). INTERVENTIONS: Blood for bilirubin, carboxyhemoglobin, and heme oxygenase-1 messenger RNA expression was collected at study entry. SIRS patients continued to have samples collected every 12 hrs for 1 wk or until intensive care unit discharge. Heme oxygenase-1, bilirubin, and carboxyhemoglobin levels of SIRS patients were compared with controls, and correlation between heme oxygenase-1 and products was assessed. MEASUREMENTS AND MAIN RESULTS: Within 48 hrs of study entry, maximum heme oxygenase-1 expression for all SIRS patients compared with controls was 5.5 +/- 1.0 vs. 1.1 +/- 0.1 (p < .0006). Maximum expression was > or =2.3-fold in 13 of 14 SIRS patients. Maximum heme oxygenase-1 expression also differed from minimum (5.5 +/- 1.0 vs. 1.6 +/- 0.3, p < .003). Maximum bilirubin and carboxyhemoglobin levels within 48 hrs of study entry differed between SIRS patients and controls (3.0 +/- 0.8 vs. 0.3 +/- 0.1, p = .006; and 1.2 +/- 0.2 vs. 0.6 +/- 0.1, p = .001, respectively). Bilirubin, but not carboxyhemoglobin, correlated with heme oxygenase-1 expression (p = .0013). CONCLUSIONS: Heme oxygenase-1 messenger RNA, bilirubin, and carboxyhemoglobin levels were increased within 48 hrs of admission in pediatric cancer patients with SIRS. Heme oxygenase-1 expression correlated with serum bilirubin levels. The increase in heme oxygenase-1 expression may add to the understanding of the increase in serum bilirubin observed in patients with SIRS/sepsis. These findings support a role for heme oxygenase-1 in the physiologic response to inflammatory stress.

Adolescent↗

PubMed2004

Pharmacological management of Ewing sarcoma family of tumours.

The Ewing sarcoma family of tumours comprises of a group of well-characterised neoplasms with aggressive behaviour. Despite significant progress with the use of intensive multiagent chemotherapy and local control measures, a significant proportion of patients die because of disease progression. Most treatment regimens are based on the intensification of alkylating agents and topoisomerase-II inhibitors. Using this approach, the expected survival rate is between 70 and 80% in patients with localised disease. An increasingly important complication among survivors is the development of treatment-related haematological malignancies. The outcome for patients with metastatic disease is very poor and many studies have explored the use of high-dose chemotherapy with haematopoietic stem cell transplantation (HSCT). The benefit of this approach is unclear and HSCT must therefore be considered investigational. New strategies, such as the use of immunotherapy, biological modifiers and novel classes of chemotherapeutic agents must be explored.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Treatment of intraocular retinoblastoma with vincristine and carboplatin.

PURPOSE: To evaluate the efficacy of chemoreduction using vincristine and carboplatin in preventing or delaying external-beam radiotherapy (EBRT) or enucleation in patients with intraocular retinoblastoma. PATIENTS AND METHODS: Twenty-five patients (43 eyes) with newly diagnosed intraocular retinoblastoma received primary treatment with eight courses of vincristine and carboplatin. Focal treatments were delayed until documentation of disease progression. Outcome measures for each eye were length of time to disease progression, avoidance or delay of EBRT, and globe survival. Event-free survival was defined as the length of time to EBRT or enucleation. RESULTS: Disease in all eyes responded to chemotherapy and progressed in only two patients before completion of the eight courses of therapy. Disease in all but four eyes progressed and required focal treatments. Event-free survival estimates at 2 years were 59.2% +/- 12.0% for Reese-Ellsworth group I, II, and III eyes and 26.3% +/- 9.2% for group IV and V eyes. Nineteen eyes (44.2%) required EBRT and 13 eyes (30.2%) were enucleated. The ocular salvage rate was 83.3% for Reese-Ellsworth group I to III eyes and 52.6% for group IV and V eyes. For those patients receiving EBRT, the median time from enrollment to EBRT was 9.5 months (median age at EBRT, 21 months). CONCLUSION: In combination with appropriate early intensive focal treatments, chemoreduction with vincristine and carboplatin, without etoposide, may be an alternative treatment for patients with early-stage intraocular retinoblastoma, although additional studies are needed. Patients with advanced intraocular disease require more aggressive treatments.

Antineoplastic Combined Chemotherapy Protocols↗