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Biomedical subjects

L Helson

Publications and source records attributed to L Helson.

At least 19 recordsLinked to original sources
PubMed1997

Single and double autotransplants for relapsing/refractory Hodgkin's disease: results of two consecutive trials.

To evaluate a strategy of one cycle of dose-intensive chemotherapy for patients with Hodgkin's disease in sensitive relapse and two cycles for those with refractory disease, 122 patients received dose-intensive chemotherapy followed by autotransplant in two consecutive studies. Patients with refractory disease were offered a second transplant with different conditioning in the absence of progression or excessive toxicity. CR was present after treatment in 46% while 16% died in the peritransplant period. Of 41 patients with primary refractory disease and 42 with refractory relapse, 24 and 21 respectively received a second cycle. Of these 45 refractory patients, 12 were in CR and 11 in PR after the first cycle and 10 of these 11 in PR achieved a durable CR with the second transplant. The CR rate is 37% in patients with refractory relapse and 19% in those with primary refractory disease. At a median follow-up of 4 years, median survival is 45 months. Progression-free survival of the refractory patients who could receive a second cycle was similar to that of patients with sensitive disease. A sequential transplant strategy is feasible. A subgroup of patients with refractory disease can achieve long-term survival after sequential BMT.

Adolescent↗
PubMed1996

Sporadic acute lymphocytic leukemia arising in a patient with neurofibromatosis and xanthogranulomatosis.

We present a case report of a child who developed acute lymphoblastic leukemia, neurofibromatosis, optic glioma, and xanthogranulomatosis. This complex is unusual, not previously described, and appears to be a coincidence of different diseases. The importance of this case is that it may offer a clue to the genetic base of neurofibrosis syndromes including leukemic associations.

Glioma↗
PubMed1995

Deferoxamine followed by cyclophosphamide, etoposide, carboplatin, thiotepa, induction regimen in advanced neuroblastoma: preliminary results. Italian Neuroblastoma Cooperative Group.

Based upon phase I and II studies of deferoxamine alone and in combination with cytotoxic agents cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT), we initiated a single arm multicentre trial in 1992 for advanced neuroblastoma. 57 of 65 patients who entered the trial were evaluable. Following 4 courses of the D-CECaT, almost all the patients underwent surgery. Toxicity was moderate and mainly reversible myelosuppression. The post-surgically defined responses in stage 3 high risk, stage 4 moderate risk and stage 4 high risk patients included 24 complete responses, 26 partial responses, and 3 minor responses, and 4 patients had progressive disease. These patients are being followed to determine the impact of this programme on their overall survival.

Adolescent↗
PubMed1995

Camptothecin cytotoxic effects in vitro: dependency on exposure duration and dose.

A survey of in vitro cytotoxic effects of camptothecin in human epitheliod sarcoma, colon, breast and ovarian carcinomas, glioblastoma, and neuroblastoma (PNET) cell lines, was done. We chose the MTT assay to measure survival and observed that 24 h exposures to camptothecin caused consistently greater toxicity than 1 h exposures. The LD50 for camptothecin was in the 12.5-25 ng/ml range. There was a 10-fold range of growth rates measured by OD after 5 days exposure and varied expression of MDR1 in these cell lines--none of which could be correlated with tumor sensitivity to drug. The most sensitive cell lines were colon and glioblastoma, and the most resistance were ovarian, breast and epithelioid sarcoma.

Antineoplastic Agents, Phytogenic↗
PubMed1994

Incidence and treatment of tumor lysis syndrome in patients with acute leukemia.

Tumor lysis syndrome (TLS) is a complication associated with electrolyte abnormalities that is observed in patients with acute leukemia who are receiving intense doses of chemotherapy. Forty-one patients with acute leukemia were treated with high-dose combination chemotherapy and were evaluated for TLS. A grading system developed for the evaluation of these patients was applied. Grade I tumor lysis was observed in 22 patients, grade II TLS in 2 patients and grade III in 1 patient. All patients were treated with intravenous fluids, mannitol, allopurinol and in some patients, aluminum-based antacids. Treatment for TLS prior to intensive chemotherapy reduced morbidity and mortality associated with high-dose chemotherapy for acute leukemias.

Adolescent↗
PubMed1994

Phase I-II trial of high dose Ara-C, carboplatinum, etoposide and steroids in patients with refractory or relapsed lymphomas.

Thirty-three patients, including 20 with non-Hodgkin's lymphomas (NHL) and 13 patients with Hodgkin's disease, were treated with a combination of high dose Ara-C 3 gm/m2 over 3 h, carboplatinum 300 mg/m2 over 15 min, etoposide 300-750 mg/m2 continuous infusion over 24 h and solumedrol 1250 mg. Probantheline was given prophylactically. The etoposide dose was escalated from 300 mg/m2 to 600 mg/m2 to 750 mg/m2. The median age was 44 years (range 28-63). Median Karnofsky performance status was 80 (range 60-100). Patients treated included: primary refractory six, first relapse 14, > first relapse seven, and resistant relapse six. Responses were seen in 11 patients (33%; 95% CI 17-49). Of note, no responses were seen in ten patients receiving < 750 mg/m2 etoposide vs. 11/23 patients receiving 750 mg/m2 etoposide (p = 0.013). Responses were seen in patients who were refractory to previous chemotherapy and occurred in all sites. Toxicity was tolerable with most patients not requiring hospitalization following chemotherapy. Two patients died on study: one of Guillain-Barre syndrome and the other of a sudden death. Severe mucositis was not observed. High dose etoposide based salvage chemotherapy offers a greater probability of response than lower dose etoposide. This regimen is well tolerated and can be administered with relatively brief hospitalization.

Adult↗
PubMed1993

delta-Aminolevulinic acid effects on neuronal and glial tumor cell lines.

Acute intermittent porphyria (AIP) or precursor syndrome is a well described neuropathic clinical entity with incompletely known etiology. The most prominent biological abnormalities associated with this syndrome are elevations in serum and hepatic delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). We determined the impact of ALA and PBG on human neuroblastoma and glioblastoma tumor cell survival as measured by the MTT assay. ALA proved to be cytotoxic in neuroblastoma cells, while PBG lacked cytotoxic effects. This cytotoxic effect of ALA could be enhanced by deferoxamine and diminished by heme, presumably through modulation of ALA synthesis. In conclusion, ALA excess may prove to be associated with the development of neuropathy in AIP.

Aminolevulinic Acid↗
PubMed1993

A saturation threshold for taxol cytotoxicity in human glial and neuroblastoma cells.

The cytotoxic effects of taxol at concentrations of 0.001-1.0 microgram/ml were determined in two human glioblastoma multiforme, two neuroblastoma and two primitive neuroectodermal tumor cell lines. The neuroectodermal cell lines were established from previously treated patients, while the glioblastomas were from untreated patients. At exposure durations of 1, 4 and 24 h there was an inverse taxol concentration-survival relationship for all six cell lines as measured by the MTT method. Significant differences in sensitivity to taxol among these cell lines were observed; the most resistant cell line SK-N-FI is characterized by very high levels of MDR1 expression and the most sensitive SK-N-AS by very low levels. An additional level of complexity concerns a saturation threshold for taxol-induced cytotoxic effects which when reached precludes additional effects of prolonged or additional exposure. Tumors of the brain and peripheral nervous system appear to be sensitive to taxol. However, dosage necessary to maximize cytocidal effects in tumors requires knowledge of at least the range of each tumors constitutive sensitivity to taxol and a way to optimize drug delivery.

Brain Neoplasms↗
PubMed1993

D-CECaT: a breakthrough for patients with neuroblastoma.

In view of the high relapse rate following chemotherapy for patients with advanced neuroblastoma (NB) and primitive neuroectodermal tumors (PNET), we designed a novel chemotherapy program which incorporated the iron chelator deferoxamine. The purpose of the deferoxamine was to sensitize the cells to standard chemotherapy. The D-CECaT regimen contained (in mg/m2): deferoxamine 4500 during days 1-5; cyclophosphamide 600 mg over days 6 and 7; etoposide 300 mg over days 7 and 8; carboplatin 100 mg over days 7 and 8; and thiotepa 30 mg over days 6-8. Between October 1989 and May 1992 we entered 23 advanced NB and two PNET patients. Sepsis occurred in four courses, nausea and vomiting in 30 courses, and 50 courses required blood and platelets. Responses observed in previously untreated patients with stage III NB: six out of six CR (17+ to 41+ months), with stage IV NB, nine out of 11 CR (14+ to 28+ months), two out of 11 VGPR (22+ months), with stage IV PNET two out of two CR (1+ to 35+ months). With previously treated and failed stage IV NG, two out of six VGPR for 19+ and 20 months, and four out of six PR 1, 8, 9 and 11 months. Median survival for 19 new patients was 22+ months (6 to 41+ months; two patients in CR died at 7 months during adjuvant autologous marrow transplant). In conclusion, D-CECaT is an effective initial cytoreductive regimen for advanced stage NB/PNET patients. Additional patients and studies are required to determine its use as an alternative to autologous bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Propantheline prevention of mucositis from etoposide.

Mucosal toxicity is dose limiting for etoposide. This may be related to the direct effects of etoposide on the mucosa. Twelve patients receiving etoposide 1800 mg/m2 as part of a myeloablative pre-transplant regimen were randomized to receive propantheline 30 mg or placebo orally every 6 h for six doses. Mucositis was less frequent (2 of 6 vs 5 of 6) and less severe (p = 0.05) in the propantheline arm. There were no differences in tumor response or survival between the two groups. Propantheline is an anticholinergic that causes xerostomia by decreasing salivation. Propantheline may reduce the salivary excretion of etoposide and could reduce its toxic effects on the mucosa. Propantheline is effective in reducing the incidence and severity of mucositis in patients receiving high-dose etoposide.

Adult↗
PubMed1992

Choroid plexus carcinoma--responses to chemotherapy alone in newly diagnosed young children.

Choroid plexus carcinoma (CPC) arising in the infant poses several treatment dilemmas. The tumor is often not totally resectable at presentation given its large size and tendency to invade adjacent brain. Because of its predisposition to regrow and metastasize, some form of postoperative cytotoxic therapy is required. Chemotherapy (CHT), as opposed to radiotherapy (RT), has a more desirable risk/benefit role in infants, since it is relatively sparing of late neurologic sequelae. Three young male children presented with large intraventricular CPC at 9, 18, and 27 months of age. One child had subarachnoid metastases at diagnosis and the other two had localized disease. Subtotal resections were accomplished and all three required VP shunts. Initial CHT consisted of four monthly courses of cisplatin (20 mg/m2) and etoposide (100 mg/m2), both administered intravenously, daily, for five days. After four courses, two children had complete responses and one had stable disease. Additional CHT was given but one child developed a local recurrence and another diffuse CNS metastases. Both died with intratumoral hemorrhages at 5 and 57 months following diagnosis. The third child remains in continuous remission 46 months after diagnosis. None of the children received RT. Chemotherapy may permit long term deferral of RT. More aggressive CHT regimens should be explored in infants with CPC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Higher cure rates in acute leukemia: now more probable with increasingly effective induction therapy.

Traditional therapy of acute myelogenous leukemia has not cured more than 10% of patients and, of acute lymphoblastic leukemia not more than 30% of adults. In part, this is due to the lack of agents effective enough to induce remissions of such quality that cure is possible. The introduction of mitoxantrone and its use in high dose with high-dose cytarabine for induction therapy, raises the possibility of an increased cure rate of acute myelogenous leukemia and acute lymphoblastic leukemia.

Acute Disease↗
PubMed1992

Deferoxamine, cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT): a new cytoreductive chelation-chemotherapy regimen in patients with advanced neuroblastoma.

Thirteen patients with Stage III (3 patients) or Stage IV (10 patients) neuroblastoma were treated with a new iron chelation-cytotoxic therapy regimen. Deferoxamine given for five consecutive days followed by 3 days of cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT) caused moderate to severe myelotoxicity. In 39 courses there were four episodes of sepsis; platelet and packed red blood cell transfusions were required in 72% and 82% of courses, respectively. Mild nausea and vomiting occurred in 52% of courses. Objective responses after two courses were observed in 12 of 13 patients. Three of four partial responses were achieved in previously treated relapsed patients, and seven of eight complete responses (four of which were surgically documented) were achieved in previously untreated patients. This cytoreduction regimen appears to be an improvement over other initial induction regimens and may be worth testing in larger populations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Hemopoietic stem cell processing: comparison of progenitor cell recovery using the Cobe 2991 cell washer and the Haemonetics V50 apheresis system.

Using 24 bone marrow (BM) harvests intended for cryopreservation and transplantation, we compared the use of the Cobe 2991 cell washer (2991) and the Haemonetics V50 apheresis system (HV50) for automated BM processing. Our in vitro data indicate that while the mononuclear cell (MNC) concentration of the HV50 product was significantly greater than that of the 2991, the overall MNC recovery of the two products was equivalent. In addition, although the concentration of CFU-GM and BFU-E in the products was equivalent, recovery of these progenitors in the 2991 product was significantly greater than those of the HV50 product. There was no significant difference in either the final product concentration or the overall recovery of cells bearing the primitive myeloid antigens, CD33 or CD34, between the two methods. The HV50 product volume, the red cell and the granulocyte mass were significantly lower than those of the 2991. We conclude that the advantages gained through the use of each machine should be evaluated within the context of the specific intention for the graft. Future advances in the identification and understanding of the primitive stem cell will aid in attempts to evaluate the methods used to isolate these cells.

Adolescent↗