High-dose carboplatin,cyclophosphamide, and BCNU with autologous bone marrow support: excessive hepatic toxicity

Summary Intensive doses of carboplatin, cyclophosphamide, and BCNU with autologous bone marrow support were given to four patients with advanced melanoma. Three developed clinically diagnosed, severe venoocclusive liver disease, which was fatal in two cases. The dose of carboplatin (450 mg/m²) was comparable with that used in ambulatory regimens. At the doses and schedule employed, this three-drug combination produced excessive hepatic toxicity. Caution is suggested when giving carboplatin in combination with intensive doses of other chemotherapeutic agents with known hepatotoxic potential. Supported in part by National Institutes of Health grant CA-14236-16     

High-dose cyclophosphamide or melphalan with escalating doses of mitoxantrone and autologous bone marrow transplantation for refractory solid tumors

As the dose-limiting toxicity of mitoxantrone is hematological, the drug is suitable for dose escalation and use in intensive chemotherapy followed by autologous bone marrow rescue. Adult patients with therapy-resistant solid tumors received a regimen of high-dose cyclophosphamide (7 g/m2) and escalating doses of mitoxantrone in dose steps of 30, 45, 60, and 75 mg/m2. Both drugs were given i.v. on 3 consecutive days. Despite the addition of mesnum (3.5 to 7 g/m2), hemorrhagic cystitis occurred on the second day in four of eight patients, irrespective of the mesnum or mitoxantrone dose. Therefore, the cyclophosphamide in the combination regimen was replaced by high-dose melphalan (180 mg/m2). Mucositis was dose limiting at 75 mg/m2 of mitoxantrone. Responses were seen in eight of ten evaluable patients with four complete responses. Three responders received, after the autologous bone marrow transplantation program, radiotherapy or surgery on pretreatment bulky tumor localizations. Five patients still have disease-free survival after 9 to 36 mo. Pharmacokinetic studies of mitoxantrone were performed by high-performance liquid chromatography with UV detection. The plasma disappearance of mitoxantrone fitted into a three-compartment model with a mean t1/2 alpha of 10 min, a mean t1/2 beta of 96 min, and a slow elimination phase of 172 h. The mean distribution volume was 4294 +/- 3836 liters. We conclude that the high-dose cyclophosphamide-mitoxantrone regimen led to unexpected bladder toxicity, but the combination of melphalan (180 mg/m2) and mitoxantrone (60 mg/m2) can probably be given without major extramedullary toxicity. However, more patients should be evaluated at this dose before definite conclusions can be drawn about toxicity.     

High-dose melphalan with 6-hydroxydopamine-purged autologous bone marrow transplantation for poor-risk neuroblastoma

Long-term results are presented of 28 patients who were diagnosed with neuroblastoma at more than 12 months of age and who received melphalan 180 mg/m2 (n = 6) or 240 mg/m2 (n = 22) to consolidate remissions of Stage IV disease or to control refractory disease. Twenty-four patients also received dianhydrogalactitol 180 to 240 mg/m2, and 11 received total body irradiation 450 to 600 cGy. Autologous bone marrow transplantation (ABMT) was performed with marrow that was unpurged (n = 2) or purged ex vivo (n = 26) with 6-hydroxydopamine (6-OHDA) 20 micrograms/ml plus ascorbate 200 micrograms/ml. The median time to an absolute neutrophil count of 500/microliters was 21 days and to self-sustaining platelet counts more than 20,000/microliters, 28 days. One patient required infusion of unpurged reserve marrow. Two groups of patients underwent ABMT: (1) 17 patients (Group I) who were in first remission a median of 7 months after diagnosis; and (2) 11 patients (Group II) who had refractory disease or were in second remission. For Group I, event-free survival was 29% at 12 months and 6% at 24 months post-ABMT. All Group II patients died of disease or ABMT-related toxicity. Overall, of the 28 patients, one is a long-term relapse-free survivor; five died of ABMT-related toxicity; ten patients with tumors present at ABMT had progressive disease within 6 months of ABMT; and 12 patients with no measurable disease at ABMT relapsed 4 to 32 months (median, 12) post-ABMT. Among the latter, six relapses involved the primary site, and six were restricted to distant sites. These results--in accord with the long-term outcome in other series--suggest that for neuroblastoma high-dose melphalan cannot be relied on to ablate residual disease or to salvage patients with refractory tumors. In addition, the pattern of relapse in several patients could be explained by infusion of incompletely purged autografts; this would support recent laboratory evidence that 6-OHDA/ascorbate is a suboptimal purging method.     

High-dose melphalan and autologous bone marrow transplant for relapsed acute leukaemia

Summary Seven patients with relapsed acute leukaemia were treated with high-dose melphalan (HDM) followed by the infusion of autologous cryopreserved remission marrow. Toxicy was minimal and all seven patients had a complete response. Four patients are still in unmaintained remission at 14, 13, 10, and 3 months, the first two having received a second course of HDM to consolidate the result. The role of HDM as a form of intensification therapy for patients with acute myeloid leukaemia in first remission should be investigated.     

High-dose combination alkylating agent chemotherapy with autologous bone marrow support for metastatic breast cancer

Seventeen patients with metastatic breast cancer were treated with a high-dose combination chemotherapy regimen and autologous bone marrow support. Thirteen patients had prior combination chemotherapy. Fifteen patients were treated with a phase II regimen of cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (600 mg/m2). Bone marrow harvest and reconstitution were uncomplicated. All patients became profoundly myelosuppressed. Fourteen of 16 evaluable patients (88%) responded, including six complete responses (CRs) (38%). The median time to tumor progression was 5 months. The median survival was 8 months. CRs occurred more frequently in patients with no prior chemotherapy for metastatic disease, inflammatory breast cancer; and patients treated within 3 months of first recurrence. The rate of tumor regression was rapid, with a median of 11 days to partial response (PR) and 12 days to CR. Those patients achieving a PR by day 7 had a greater likelihood (P = .03) of attaining a CR than those patients whose PR occurred later. Three deaths (18%) occurred, all in women with inflammatory breast cancer treated with prior chemotherapy. High-dose combined alkylating agent therapy produced high PR and CR rates in metastatic breast cancer patients, most of whom had failed prior chemotherapy. The rate of tumor regression was rapid. Current efforts are directed at developing a regimen using drugs specifically active in breast cancer, with an intent of combining an effective high-dose regimen with additional modalities of therapy in the treatment of breast cancer.     

High-dose combination alkylating agents with autologous bone marrow support: a Phase 1 trial

Twenty-nine patients were treated with 31 courses of high-dose combination cyclophosphamide, cisplatin, and carmustine (BCNU) with and without melphalan with autologous bone marrow support. Toxicity was dose related. The maximum tolerated dose for cyclophosphamide, cisplatin, and BCNU in this combination in mg/m2 was 5,625, 165, and 600, respectively. Further dose escalation was precluded by the development of multiple organ toxicity, including venoocclusive disease, refractory thrombocytopenia, and hypertension. Melphalan added to the three-drug combination produced excessive renal and gastrointestinal toxicity. Objective tumor regression occurred in 21 of 25 evaluable cases. The results suggest that selected alkylating agents can be combined in full or nearly full doses before nonmyelosuppressive dose-limiting toxicity precludes further escalation.     

High-dose cyclophosphamide, thio-TEPA, etoposide with autologous bone marrow transplantation for refractory cancers

We studied high-dose chemotherapy with autologous bone marrow transplantation (ABMT) for 10 patients with malignant lymphoma or breast cancer refractory to conventional chemotherapy. Conditioning regimen was consisted of cyclophosphamide 60 mg/kg/day, thio-TEPA 6 mg/kg/day, Etoposide 500 or 600 mg/m2/day for 3 consecutive days. Of 9 patients with measurable lesions, there were 5 with complete responses (CR) and 4 with partial responses (PR). Severe bone marrow suppression, mucositis, and diarrhea were observed in all patients. Furthermore, biliary stasis, which was unpredictable side effect, was observed in most patients. So, mucositis and/or hepatotoxicity were thought to be the dose-limiting factors. But these were not life-threatening and clinically manageable. All patients were received recombinant human granulocyte colony stimulating factor (rhG-CSF) at a dose of 300 micrograms/m2/day and which was effective for shortening the duration of leukopenia. In vitro Colony Forming Unit-granulocyte macrophage assay (CFU-GM assay) showed a significant correlation between the ability of colony formation and the days to recovery of granulocytes.     

High-dose melphalan with autologous bone marrow transplant. Treatment of poor prognosis tumors

Seventeen patients were treated with high-dose melphalan with autologous bone marrow transplant (ABMT) and cyclophosphamide pretreatment. All of the patients had marrow reconstitution. Although there was one death caused by infection, high-dose melphalan with ABMT causes toxicity that is generally acceptable, and can achieve a high-response rate, but with responses of short duration in tumors resistant to standard-dose combination chemotherapy. In other poor-prognosis tumors that are sensitive to chemotherapy, or can be debulked surgically, or locally irradiated, high-dose melphalan with ABMT given as late intensification therapy may significantly prolong time to relapse, and ultimately prolong survival.     

High-dose combination chemotherapy with autologous bone marrow transplantation in breast carcinoma

Twelve patients with breast carcinoma were treated with high-dose combination chemotherapy supported by autologous bone marrow transplantation (ABMT). Seven of them had advanced metastatic disease and received 12 cours of A treatment, response rate (CR +PR) was 71.5% (CR: 1, PR: 4, NC: 2 and PD: 0) and it should be noted that all 4 patients who had received adriamycin 150 mg+5-fluorouracil 1,500 mg divided in two consecutive days or equivalent high-dose of other chemotherapeutic regimen responded (CR: 1 and PR: 3). To the therapy Five other patients received ABMT-supported adjuvant chemotherapy because of high risk of recurrence. One of them died of unrelated cause and other 4 are free of disease at 11, 14, 17 and 17 months following this treatment. A major toxicity was of myelosuppression and nadirs of neutrophils were 100-1,800 on days 9-19 (median: 400 on day 12), neutrophils recovered rather rapidly to levels of greater than or equal to 1,000, greater than or equal to 1,500 and greater than or equal to 2,000 by day 15, 16 and 17, respectively. High-dose combination chemotherapy with ABMT seemed quite effective in advanced breast carcinoma and a similar approach in adjuvant setting has also been suggested.     

High-dose chemotherapy with autologous bone marrow support in advanced malignant melanoma

Eight patients with advanced malignant melanoma were treated with high-dose melphalan (80-90 mg/m2) and BCNU (600-800 mg/m2). In all patients autologous bone marrow preservation was performed prior to therapy. Bone marrow was stored for 48 h in a refrigerator at 10 degrees C and reinfused 48 h post-therapy. Three patients had a complete response (CR), 1 a partial response and 4 patients no response. Two patients with CR died 4 and 5 months after therapy. One had an interstitial pneumonitis and 1 patient died from unknown cause. The third patient had a relapse 12 months after therapy. Major side effects were severe nausea/vomiting and a mild mucositis. Two patients suffered from BCNU-related encephalopathy. All patients had a full hematologic reconstitution after 6 weeks. High-dose chemotherapy with autologous bone marrow support achieves a high response rate. Long-term disease-free survival, however, was not seen with this approach.     

Busulfan, cyclophosphamide, and melphalan conditioning for autologous bone marrow transplantation in hematologic malignancy

Sixteen patients with poor-prognosis acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL) underwent conditioning with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BUCY-2) plus melphalan (90 or 135 mg/m2) and autologous bone marrow transplantation (AuBMT) in a phase I study. At the melphalan dose of 90 mg/m2, grade greater than or equal to 3 regimen-related toxicity (RRT) was observed in five patients (31%; 95% confidence interval [CI], 11% to 59%), with hepatic (venoocclusive disease [VOD]) and urinary (hemorrhagic cystitis) RRT being the most frequent complications. Further escalation of the melphalan dose to 135 mg/m2 was deemed excessively toxic, as three of five patients had grade greater than or equal to 3 RRT. Following this experience, 21 patients with multiple myeloma (MM) and chronic myelogenous leukemia (CML) were treated with BUCY-2 plus melphalan 90 mg/m2 and AuBMT in separate studies. Three of these patients--all with extensively pretreated MM--had grade greater than or equal to 3 RRT (14%; 95% CI, 3% to 36%); no others had grade greater than or equal to 3 RRT. Therefore, a total of eight of the 37 patients (22%; 95% CI, 10% to 38%) who received BUCY-2 plus melphalan 90 mg/m2 conditioning developed grade greater than or equal to 3 RRT; three of these patients (8%; 95% CI, 3% to 25%) died of RRT. Although limited by the relatively small number of patients, our analysis of the patients receiving this regimen showed that the presence of parameters denoting the lymphoid diagnostic group (ie, ALL, NHL, and MM), more extensive pretreatment, and/or more advanced disease status were associated with a higher incidence of grade greater than or equal to 3 RRT. Response data on the AML, ALL, and NHL patients who received BUCY-2 plus melphalan 90 mg/m2 were analyzed: three patients (all with AML in first or second remission) are leukemia-free at 3.0, 2.8, and 1.4 years after AuBMT. The actuarial 2-year event-free survival in this group is 17% (95% CI, 5% to 54%). Response data on the MM and CML patients will be reported subsequently. BUCY-2 plus melphalan at a dose of 90 mg/m2 before AuBMT produces acceptable toxicity in patients who are not heavily pretreated. A full evaluation of the antineoplastic effects of this regimen requires further study.     

High-dose melphalan with autologous marrow for treatment of advanced neuroblastoma.

A group of 12 children with advanced neuroblastoma (7 Stage IV and 5 Stage III), selected by their initial response to chemotherapy with pulsed cyclophosphamide/vincristine/Adriamycin (CVA), were given consolidation therapy with high-dose melphalan (140 mg/m2) and then surgical removal of residual disease. Twenty-two high-dose melphalan procedures were combined with autologous marrow grafting to offset myelotoxicity and were well tolerated. In each of 2 additional children, procedures carried out without marrow autografting led to serious marrow and mucosal toxicity. There were no treatment-related deaths. In 7/11 patients with evaluable computerized tomographic (CT) scans there was a decrease in maximum diameter of the primary tumour after melphalan. Complete response was achieved in 6 patients, of whom 3 are well and have no evidence of disease at 35, 33 and 18 months from completion of all treatment; however, although survival (median 23 months) of all 12 autografted patients is longer than that of 28 comparable children treated between 1970-77 with conventional chemotherapy (median 14 months) the difference is not statistically significant. High-dose melphalan is a safe and tolerable treatment in children when combined with autologous marrow grafting, but further study is required to determine whether the procedure can improve prognosis for patients with advanced neuroblastoma.     

High-dose busulfan and cyclophosphamide with autologous bone marrow transplantation support in advanced malignancies in children: a phase II study

Twenty children with advanced, nonleukemic malignancies entered a phase II study of high-dose busulfan-cyclophosphamide followed by bone marrow transplantation (BMT). All had disease refractory to conventional and/or high-dose chemotherapy (HDC). There were ten neuroblastoma patients, six non-Hodgkin's lymphoma, three Ewing's sarcoma, and one rhabdomyosarcoma. Eight had primarily resistant disease, ten were in second progressive relapse, and two in third progressive relapse. One patient was not evaluable for response. Among the 19 evaluable patients the responses observed were complete response (CR), seven; partial response (PR), three; objective effect, five; and failure, four. However, survival was poor: 15 patients died, two are alive with disease, and three are alive with no evidence of disease (NED) at 8+, 11+, 14+ months post-BMT. Toxicity was high but considered as acceptable, taking into account the terminal state of these patients. Seven treatment-related deaths were observed. This combination therapy proved to be highly effective, with a response rate of 50%, and its value for eradication of residual disease in less advanced patients should be investigated.     

High-dose intensification therapy with autologous bone marrow support for limited small-cell bronchogenic carcinoma

The efficacy and toxicity of high-dose chemotherapy with autologous bone marrow transplantation (ABMT) was studied in 32 patients with untreated limited small-cell bronchogenic carcinoma (SCBC). Ten patients received three courses of induction therapy consisting of vincristine (VCR) (1.5 mg X 2), ifosfamide (5 g/m2), and Adriamycin (Ad; Adria Laboratories, Columbus, Ohio) (60 mg/m2). Patients then received two courses of intensification therapy with cyclophosphamide (CYT) (4.5 g/m2), 4' demethyl-epipodophyllotoxin-d-D-ethylidene glucoside (VP-16-213) (600 mg/m2) and VCR (2 mg) with ABMT. Another 22 patients received induction therapy with VCR, CYT (600 mg/m2), Ad (50 mg/m2), and VP-16-213 (180 mg/m2). All 22 patients also received intensification therapy of the same dose of CYT (4.5 g/m2) and VP-16-213 (600 mg/m2). Nine patients also received high-dose methotrexate (MTX), four patients received Ad (40 to 60 mg/m2), and two patients received both Ad and MTX. After intensification, patients received elective prophylactic brain irradiation (3,000 rad) and chest irradiation (5,000 rad). After induction therapy, there were 13 (41%) complete remissions (CR) and 17 (53%) partial remissions (PR). After intensification therapy, there were 22 CRs (69%) and 10 PRs (31%). Median survival for all patients was 14 months (range, 5 to 59+). Of the 13 patients who received intensification therapy in CR, five remain disease free (DF), four for 4 years or longer. Of the nine patients to achieve CR with intensification, only one is DF. No patient died during intensification. In conclusion, intensification with high-dose chemotherapy can increase the CR rate, and this approach is most likely to show long-term benefits in patients with minimal disease (CR) at the beginning of intensification therapy.     

High-dose combination alkylating agent therapy with autologous bone marrow rescue for refractory solid tumors

Twenty-six adults, ages 27 to 60, with refractory metastatic solid tumors were treated with high-dose cyclophosphamide (Cy) + carmustine (BCNU) at one of three escalating dose schedules followed by autologous bone marrow transplantation (ABMT). Toxicity was severe and dose-related, with the maximum tolerated dose for the combination determined to be Cy 160 mg/kg and BCNU 900 mg/m2. Median time to WBC recovery (greater than or equal to 1,000/microL) was 13 days post-ABMT (range, nine to 22 days) and to a platelet count of greater than or equal to 50,000/microL, 22 days (range, 13 to 83 days). Sixteen of 20 evaluable patients (80%) responded to therapy with at least 50% reduction in measurable tumor, and three patients achieved complete remission (CR). Responders included eight of nine evaluable patients with breast carcinoma, two of five with melanoma, two of two with sarcoma, and four of four with colon carcinoma. Response durations were short (median, 4 months), even for complete responders, and relapses generally occurred at sites of previous metastases. In order for this approach to have a more significant impact on overall survival, it may need to be applied earlier in the natural history of the malignancy.     

High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma.

PURPOSE: We determined the toxicity and efficacy of a new preparative autologous bone marrow transplantation (ABMT) regimen in patients with relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease. PATIENTS AND METHODS: Forty-four non-Hodgkin's lymphoma and 35 Hodgkin's disease patients 16 to 63 years of age were given intravenous carmustine (BCNU) 600 to 1,050 mg/m2, etoposide 2,400 to 3,000 mg/m2, and cisplatin 200 mg/m2 (BEP) and ABMT. Fifty-nine patients also received 15 to 20 Gy local radiation (involved-field radiotherapy [RI]) to active or previously bulky (> 5 cm) disease sites. RESULTS: Nonhematologic toxicities included nausea, vomiting, high-tone hearing loss, stomatitis, esophagitis, diarrhea, and hepatic and pulmonary toxicity. Two patients died within 40 days of marrow infusion as a result of sepsis and one patient died 7 months after transplant as a result of pulmonary fibrosis. Complete remissions (CRs) were noted in 72% (n = 57) of patients (n = 33 non-Hodgkin's lymphoma; n = 24 Hodgkin's disease). Forty patients (51%) remained alive and disease-free (n = 24 non-Hodgkin's lymphoma; n = 16 Hodgkin's disease) at a median of 17 (range, 8 to 57) months after marrow reinfusion. CONCLUSIONS: This regimen seems to be effective for relapsed lymphoma patients whose disease continues to exhibit chemotherapy sensitivity (16 of 24 [67%] disease-free). Furthermore, this regimen seems to be effective in patients who have never attained a CR (seven of 19 [37%] disease-free).     

Impact of autologous bone marrow infusion on hematopoietic recovery after high-dose cyclophosphamide, etoposide, and cisplatin

Because of potential tumor contamination and inadequacy of current purging technique of bone marrow in patients with solid tumors, we investigated an alternative approach to high-dose therapy without autologous bone marrow (ABM) infusion. Three levels of nonmyeloablative doses of cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 165 mg/m2 (CVP) were administered to patients with metastatic solid tumors. Patients were randomized to ABM (n = 46) or no-ABM (NABM) (n = 46) infusion after CVP to study the impact of ABM on hematopoietic recovery, morbidity, and mortality. All patients had ABM harvested, underwent conventional chemotherapy, and then received CVP. Seventy-three patients received two courses of similar doses. The following were the median days to absolute neutrophil count (ANC) of 0.1 x 10(9)/L: for the ABM arm, 19, 21, and 19 and for the NABM arm, 23, 20, and 21 at levels 1, 2, and 3, respectively, during course 1 (P = .01, .80, and .01, respectively). During course 2, ANCs to 0.1 x 10(9)/L and 0.5 x 10(9)/L were attained significantly faster at levels 1 and 3 in the ABM arm. ANC to 1.0 x 10(9)/L was comparable in both arms. Incidence of infection and duration of fever were similar in both arms. Although mortality and the incidence of delayed hematopoietic recovery were more frequent in the NABM arm, this was not statistically significant. Platelet recovery was consistently prolonged in course 2 in both arms, with demonstrable benefit of ABM in course 2 when dose levels were collectively considered. We conclude that (1) ABM enhanced recovery of ANC to 0.1 x 10(9)/L; (2) ABM did not decrease the incidence of infections and the duration of fever; and (3) CVP can be safely given without ABM to carefully selected patients.     

High-dose melphalan and total body irradiation with bone marrow transplantation for refractory malignancies

We investigated if high dose melphalan and total body irradiation could be administered to adult patients with acceptable toxicity. Nineteen adult patients with relapsed disease, 15 of them having hematologic malignancies, were treated with high-dose melphalan (100 mg/m²–140 mg/m²) divided over 2 consecutive days followed by a rest period of 4, days before receiving total body irradiation, 850 rad administered in five fractionated doses over 3, days. Subsequently 11 patients received autologous, seven allogeneic and one syngeneic, bone marrow transplantation. All patients had severe myelosuppression and the major extramedullary toxicity was mucositis. There were three early deaths, two related to septicemia and one to graft-versus-host disease with associated cytomegalovirus pneumonitis. All patients were heavily pretreated, and 16 were demonstrating progressive disease on alternative salvage therapies at the time of bone marrow transplantation. Two of the 16 evaluable patients (12.5%) achieved complete remissions, and 10 (63%) achieved partial remissions for a total response rate of 75%. One patient is a long-term disease-free survivor (over 1 yr). An occasional patient may be cured by this approach. The combination of melphalan, an alternative alkylating agent to cyclophosphamide and total body irradiation are associated with moderate gastrointestinal toxicity in heavily pretreated adult patients. The combination warrants further investigation in a less heavily pretreated population to determine more accurately the complete response rate.     

High-dose cyclophosphamide with autologous marrow transplantation for small cell carcinoma of the bronchus

Summary Twenty-five patients with previously untreated small cell carcinoma of the bronchus have been treated with cyclophosphamide 160–200 mg/kg and subsequent radiotherapy to the primary site. Eighty-four percent of patients responded to the single cycle of chemotherapy, with 56% attaining a complete response. Median duration of remission was 43 weeks and median survival 69 weeks. 2-Mercaptoethane sulphonate was given to prevent urothelial toxicity. Autologous bone marrow transplantation was used to mitigate bone marrow depression but sequential delay in reinfusing cryopreserved bone marrow did not alter the period of cytopenia. Other toxicities were mild. The procedure proved safe and manageable. High-dose chemotherapy may prove to be useful in the initial management of this tumour.     

Treatment of advanced neuroblastoma with high-dose melphalan and autologous bone marrow transplantation

Summary Fifteen children with advanced neuroblastoma according to Evans' classification (1 with stage III and 14 with stage IV) were treated with high-dose melphalan (HDM) followed by autologous bone marrow transplantation. Before HDM, all patients had been extensively treated with multimodality therapy for a median duration of 9 months. At the time of HDM, seven children were in partial remission (PR) with measurable residual tumor and 8 were in complete remission (CR) or good partial remission (GPR). No reduction in measurable tumor size was observed in any of the PR patients. However, when HDM was used as consolidation therapy (CR and GPR patients) survival appeared encouraging, since five of eight patients are alive with no evidence of disease at (NED) 29⁺ to 54⁺ mouths after HDM. Tolerance of this high-dose chemotherapy was satisfactory; gastrointestinal toxicity appeared to be the most important limiting factor. These results suggest that chemotherapy including high-dose melphalan is promising when used as consolidation therapy in patients who have already attained CR with conventional therapies.This study was presented in part at the workshop on high-dose chemotherapy with autologous bone marrow transplant. (Cancer Therapy evaluation program, NCI, Bethesda, March 1984)