Vinblastine, bleomycin, and methotrexate: an effective adjuvant in favorable Hodgkin's disease

Sixty-seven patients with favorable pathologic stage (PS) I and IIA or B or IIIA Hodgkin's disease were randomized to receive subtotal or total lymphoid irradiation (STLI/TLI) alone or involved field irradiation (IF) plus six cycles of a novel adjuvant chemotherapy containing vinblastine, bleomycin, and methotrexate (VBM). With a follow-up from 6 to 72 months (median, 37 months), the actuarial freedom-from-progressive disease (FFP) at 5 years is 70% after STLI/TLI and 95% after IF plus VBM. One death has occurred in the irradiation-only treatment group. The data for IF plus VBM are significantly superior to previous actuarial results at 5 years using IF alone (FFP = 35%, P less than .00001) and compare favorably with prior results with IF plus nitrogen mustard, vincristine, procarbazine, +/- prednisone (MOP[P]) chemotherapy (FFP = 80% at 5 years, P = .10). VBM is well tolerated with greater than 90% of calculated doses delivered. As anticipated, VBM has had relatively little adverse effect on male or female fertility. Selected pulmonary functions are reduced early after IF plus VBM to a greater degree than with irradiation of the mediastinum alone, but the differences are modest. Based upon our current numbers and follow-up, we can be 90% confident that VBM as an adjuvant to irradiation in favorable Hodgkin's disease is as effective, or even superior, to MOP(P) chemotherapy. Because of its lesser toxicity, adjuvant VBM may have a broader role in the management of Hodgkin's disease.     

Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease.

PURPOSE: The management of early-stage Hodgkin's disease in the United States is controversial. To evaluate whether staging laparotomy could be safely avoided in early-stage Hodgkin's disease and whether chemotherapy should be a part of the treatment of nonlaparotomy staged patients, a phase III intergroup trial was performed. PATIENTS AND METHODS: Three hundred forty-eight patients with clinical stage IA to IIA supradiaphragmatic Hodgkin's disease were randomized without staging laparotomy to treatment with either subtotal lymphoid irradiation (STLI) or combined-modality therapy (CMT) consisting of three cycles of doxorubicin and vinblastine followed by STLI. RESULTS: The study was closed at the second, planned, interim analysis because of a markedly superior failure-free survival (FFS) rate for patients on the CMT arm (94%) compared with the STLI arm (81%). With a median follow-up of 3.3 years, 10 patients have experienced relapse or died on the chemoradiotherapy arm, compared with 34 on the radiotherapy arm (P <.001). Few deaths have occurred on either arm (three deaths on CMT and seven deaths on STLI). Treatment was well tolerated, with only one death on each arm attributed to treatment. CONCLUSION: These results demonstrate that it is possible to obtain a high FFS rate in a large group of stage IA to IIA patients without performing staging laparotomy and that three cycles of chemotherapy plus STLI provide a superior FFS compared with STLI alone. Extended follow-up is necessary to assess freedom from second relapse, overall survival, late toxicities, patterns of treatment failure, and quality of life.     

Early stage infradiaphragmatic Hodgkin's disease: results of radiotherapy and review of the literature.

PURPOSE: To assess the impact of modality therapy on long-term outcome for infradiaphragmatic Hodgkin's disease (IDHD). METHODS AND MATERIALS: During the period 1965-1997, 847 patients with early stage Hodgkin's disease (HD) were evaluated and treated at our institution, 20 of them had IDHD (2.4%). Patients characteristics: stage I, nine patients (five pathological stage (PS), and four clinical stage (CS)) and stage II: 11 patients (six PS and five CS). Two modalities of treatment were used: combined modality (CMT), consisting of chemotherapy followed by extended field radiotherapy or radiotherapy alone (XRT). All patients with CS or PS II, except in one case, were treated with CMT. Overall, 12 patients were treated with CMT and the remaining eight patients were treated with XRT. RESULTS: The relapse rate after initial treatment was 30%. Ten-year disease free survival (DFS) and 10-year cause-specific survival were 60% and 92%, respectively. There was a non-significant trend to a better DFS for the CMT group of patients (76% vs. 35% for the whole series and 100% vs. 24% for stage I patients). The four relapsed patients in the XRT group were inguino-femoral PS I. In four out of the six patients who relapsed (66%) the failure was located solely in the supradiaphragmatic area, outside of the radiation fields. CONCLUSIONS: In our experience, inguino-femoral stage I patients have a high relapse rate after XRT; consequently, CMT consisting of chemotherapy plus involved field radiotherapy should be recommended for early stage HD confined below diaphragm.     

High-dose chemotherapy with autologous bone marrow transplantation in 50 advanced resistant Hodgkin's disease patients: an Italian study group report

Fifty patients with recurrent Hodgkin's disease have been treated with high-dose therapy followed by autologous bone marrow transplantation. Forty-one patients had extranodal sites of relapse and 31 patients had constitutional symptoms. Two patients had been treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), lomustine, vinblastine, procarbazine, and prednisone (CcVPP), and radiation; 16 patients with MOPP, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), radiation, and lomustine, etoposide, and prednisone (CEP); 20 patients with alternating MOPP/ABVD, and 12 patients with alternating MOPP/ABVD followed by CEP and radiation. Eighteen patients had progressive disease during alternating MOPP/ABVD protocol alone or during conventional salvage therapy; 32 patients had had a complete remission with first-line therapy but later relapsed, 25 of them having received conventional salvage therapy; 12 achieved no response or progression ("resistant-relapse" patients); and 13 responded partially or completely ("sensitive-relapse" patients). Complete remission occurred in 24 patients (48%) with a median duration of 24 months and 16 patients (32%) achieved partial response with a median duration of 9 months, for an overall response rate of 80%. Ten patients failed to respond and died in progressive disease 1 to 10 months (median, 6 months) after transplantation. Toxicity was significant including infections (20%), liver enzymes and alkaline phosphatase elevations (100%), and carmustine lung toxicity (7%). There were two treatment-related deaths; one patient died of Pseudomonas aeruginosa septicemia and another patient died of cerebral hemorrhage. These results validate the procedure of high-dose therapy followed by autologous bone marrow transplantation in inducing remission in these advanced, highly-treated patients. Clearly, the question of whether high-dose therapy and transplantation will eventually supersede new conventional salvage therapies will be addressed after controlled clinical studies.     

Stage I to IIB Hodgkin's disease: the combined experience at Stanford University and the Joint Center for Radiation Therapy

The treatment records of 180 patients with pathological stage (PS) IB to IIB Hodgkin's disease treated at Stanford University Medical Center (SUMC) or the Joint Center for Radiation Therapy (JCRT) were reviewed. Pretreatment characteristics were analyzed to assess their influence on survival and freedom from relapse (FFR). The two most important disease characteristics predictive of relapse were the number and type of B symptoms present and the mediastinal mass ratio (MMR). Patients with both fevers and weight loss had a 7-year survival and FFR of only 57% and 48%, respectively. The poor prognosis in this group was apparent for treatment with either radiation (XRT) alone or combined modality therapy (CMT). Patients with night sweats only had no adverse effect of B symptoms on outcome. Patients with a MMR greater than 1/3 had a 7-year FFR of only 58% after XRT, but 79% after CMT (P = .12). The 7-year survivals for these patients were 85% and 88%, respectively. CMT improved the FFR of the entire group of 180 patients when compared with XRT (7-year FFR 86% and 74%, respectively, P = .02); however, survival in the two treatment groups was similar (88% and 89%). Among patients treated with radiation alone, there was a similar survival and FFR irrespective of whether pelvic irradiation was included in the initial treatment fields.     

Salvage radiotherapy in patients with relapsed and refractory Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Lymphoma Study Group.

PURPOSE: To evaluate treatment outcome and prognostic factors in patients with refractory or first relapsed Hodgkin's disease (HD) treated with salvage radiotherapy (SRT) alone. PATIENTS AND METHODS: From 4,754 patients registered in the database of the German Hodgkin Study Group from 1988 to 1999, 624 patients were identified with progressive disease (n = 202), or with early (n = 170) or late (n = 252) relapsed HD. At first treatment failure, SRT alone was given to 100 patients. Patient characteristics were: median age, 36 years; progressive disease, 47%; early relapse, 23%; late relapse, 30%; and "B" symptoms, 14%. Eighty-five percent of the patients relapsed after cyclophosphamide, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP/ABVD) -like regimens; 8% after bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimens, 7% after first-line radiotherapy alone. RESULTS: The volume irradiated was mantle field in 43% of patients, inverted-Y in 8%, total nodal irradiation in 12%, and involved-field in 37%. The median SRT dose was 40 Gy (range, 15 to 50 Gy). Seventy-seven patients achieved a complete remission and four patients achieved a partial remission. The 5-year freedom from treatment failure and overall survival (OS) rates were 28% and 51%, respectively. In multivariate analysis, significant prognostic factors for OS were B symptoms (P = .018) and stage at relapse (P = .014). For freedom from second failure (FF2F) Karnofsky performance status (P = .0001) was significant. In patients with limited stage at progression/relapse, duration of first remission was significant (P = .04) for FF2F. CONCLUSION: SRT offers an effective treatment for selected subsets of patients with relapsed or refractory HD.     

Pathologic stage I and II Hodgkin's disease, 1968--1975: relapse and results of retreatment.

Sixty-seven previously untreated patients with Hodgkin's disease, pathologic stages I and II, seen during a 7-year period were evaluted with respect to initial staging and treatment, as well as relapse and retreatment results. The initial treatment consisted of radiation therapy (RT) to an involved field (IF) or an extended field (EF) for patients with stages IA and IIA, or RT and, in recent cases, combination chemotherapy [cyclophosphamide, Oncovin, procarbazine, and prednisone (COPP)] for patients with stages IB and IIB. Nineteen of the 67 patients relapsed (28%), including 11 of 56 patients with stages IA and IIA (20%) and 8 of 11 patients with stages IB and IIB (73%). Seventeen of the 19 relapses occurred within 24 months after completion of the initial therapy (89%). The relapse-free survival at 5 years was 75% for the A patients and 25% for the B patients. The actuarial survival of stage IA and stage IIA patients at 5 years was 91%; there was no significant difference between patients treated initially with either IF or EF. The actuarial survival at 5 years for the patients with stages IB and IIB was 88%, as most responded to a second program of induction therapy. No correlation could be found between the pattern of relapse and the initial pathologic stage or the mode of treatment.     

Occurrence of acute nonlymphocytic leukemia in a prospective randomized study of treatment for Hodgkin's disease

In a prospective randomized study of treatment with radiation therapy (RT) or RT followed by chemotherapy (CT) for patients with Hodgkin's disease stages I-III, four patients developed acute nonlymphocytic leukemia (ANLL) during post-treatment follow-up. There was a significant relationship between the intensity of the treatment and the appearance of this complication: no cases of ANLL were observed among the 128 patients treated with involved field (IF) RT, IF RT followed by CT, total nodal RT alone (TNR), or total lymphoid irradiation alone (TLI) after a follow-up from 21 to 126+ months (median follow-up 76 months). In contrast, four of 36 patients treated with extensive RT followed by CT developed ANLL at 17, 63, 72, and 91 months. Three of these patients had received TLI + CT, the fourth one TNR + CT.     

Hodgkin's disease stages IA and IIA. A long-term follow-up study on the gains achieved by modern therapy

One hundred forty-nine supradiaphragmatic Stage IA and IIA Hodgkin's disease (HD) patients treated according to one of two different policies, were analyzed to quantitate the therapeutic gains achieved in recent years. Forty-nine patients were managed according to the pre-1969 policy consisting of mantle radiotherapy (XRT) only without laparotomy staging and without subdiaphragmatic treatment. These cases constitute the old series (OS). Ninety-eight patients after 1969 received staging laparotomy-splenectomy and were treated with total or subtotal nodal irradiation, and in a small number also multiagent chemotherapy (MAC). These patients constitute the new series (NS). All prelaparotomy IA and IIA cases are included in the NS even if they became Stage III at laparotomy. Salvage therapy for relapsing disease differed between the OS and NS. The majority of OS relapsing patients received salvage XRT, while the majority of relapsing NS patients received MAC. The NS and OS patient groups are comparable by pretreatment parameters. There is a large and statistically significant improvement in disease-free survival (DFS) and survival (S) in the NS over the OS. At 13 years the NS group had a DFS of 65% compared to 38% in the OS, and S in the NS was 82% compared to 37% in the OS. The improvement in DFS is almost totally due to the addition of prophylactic periaortic XRT in the NS patients. A striking reversal of relapse patterns for the OS and NS was observed. Periaortic nodal relapse occurred in 37% of the OS patients and accounted for 64% of all relapses, while in the NS this failure pattern occurred in only 2% of all cases. Supradiaphragmatic relapse accounted for 74% of all relapses in the NS. Improved salvage of relapsed patients in the NS further added to the overall gain in survival. Whereas no relapsed patient in the OS achieved long-term survival (14% at 10 years, 0 at 25 years), one-half of NS relapses were salvaged by MAC (54% survival at 10 years from relapse). These data clearly document the striking therapeutic gains in Stage IA and IIA supradiaphragmatic HD resulting from the use of prophylactic periaortic XRT and MAC salvage for relapsing patients.     

Treatment of advanced Hodgkin's disease in pediatric patients.

From 1970 to 1976, twenty patients with stage II E or II B to IV B Hodgkin's disease were treated at Children's Hospital of Philadelphia. Initially, four of the stage II or III patients received planned total nodal irradiation (TNI) alone; three patients developed progressive disease during irradiation, and one relapsed after 18 months. These results with TNI led to the use of combined modality therapy. Sixteen patients (4, stage II E or B; 8, stage III; 4, stage IV) were treated with COPP (cyclophosphamide, Oncovin, prednisone, and procarbazine) and radiation therapy. In 14 patients treatment was started with COPP. Patients with disease below L2 received TNI; the rest received involved field (IF) or extended field (EF) irradiation. No patient treated with combination therapy encountered life-threatening toxicity. Relapse-free survival in 12 stage II or III patients is 100% with a median follow-up of 28 months (range, 24 to 91 months). Only one of four stage IV patients is alive. Combined modality therapy is effective, tolerable therapy for children with stage II B--III Hodgkin's disease. No relapses occurred in 10 patients given less that potentially curative radiation. Smaller radiation fields and lower doses are planned for the future.     

高剂量化放疗联合自体造血干细胞移植治疗霍奇金淋巴瘤11例报告

背景与目的：高剂量化放疗（high dose chemoradiotherapy,HDT)联合自体造血干细胞移植（autologous hemotopoietic stem cell,ASCT)巳成为复发与耐药霍奇金淋巴瘤（HL）患者重要的解救治疗手段之一,但对于初治晚期患者的作用还不明确。本论文的目的是进一步评价HDT联合ASCT在HL综合治疗中的地位,特别是探讨其对于初治晚期具有明显不良预后因素患者的作用。方法：11例复发和具有不良预后因素的晚期HL患者,其中初始9例,复发2例;自体骨髓移植（autologus bone marrow transplantation,ABMT)1例,自体外周血干细胞移植（autologous peripheral bllod stem cell transplantation,APBSCT)10例。诱导治疗后4例完全缓解（CR）,7例部分缓解（PR）。7例采用高剂量化疗联合全身照射（total body irradiation,TBI)或全淋巴结照射（total lymph node irradiation,TLI)/次全淋巴结照射（subtatal lymph node irradiation,STLI)作用预处理方案,4例采用单纯高剂量化疗作为预处理方案。5例患者于移植后进行了原发部位的补量放疗。结果：移植前达CR者为巩固治疗,达PR后移植后2例达CR,1例达PR,4例稳定（SD）;SD者均为骨受侵。中位随访13（1-84）个月,所有患者全部生存。4例无病生存;4例骨受侵者疾病无进展生存;3例复发,其中1例经复发部位放疗后,目前又无瘤生存42个月,另外2例正进一步治疗中;根据寿命表法分析,全组6年累积疾病无进展生存率（progression-free survival,PTS)为55.68%,6年累积总生存率（OS）为100%;初治患者6年PFS为62.5%。移植相关毒性主要为IV度骨髓抑制,未见明显心、肝、肾毒性,无移植相关死亡。结论：HDT联合ASCT是治疗复发和具有不良预后因素的晚期HL的一种值得进一步探讨的方法。     

The role of radiation therapy in the management of stage III follicular lymphomas

Between 1961 and 1982, 66 patients with stage III follicular small cleaved (FSC) and follicular mixed small cleaved and large cell (FM) lymphoma were treated at Stanford University. Treatment consisted of total-lymphoid irradiation (TLI) to a total dose of about 4,000 rad in 61 patients or whole-body irradiation (WBI) followed by boost irradiation to sites of involvement in five patients. In addition, 13 patients treated with TLI received adjuvant chemotherapy, consisting of six cycles of cyclophosphamide, vincristine, and prednisone (CVP). Median follow-up was 9.6 years. Kaplan-Meier actuarial survival at five, ten, and 15 years was 78%, 50%, and 37%, respectively. Freedom from relapse at five and ten years was 60% and 40% with no relapses after ten years. In a prospective randomized study of 16 patients who all underwent staging laparotomy comparing TLI with or without adjuvant chemotherapy with CVP, there was no significant difference in either survival or freedom from relapse between the two groups. Patients with limited stage III disease (without B symptoms, less than five sites of involvement, and maximum size of disease less than 10 cm) had an excellent prognosis with a 15-year survival and freedom from relapse of 100% and 88%, respectively. Radiation therapy may be a potentially curative modality in patients with stage III follicular lymphomas.     

HIGH DOSE CHEMORADIOTHERAPY WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE TREATMENT OF ADVANCED HODGKIN''''s LYMPHOMA: A REPORT OF 11 CASES

High dose therapy (HDT) with autologous hematopoietic stem cell transplantation (ASCT) has become one of the standard salvaged treatments for the Hodgkin抯 Lymphoma (HL) patients with relapsed or resistant disease. But its value for the primary treatment of patients with advanced disease and poor prognostic factors remains indefinite. It is being one of the clinic research directions to select this kind of patients to undergo ASCT treatment in recent years. From May, 1994 to December, 2…     

Analysis of supradiaphragmatic clinical stage I and II Hodgkin's disease treated with radiation alone.

Patients with clinical Stage I and II Hodgkin's disease have been managed at the Princess Margaret Hospital for over 20 years, without the use of routine staging laparotomy. Our experience identified as adverse prognostic factors presence of a large mediastinal mass, B symptoms, and advanced age in presence of unfavorable histology (20). We had suggested previously that the use of extended field radiation therapy (XRT) was associated with a lower risk of relapse than involved field XRT or mantle XRT. There has been a trend over the past decade to select those patients with favorable prognostic factors for treatment with XRT alone and to use mantle plus upper abdominal XRT (extended field XRT) to treat them. A retrospective study of patients with clinical Stage I and II Hodgkin's disease treated at the Princess Margaret Hospital between 1978 and 1986 was conducted to determine the impact of patient selection and extended field radiation on outcome. The study involved 250 patients with supradiaphragmatic disease selected for treatment with radiation alone on the absence of adverse prognostic factors. Radiation techniques included involved field radiation in selected patients (those with upper neck involvement), mantle radiation in the earlier years, and mantle plus upper abdominal radiation in the later years of the study. Actuarial survival was 83.3% at 8 years; cause-specific survival was 90.1% and the relapse-free rate 71.6%. Local tumor control was 94.6%; only two patients had true infield failure. Multivariate analysis showed that significant prognostic factors included age, histology, and erythrocyte sedimentation rate. Extent of the radiation treatment volume was significant and influenced the risk of relapse, particularly out-of-field relapse, independently of other factors. A dose of 35 Gy was found to be sufficient for control of clinical disease. This study validated a previously developed model for the selection of clinically staged patients with Stage I and II Hodgkin's disease for treatment with radiation alone. Careful selection of these patients can yield excellent results without requiring that staging laparotomy be routinely performed or the use of systemic chemotherapy as the initial treatment.     

A randomized study comparing chemotherapy alone with chemotherapy followed by radiotherapy in patients with pathologically staged IIIA Hodgkin's disease

This paper reports the five-year follow-up (range, 1-8 years) of 56 patients with pathologic stage IIIA Hodgkin's disease randomized for chemotherapy alone or chemotherapy followed by radiotherapy to previous areas of disease (26 treated with mustine, vinblastine, procarbazine, and prednisolone [MVPP] alone, 30 with MVPP and radiotherapy). Of the 56 patients 53 (95%) achieved a complete remission with chemotherapy and of these only five (9%) have relapsed; three died of Hodgkin's disease. There was no improvement in relapse-free survival associated with the uses of radiotherapy following chemotherapy but in view of the small numbers of relapses and the excellent results following chemotherapy alone, a significant improvement could not be expected. The use of MVPP alone can be recommended as an alternative therapy for patients with stage IIIA Hodgkin's disease. This avoids both the physical and psychologic morbidity associated with the high relapse rate following extensive primary radiotherapy and the necessity of combined modality treatment for about half these patients. The question of whether radiotherapy should be given to areas of previous bulk following chemotherapy has not yet been answered in this trial which is continuing.     

Combined modality therapy for stage I-II large cell lymphoma

Between January 1978 and December 1986, 94 patients with Stage I-II large cell lymphoma were evaluated at Stanford University Medical Center and treated with a combination of chemotherapy (CTX) and irradiation (XRT). The predominant histology was diffuse large cell (78), followed by immunoblastic (7), follicular large cell (6), and diffuse mixed small and large cell lymphoma (3). Twenty-three patients had Stage I and 71 had Stage II disease. Fifty-one had extranodal involvement (13 IE, 38 IIE), and 11 had B symptoms (2 IB, 9 IIB). Lymphoma was supradiaphragmatic in 58 patients, infradiaphragmatic in 21, and only in extranodal sites in 15. Patients received either involved (81) or extended (13) field XRT with a median dose of 40 Gy and combination CTX with 2 to 9 cycles (median 6) of either CHOP (68), M-BACOD (8), C-MOPP (8), MACOP-B (4), or other (6). Seventy-two patients remain with no evidence of disease, 21 are dead with disease, and one suffered an intercurrent death. Among the 19 patients who relapsed, there were six failures within the XRT field only, two within and outside the XRT field, and 11 outside of the XRT fields only. Actuarial survival and freedom from relapse (FFR) for the entire population were 74% and 72% at 5-years, respectively (33 month median follow-up). Stage I patients achieved 81% survival and 78% FFR, and Stage II patients had 72% survival and 70% FFR. In univariate and multivariate analyses, a favorable outcome was associated with the CTX-XRT-CTX sequence of therapy (p = 0.001), low LDH (p = 0.01), and small tumor bulk (p = 0.04). There were no relapses or deaths among the 21 patients receiving the "sandwich" sequence (CTX-XRT-CTX) of therapy. This series may serve as a comparison with single modality treatment programs for localized large cell lymphoma using either XRT or CTX alone.     

Treatment of advanced-stage massive mediastinal Hodgkin's disease: the case for combined modality treatment

In the initial series of 198 patients treated at the National Cancer Institute (NCI) with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy for Hodgkin's disease, a review of presenting chest radiographs available on 192 of these patients showed 49 patients with mediastinal masses greater than one third the greatest posteroanterior chest diameter. Five patients had stage IIB disease, and 44 had stage III or IV disease. Thirty-five (71%) patients achieved a complete remission with MOPP chemotherapy. Fourteen (40%) of the complete responders relapsed, but four of these achieved durable remissions in response to subsequent therapy. Thirty (61%) patients have died (14 induction failures, nine relapsed patients, seven complete responders in remission). Thus, with a median follow-up of 20 years (range, 15 to 23), the overall survival for the group is 39%, and the disease-free survival for the complete responders is 60%. A subset of 10 patients received mantle radiation therapy after maximal response to MOPP. One of these patients failed to achieve complete remission, but among the nine complete responders only one has relapsed. In contrast, 13 of 26 (50%) patients achieving a complete response to MOPP alone have relapsed (P2 = .0536). Although MOPP alone was not prospectively compared with MOPP plus radiation therapy in the treatment of advanced-stage massive mediastinal Hodgkin's disease in this series, the retrospective analysis shows a nearly significant difference in disease-free survival favoring combined modality treatment. The difference in tumor mortality between MOPP-treated (44%) and combined modality-treated patients (80%) was also nearly significant (P2 = .055). However, overall survival differences between patients treated with MOPP alone and those treated with combined modality therapy were not significantly different (P2 = 0.23) because of the mortality related to late complications of combined modality treatment.     

High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma: long-term follow-up

We previously reported a phase 2 trial of 69 patients with newly diagnosed anaplastic or aggressive oligodendroglioma who were treated with intensive procarbazine, CCNU (lomustine), and vincristine (PCV) followed by high-dose thiotepa with autologous stem cell rescue. This report summarizes the long-term follow-up of the cohort of 39 patients who received high-dose thiotepa with autologous stem cell support. Thirty-nine patients with a median age of 43 (range, 18-67) and a median KPS of 100 (range, 70-100) were treated. Surviving patients now have a median follow-up of 80.5 months (range, 44-142). The median progression-free survival is 78 months, and median overall survival has not been reached. Eighteen patients (46%) have relapsed. Neither histology nor prior low-grade oligodendroglioma correlated with risk of relapse. Persistent nonenhancing tumor at transplant was identified in our initial report as a significant risk factor for relapse; however, long-term follow-up has not confirmed this finding. Long-term neurotoxicity has developed only in those patients whose disease relapsed and required additional therapy; no patient in continuous remission has developed a delayed neurologic injury. This treatment strategy affords long-term disease control to a subset of patients with newly diagnosed anaplastic oligodendroglioma without evidence of delayed neurotoxicity or myelodysplasia.     

Phase I/II trial of total lymphoid irradiation and high-dose chemotherapy with autologous stem-cell transplantation for relapsed and refractory Hodgkin's lymphoma.

BACKGROUND: The standard approach to treatment of relapsed/refractory Hodgkin's lymphoma (HL) is high-dose chemotherapy conditioning followed by autologous hematopoietic stem-cell transplantation (aHSCT). We report the results of a prospective phase I/II clinical trial of accelerated hyperfractionated total lymphoid irradiation (TLI) immediately followed by high-dose chemotherapy for relapsed/refractory HL. PATIENTS AND METHODS: Forty-eight patients underwent aHSCT with either sequential TLI/chemotherapy (n = 32) or chemotherapy-alone conditioning (n = 16), based on prior radiation exposure. The first 22 patients enrolled on trial received escalating doses of etoposide (1600-2100 mg/m(2)) with high-dose carboplatin and cyclophosphamide. RESULTS: No dose-limiting toxicity was seen and TLI/chemotherapy was well tolerated. The 5-year event-free survival (EFS) estimate for all patients was 44% with overall survival (OS) of 48%. Five-year EFS and OS for the TLI/chemotherapy group was 63% and 61%, respectively, compared with 6% and 27%, respectively, for the chemotherapy-alone group (P < 0.0001 and P = 0.04, respectively). Patients with primary induction failure HL who received TLI/chemotherapy had 5-year EFS and OS rate of 83%. The 100-day treatment-related mortality was 4.2% and two secondary cancers were seen. Significant factors predicting survival by multivariate analysis included TLI/chemotherapy conditioning and B symptoms at relapse. CONCLUSIONS: Sequential TLI/chemotherapy conditioning for relapsed/refractory HL is safe and associated with excellent long-term survival rates.     

Phase II trial of high-dose chemotherapy with autologous stem cell transplant for stage IV breast cancer with minimal metastatic disease.

The purpose of this study was to assess the efficacy of high-dose chemotherapy (HDC) with autologous stem cell transplant in stage IV breast cancer patients with minimal metastases. Eligible patients had (a) disease that could be resected en bloc and/or irradiated with curative intent using a single field and could, thus, be rendered as having no evidence of disease (NED); and/or (b) <5% bone marrow involvement. From September 1991 to August 1997, 40 consecutive patients were prospectively entered on the study. Pre-HDC local treatment consisted of surgery (n = 31) and radiotherapy (XRT; n = 3). All patients received HDC with cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea and autologous stem cell transplant, with or without CD34 selection. Following HDC, 22 patients received XRT. Four patients died of treatment-related complications. Eighteen patients developed grade 3 nonhematological toxicities (15 lung, 2 cardiomyopathy, and 1 optic neuritis), which resolved with therapy. Within a median follow-up of 49 (15-91) months, 14 patients had relapsed. Twenty-five patients (62.5%) were alive, and 22 patients (55%) were alive and free of disease. Median event-free and overall survivals were 43 and 77 months, respectively. In the subset of patients with one metastatic site, 17 of 24 (68%) remained relapse free. Grade 2 tumors, a single metastatic site, and delivery of XRT were favorable predictors of relapse-free survival in univariate but not multivariate analyses. Inclusion of HDC, as described, in the multimodal treatment of stage IV breast cancer patients with minimal metastases is promising. These results warrant prospective randomized trials with a HDC-containing arm in this patient population.