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V Papadakis,
I J Dunkel,
L D Cramer,
E Kramer,
E Papadopoulos,
S Goldman,
R J Packer,
M Willoughby,
D Baker,
J Garvin, S Strandjord,
P Coccia,
A M Kaplan,
M Klemperer,
J L Finlay
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ABSTRACT: Forty-two patients (29 newly diagnosed) with high grade gliomas (n = 37), medulloblastoma (n = 2) or non-biopsied tumors (n = 3) with supratentorial (n = 24), brain stem (n = 11), posterior fossa (n = 5) or spinal (n = 2) location were eligible for this study with adequate organ function and no bone marrow tumor infiltration. Median patient age was 12.2 years (range, 0.7-46.8). A total of 600 mg/m2 BCNU, 900 mg/m2 thiotepa and 1500 or 750 mg/m2 etoposide (VP-16) was administered followed by autologous bone marrow reinfusion (ABMR). Twenty-one newly diagnosed patients received local irradiation (RT) post ABMR. Nine early deaths were observed (21%), as well as one secondary graft failure. Half of the patients aged 18 years or older experienced toxic deaths, whereas only 15% of patients younger than 18 years experienced toxic death (P = 0.05). Of 25 evaluable newly diagnosed patients, 20% achieved complete remission (CR) and 4% partial remission (PR), while 28% remained in continuing complete remission (CCR) and 44% remained with stable disease prior to RT. Of eight evaluable patients with recurrent disease, one achieved CR and two PR, while one remained in CCR and four with stable disease for 1 to 110.2 months. Overall survival was 36%, 24% and 17% at 1, 2 and 3 years following ABMR, with three newly diagnosed patients and one patient treated for recurrent disease being alive, without disease progression 64.4, 67.0, 86.3 and 110.2 months after ABMR, respectively. The combination of high-dose BCNU/ thiotepa/VP-16 has substantial toxicity but definite activity for high risk CNS tumors. Similar protocols with lower toxicity merit further evaluation in both newly diagnosed and recurrent CNS tumors.
Bone Marrow Transplantation 08/2000; 26(2):153-60. · 3.75 Impact Factor
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ABSTRACT: Multimodal cancer therapy for pediatric head and neck tumors may be associated with significant developmental orofacial morbidity. This report details these effects in a child (C.I.) diagnosed at 2.5 years of age with a rhabdomyosarcoma, primary to the left buccinator. This case is of interest as C.I. has an unaffected identical twin (D.I.) for comparative study. Both were assessed by comparing panoramic radiographs and lateral and frontal tracings of cephalometric radiographs obtained at 8.25 years of age. C.I. had multiple dental anomalies which included agenesis, ectopia, crown malformation, and root malformation. Root malformation, ectopia, and agenesis were restricted to the left dentition, whereas crown malformation was noted bilaterally. C.I. had a generalized craniofacial skeletal hypoplasia relative to D.I. in all three planes, growth defects were greater on the side of the tumor, and the mandible was affected more than the nasomaxillary complex.
Pediatric dentistry 10/1989; 11(3):227-31. · 1.02 Impact Factor
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ABSTRACT: Leukemic relapse following bone marrow transplant (BMT) is generally due to the recurrence in recipient cells, but may rarely occur as a result of donor cell transformation. Donor cell relapse is generally identified using cytogenetic markers such as the sex chromosomes. Recently, molecular techniques have been used to identify the origin of bone marrow cells by their DNA restriction fragment length polymorphisms. We describe the case of a male pediatric patient who had a leukemic relapse 30 months following BMT from his sister. Both cytogenetic and molecular techniques were used to identify the origin of the leukemic relapse. Cytogenetic analyses indicated the absence of the Y chromosome and the presence of a donor cell type 9qh polymorphism, suggesting a donor cell relapse. Molecular analyses also indicated the absence of the Y chromosome but demonstrated the recurrence of recipient DNA markers from three other chromosomes, suggesting a recipient cell relapse. While the leukemic cell lineage cannot be definitively assigned in this case, our results suggest that caution must be exercised when assigning leukemic cell lineage following post-BMT relapse.
Blood 06/1989; 73(7):2033-40. · 9.90 Impact Factor
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Progress in clinical and biological research 02/1988; 271:237-48.
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ABSTRACT: CNS dysfunction, especially impaired cerebellar function, is the dose-limiting toxicity associated with high-dose cytosine arabinoside, which precludes doses of greater than 48 g/m2. Four hundred eighteen patients between the ages of 2 and 74 years with leukemia or lymphoma received 36 to 48 g/m2 cytosine arabinoside either alone or with anthracycline antibiotics, 4'-(9-acridinylamino) methane sulfon-m-anisidine (m-AMSA), or total body irradiation. In only 35 of 418 patients (8%) did severe cerebellar toxicity develop; it was irreversible or fatal in four (1%) patients. The age of the patient was a critical factor in the incidence of severe cerebellar toxicity. Patients greater than 50 years old had a statistically significant greater incidence of cerebellar toxicity compared with younger patients (26/137, 19%, v 9/281, 3%; P less than .0005, chi 2). Neither the diagnosis, disease status, sex, nor the regimen altered the incidence of severe cerebellar toxicity (when corrected for age). A second course of high-dose cytosine arabinoside, administered to 62 patients, did not increase the incidence of severe cerebellar toxicity, which occurred in five (8%) of these patients. Two of the five patients had severe toxicity with the initial course. Of the 60 patients with no antecedent cerebellar dysfunction, three (5%) had severe toxicity with the second course: one of 41 patients were less than 50 years old; two of 19 patients were greater than or equal to 50 years. Since the occurrence of severe cerebellar dysfunction is greatly affected by age, reduced doses of high-dose cytosine arabinoside should be given to patients greater than 50 years old, and methods for reducing the cerebellar toxicity should be investigated in these patients.
Journal of Clinical Oncology 07/1987; 5(6):927-32. · 18.37 Impact Factor
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Pediatric dentistry 07/1987; 9(2):105-10. · 1.02 Impact Factor
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Progress in clinical and biological research 02/1985; 175:501-5.
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ABSTRACT: The effect of a multi-agent regimen on oropharyngeal candidiasis (OPC) prophylaxis in 16 consecutive pediatric bone marrow transplant patients was assessed. The multi-agent regimen consisted of: 1) debriding all mucous membrane surfaces within the oropharyngeal cavity with povidone-iodine 4 times a day, 2) swabbing all mucous membrane surfaces within the oropharyngeal cavity with nystatin 4 times a day, and 3) Ketoconazole given daily by mouth. Multi-agent regimen therapy was initiated on the day marrow ablative therapy began, and was terminated when the patient's absolute neutrophil count recovered to above 500/mm3. Baseline oropharyngeal fungal cultures indicated that 8 out of 16 (50%) of the patients were Candida carriers. Subsequent surveillance cultures indicated that 13 out of 16 (81.3%) of the patients had negative oropharyngeal fungal cultures during the entire period they were on the multi-agent regimen. The remaining three patients had negative oropharyngeal fungal cultures by the end of the experimental period. None of the patients developed Candida esophagitis or sepsis. The above regimen is an effective and non-toxic method to prevent oropharyngeal candidiasis in pediatric BMT patients.
The American journal of pediatric hematology/oncology 02/1985; 7(1):82-6.
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ABSTRACT: Methotrexate has been used as the mainstay therapy to prevent or ameliorate graft-versus-host disease (GVHD) in allogeneic bone marrow transplantation. We began a nonrandomized study in which methotrexate was not given routinely. Fifty-five patients underwent transplant for acute leukemia (44 patients), aplastic anemia (6 patients), and other malignancies (5 patients). Methotrexate was given to 34 patients (MTX +) and was withheld in 21 patients (MTX -). Median (range) age of patients was 12 (0.8-43) years in the MTX + group, and 16 (3-45) years in the MTX- group. Mean days (+/- SEM) to engraftment (neutrophils greater than 500/microL, and platelets greater than 20,000/microL untransfused) occurred earlier in the MTX- patients (19.6 +/- 1.4 v 24.9 +/- 1.8 days for granulocytes, and 19.3 +/- 1.5 v 27.4 +/- 2.8 days for platelets, P less than .05). There were no statistically significant differences between the patient groups for the incidence or severity of GVHD (10/34 in the MTX + group had grade O-l GVHD compared to 9/21 in the MTX- group). The interstitial pneumonitis occurred at a significantly increased rate in patients who received methotrexate (15/34) compared to those patients who did not (3/21) (P = .02). However, there was also a significant relationship between the interstitial pneumonitis and the preparative regimen: if the preparative regimen contained 1,000 rad single fraction total body irradiation, 8/14 patients were affected compared to 5/22 patients affected when 1,200 rad fractionated total body irradiation was used (P = .03). Because methotrexate significantly retards hematopoietic reconstitution, randomized trials for GVHD prevention are recommended.
Blood 08/1984; 64(1):215-20. · 9.90 Impact Factor
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ABSTRACT: Neuroblastoma and Ewing's sarcoma are examples of pediatric cancers in which disseminated disease is often present at diagnosis or develops later in spite of combination therapy. The demonstration that marrow-ablative doses of chemotherapy can increase tumor cell kill, and that autologous bone marrow can be cryopreserved and reinfused into the patient to reverse such marrow ablation, has stimulated interest in this approach to refractory childhood cancers. We present results of treating eighteen patients with recurrent neuroblastoma and Ewing's sarcoma resistant to conventional therapy. We used supralethal doses of melphalan, supported by reinfusion of previously cryopreserved autologous bone marrow. Seven of 10 neuroblastoma and six of eight Ewing's sarcoma patients had complete or partial responses, lasting for a median of 6 months (neuroblastoma) and 3 months (Ewing's sarcoma). Prolonged hospitalization, pancytopenia complicated by sepsis, and reversible gastrointestinal toxicity were the major side effects. These results suggest this approach should be tested in therapeutic trials at an earlier disease stage in children who have cancers with a predictably bad prognosis.
The American journal of pediatric hematology/oncology 02/1984; 6(1):17-26.
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ABSTRACT: Thirty-three adult and pediatric patients with refractory malignancies were treated with escalating doses of melphalan (120-225 mg/m2 IV over 3 days) followed by reinfusion of previously harvested and cryopreserved autologous marrow. The hematological and nonhematological toxicities and the therapeutic effects of this regimen were evaluated. Increasing doses of melphalan did not alter the rate of decline nor the recovery of peripheral blood counts. Granulocyte (greater than 500/microL) and platelet count (greater than 20,000/microL) recovery occurred in a median of 19 (range 12-54) and 24 (range: 12-54) days after bone marrow transplantation, respectively. Five patients experienced severe infection, three of which were fatal, and one patient died due to thrombocytopenic hemorrhage. Toxicity to the gastrointestinal system was dose limiting. The maximum tolerated dose of melphalan was 180 mg/m2; only three of 24 patients experienced severe stomatitis, esophagitis, and diarrhea at this level or less, while eight of nine patients at 225 mg/m2 were affected (p less than 0.005). Administration of cyclophosphamide (300 mg/m2 IV) 1 week before melphalan therapy did not reduce the incidence of severe gastrointestinal toxicity. Plasma melphalan concentration peaked 30-60 min after infusion (4.8-11.5 micrograms/mL) but declined rapidly. Cerebrospinal fluid concentration was 10% of the corresponding plasma concentration and was undetectable at 3 hours. Antitumor responses occurred in nine of 13 patients with malignant melanoma (five complete and four partial remissions), and ranged 2-12+ months with a median of 5 months. Four of six neuroblastomas demonstrated responses (three complete and one partial remission( lasting a median of 7.5 (range: 5-10) months. Other tumors in which this regimen had activity included breast cancer and Ewing's sarcoma. The overall response rate for the 33 patients was 30% complete remissions (10 patients) and 21% partial remissions (seven patients). High dose melphalan and autologous bone marrow transplantation is a promising therapy for patients with malignancies for which no effective treatment is known or for patients whose cancer is refractory to conventional therapeutic agents.
Journal of Clinical Oncology 07/1983; 1(6):359-67. · 18.37 Impact Factor
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ABSTRACT: The effect of dental evaluation and treatment prior to bone marrow transplantation in 11 pediatric patients was assessed. Oral complications associated with marrow ablative therapy and the immediate posttransplant period (Days 0-35) were also studied. Oral complications during marrow ablative therapy included: xerostomia (2/11 patients) and parotitis (1/11 patients). Oral complications in the immediate post-transplant period (Days 0-35) included: mucositis (11/11 patients); moniliasis (9/11 patients); and stomatitis associated with acute G.V.H.D. (3/9 patients receiving allogenic marrow transplants). The onset of the mucositis in the posttransplant period usually occurred at the nadir of the white blood cell count and resolved when the absolute neutrophil count was approximately 500/m3. The onset of moniliasis in the posttransplant period was usually 1-2 days after the onset of the mucositis. Resolution of the moniliasis usually paralleled resolution of the mucositis. No patient developed an infectious and/or hemorrhagic complication of odontogenic origin.
The American journal of pediatric hematology/oncology 02/1983; 5(1):53-7.
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ABSTRACT: Eleven patients received allogeneic bone marrow from all HCA-identical sibling for the treatment of acute leukemia. The preparative regiment included high-dose cytosine arabinoside (Ara-C), 3 g/m2q 12 h for 12 doses, and 1000 rad single-fraction total body irradiation (5 patients) or 1200 rad fractionated total body irradiation (6 patients). The 5 patients receiving the 1000 rad single-fraction regimen were transplanted in relapse, while the 6 patients receiving the 1200 rad fractionated program were transplanted during remission. Both regimens were well-tolerated, but the single-dose radiation regimen was associated with more severe skin problems. Bone marrow engraftment was documented in 10 of 10 evaluable patients, occurring 2-3 weeks after marrow infusion. No recurrences have been observed during the brief follow-up time.
Medical and Pediatric Oncology 02/1982; 10 Suppl 1:235-8.
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ABSTRACT: Symptomatic spinal cord compression requires emergency treatment to alleviate symptoms and to avoid irreversible damage. We describe a successful decompression by low dose radiation to a progressing neuroblastoma in a child. Magnetic resonance imaging post radiation should be performed to assess the response of the tumor to radiation.
Anticancer research 20(6C):4687-90. · 1.73 Impact Factor
