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PubMed2006

[Long-term outcome in patients with symptomatic low-grade oligodendrogliomatous tumors treated by cytotoxic agents].

INTRODUCTION: Whether aggressive treatment or no treatment is the optimal management for low-grade gliomas is controversial. However, symptomatic low-grade gliomas require prompt therapeutic intervention because of neurological impairment, uncontrolled seizures, and deterioration of life quality. METHODS: We report the long-term follow-up, 71 months, of seven patients treated by procarbazine, lomustine and vincristine (PCV) therapy for a symptomatic low-grade oligodendrogliomatous tumor. The mean age at diagnosis was 47 years, the mean time from first symptoms to initiation of PCV therapy was 62 months (range 15-147). RESULTS: All patients initially responded favorably, with improvement of the neurological symptoms and radiological response. Chemotherapy was clinically well tolerated, the main side effect being low hematological toxicity. During the follow-up, no progression was observed in two patients. For the five remaining patients, the time to progression after the PCV induction was 56+/-12 months (range 38 to 73). Four of these patients showed favorable response to a second line of treatment. CONCLUSION: PCV therapy is an interesting therapeutic option for progressively symptomatic low-grade gliomas, even in cases with large tumoral volume. This treatment, of moderate toxicity, improves the quality of life and can result in long-term tumor stabilization.

Adult↗
PubMed2003

New chemotherapy agents in veterinary medicine.

Several anticancer drugs have been added to the therapeutic armamentarium in recent years. Some of these agents are traditional drugs with a long history of use in human oncology. Increased sophistication in clinical trial design in veterinary oncology has allowed the incorporation of agents previously viewed as excessively toxic. Other agents have been developed more recently. This article summarizes the veterinary experience with two older alkylating agents, lomustine and streptozocin, and newer compounds ifosfamide and gemcitabine. The published literature regarding veterinary use of these agents is limited, and the reader is advised to contact a veterinary oncologist for current guidelines when contemplating use of these agents.

Animals↗
PubMed2002

Phase II study of accelerated fractionation radiation therapy with carboplatin followed by PCV chemotherapy for the treatment of anaplastic gliomas.

PURPOSE: To conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with i.v. carboplatin for patients with previously untreated anaplastic gliomas. METHODS AND MATERIALS: Between 1988 and 1992, 90 patients received 1.9-2.0-Gy radiation 3 times a day with 2-h infusions of 33 g/m(2) carboplatin for two 5-day cycles separated by 2 weeks. After radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until the tumor progressed. RESULTS: Ninety patients were evaluable for analysis. Histologically, 69 had anaplastic astrocytoma; 14, anaplastic oligoastrocytoma; and 7, anaplastic oligodendroglioma. Gross total resection was performed in 20 (22%), subtotal resection in 45 (50%), and biopsy in 25 (28%); reoperation (total or subtotal resection) was performed in 50 (56%) patients. A multivariate analysis showed that a younger age (p = 0.026), Karnofsky performance score (KPS; p = 0.009), and brain necrosis (p = 0.0002) were predictive of a better survival. Results from analysis of extent of surgery (biopsy, subtotal resection, gross total resection) approached significance (p = 0.058). Radiation dose, irradiated tumor volume, and techniques used (boost and fields) were not significant variables. The median survival (MS) of all anaplastic glioma patients was 28.1 months; for anaplastic astrocytoma patients, MS was 28.7 months and 40.8 months for the combined anaplastic oligodendroglioma/oligoastrocytoma patients. Long-term survival occurred in 25% of anaplastic glioma patients who were alive 8.6 years after treatment was initiated. Treatment-induced necrosis was documented by surgery or autopsy in 19 (21%) patients; 21 (23%) had a mixed pattern of necrosis and tumor; and an additional 13 (14%) patients who did not have surgical or autopsy demonstration of predominant radiation necrosis had magnetic resonance imaging (MRI) evidence of radiation necrosis. Serious clinical neurologic deterioration and/or dementia requiring full-time caregiver attention were observed in 9 (10%) patients. CONCLUSION: When comparable selection criteria are applied, the rate of MS in this study is inferior to results attainable with current radiation and chemotherapy approaches, although the rates of long-term survival are comparable. Theoretically, patients failing therapy and dying earlier than anticipated may be because of excessive central nervous system (CNS) toxicity resulting from the combination of accelerated fractionated irradiation, intensive carboplatin chemotherapy before each radiation fraction, and postirradiation PCV chemotherapy. On the other hand, patients with treatment-induced necrosis survived significantly longer than patients who did not demonstrate MRI or histologic evidence of necrosis (MS, 106 months vs. 18-33 months).

Adolescent↗
PubMed2002

Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial.

PURPOSE: During adjuvant radiotherapy (RT) for rectal cancer, patients receiving 5-fluorouracil (5-FU) by protracted venous infusion have a higher risk of diarrhea than have patients receiving bolus 5-FU. Toxicity from a previously reported randomized clinical trial was analyzed to quantify the difference in this risk. Additionally, the persistence of diarrhea after RT was analyzed. METHODS AND MATERIALS: A total of 656 patients were eligible. Patients with T3-4 N0-2 M0 or T1-2 N1-2 M0 resected, high-risk rectal cancer were randomly allocated to receive 5-FU by either protracted venous infusion or bolus during RT (50.4-54.0 Gy). Two cycles of bolus 5-FU were given before and after RT. One-half of the first 445 patients were also randomly allocated to receive lomustine in conjunction with the bolus 5-FU. The incidence and severity of diarrhea in relation to patient and treatment characteristics were evaluated. RESULTS: The rate of diarrhea was significantly greater in patients receiving 5-FU by protracted venous infusion than in patients receiving bolus 5-FU; the difference was most pronounced for Grade 3 (severe) diarrhea (21% versus 13%, p = 0.007). The incidence and magnitude of diarrhea before and after RT were similar. Patients treated with an anterior resection had a higher rate of severe or life-threatening diarrhea than did patients treated with an abdominoperineal resection (31% vs. 12%, p < 0.001). CONCLUSIONS: During pelvic RT, patients who receive 5-FU by protracted venous infusion rather than by bolus have a higher risk of severe or life-threatening diarrhea during RT. This risk does not appear to persist during chemotherapy after completion of pelvic RT.

Acute Disease↗
PubMed2003

Spin labeled antioxidants protect bacteria against the toxicity of alkylating antitumor drug CCNU.

We have studied the toxic effect of the alkylating antitumor drug N'-cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU) on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) strains, alone and in presence of oxygen radical-scavenging substances [Vitamin E, stable nitroxyl radical 2,2,6,6-tetramethylpiperidine-N-oxyl (TMPO), and spin labeled (nitroxyl free radical moiety containing) analogues of CCNU] and compared with that of the alkylating antitumor drug 5-(3,3-dimethyltriazene-1-yl)-imidazole-4-carboxamide (dacarbazine, DTIC). All spin labeled compounds tested were almost no toxic at doses of 50-500 microM/ml, whereas the alkylating antitumor drug CCNU showed toxicity in a dose dependent manner. Even low doses of spin labeled nitrosoureas provided protection against the toxicity caused by the antitumor drug CCNU alone. The lowest toxicity against E. coli and S. aureus were achieved when 500 microM/ml of CCNU was combined with 200 microM/ml of spin labeled nitrosourea N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-glycine amid of 2,2,6,6-tetramethyl-4-aminopiperidine-1-oxyl (SLCNUgly). A combination of TMPO with vitamin E completely abolished the toxicity of CCNU. Endogenous formation of oxygen radicals and their possible involvement in CCNU toxicity towards the bacteria strains tested have been also discussed.

Antineoplastic Agents, Alkylating↗
PubMed1998

A retrospective study of the value of chemotherapy as adjuvant therapy to surgery and radiotherapy in grade 3 and 4 gliomas.

The aim of this retrospective study was to evaluate the effect of adjuvant chemotherapy among patients < 55 years of age with anaplastic gliomas (historical grade 3, n = 85) with four cycles 4 weeks apart of 160 mg carmustine (BCNU) infused into the internal carotid artery, combined with vincristine 2 mg and procarbazine 50 mg x 3 for 1 week (i.a.BCNU-PV) versus no adjuvant chemotherapy. In glioblastomas (histological grade 4, n = 257) the same chemotherapy was evaluated versus two cycles 4 weeks apart of 160 mg lomustine (CCNU) orally instead of BCNU, combined with vincristine and procarbazine (PCV) versus no chemotherapy. All patients in both groups received radiotherapy. Among glioblastoma patients < 55 years of age there was a significant (P = 0.03), but moderately increased survival in the i.a.BCNU-PV group versus the two other arms that did not differ from each other. This difference could be explained by an uneven distribution of prognostic factors, especially age group (< 50 years versus 50-54 years) in favour of the i.a.BCNU-PV group. In anaplastic gliomas, the median survival in the i.a.BCNU-PV group was 80 months versus 25 months for the no chemotherapy arm (P = 0.004). No significant differences in the distribution of prognostic factors were found between the two therapy arms. We suggest that the role of adjuvant chemotherapy in glioblastomas is unclear, while i.a.BCNU-PV as adjuvant chemotherapy among patients < 55 years of age and with anaplastic gliomas increased survival markedly.

Administration, Oral↗
PubMed2001

Efficacy and toxicity of a CCNU-containing high-dose chemotherapy regimen followed by autologous hematopoietic cell transplantation in relapsed or refractory Hodgkin's disease.

High-dose CBV (cyclophosphamide, carmustine, and etoposide) in combination with autologous HCT achieves survival rates of approximately 50% at 5 years in recurrent or refractory Hodgkin's disease (HD). However, carmustine (BCNU) dose-dependent pulmonary toxicity occurs in 20% to 30% of patients. A decreased incidence of interstitial pneumonitis as well as a possible benefit in efficacy has been reported with lomustine (CCNU) compared to BCNU in the standard dose setting. In a dose-escalation study, we substituted CCNU for BCNU in the CBV regimen for 16 patients with HD (n = 12) or non-Hodgkin's lymphoma (n = 4). Based on the promising results, an additional 47 consecutive patients with HD were treated with the following regimen: CCNU (15 mg/kg) orally on day -6, etoposide (60 mg/kg) intravenously on day -4, and cyclophosphamide (100 mg/kg) intravenously on day -2. Peripheral blood progenitor cells and/or bone marrow were infused on day 0. With a median follow-up for the surviving patients of 3.2 years (range, 0.8-9.9 years), the 3-year overall survival rate was 57% (CI, +/-15%), event-free survival was 52% (CI, +/-14%), and freedom from progression was 68% (CI, +/-14%). There were 21 deaths, 10 due to HD. Six patients died due to respiratory failure. Interstitial pneumonitis occurred in 63% of patients and could not be correlated with prior chest radiotherapy. This regimen demonstrated survival rates similar to those of historical studies that used the CBV regimen. However, the incidence of interstitial pneumonitis was in excess of expected.

Adolescent↗
PubMed1997

Treatment of pediatric low-grade gliomas with a nitrosourea-based multiagent chemotherapy regimen.

Between March 9, 1984 and January 29, 1992, 42 children with newly diagnosed symptomatic or previously diagnosed progressive low-grade gliomas received outpatient chemotherapy as their primary treatment. This study was a single arm, phase II trial designed to estimate the time to tumor progression and toxicity of this regimen. Procarbazine, 6-thioguanine, and dibromodulcitol were given before lomustine (CCNU) and vincristine was given 1 and 3 weeks after CCNU. Patients were treated for six treatment cycles or until the tumor progressed, whichever came first. Twenty-three patients had juvenile pilocytic astrocytomas, 11 had astrocytomas, one had oligodendroglioma, one had ganglioglioma, and six had radiographically diagnosed low-grade gliomas. The mean age of the patients was 5 years (median, 3 years). The median time to treatment failure was 132 weeks (95% confidence interval: 106, 186 weeks). Only eight patients have died the estimated 5-year survival rate is 78% (95% confidence interval, 60% 87%). There were two episodes of grade 4 neutropenia, and three episodes of grade 4 thrombocytopenia. This regimen was safe, able to be delivered in the outpatient setting, and produced prolonged periods of disease stabilization in children with low-grade gliomas.

Adolescent↗
PubMed2000

Evidence of therapeutic efficacy of CCNU in recurrent choroid plexus papilloma.

A pregnant 33-year old woman developed nystagmus and cerebellar ataxia. A tumor in the roof of the fourth ventricle was diagnosed. The tumor was subtotally removed using microneurosurgical techniques. The histopathological diagnosis was choroid plexus papilloma (CPP). Twenty-one months later, the tumor recurred and was reoperated. Histologically the tumor displayed now increased mitotic activity and pleomorphism. Radiation therapy of the neuroaxis was performed. Within 59 months, the CPP recurred 3 more times with neuroradiological evidence of extensive spinal seeding. After several palliative irradiations, including 2 gamma-knife boosts, the patient was referred to chemotherapy. She was treated with CCNU (Lomustin) 100 mg/m2 orally (12 cycles, cumulative dosis 1440 mg/m2). Within 42 months, there was no new local recurrence and spinal seeding showed significant regression. Clinically the patient improved and stabilized, but needs continuous support because of persisting severe gait ataxia. The course of disease in our patient provides evidence for therapeutic efficacy of CCNU in recurrent CPP.

Adult↗
PubMed2000

Low-dose continuous chemotherapy (LBCMVD-56) for refractory and relapsing lymphoma.

BACKGROUND: Although lymphoid malignancies are generally chemosensitive, relapse is common. The use of high-dose therapy can make subsequent cytotoxic therapy intolerable. There is a need to develop regimens with low acute toxicity which are suitable for use in patients post-high dose therapy and following the failure of standard protocols. PATIENTS AND METHODS: Twenty-six patients with lymphomas, fifteen of whom had received high-dose therapy, were treated with a novel regimen consisting of low-dose lomustine, chlorambucil, daily subcutaneous bleomycin, vincristine and methotrexate with dexamethasone on an eight-week cycle (LBCMVD-56). A median of three cycles was given. RESULTS: The overall response rate at 12 weeks was 67% (21% complete remission (CR)) with a median overall survival of 13 months. A symptomatic response was seen in 72%. Previous high-dose therapy did not compromise the response rate. Toxicity was acceptable with grade 3-4 haematological toxicity seen in 27% of cycles, gastrointestinal toxicity seen in 11% and pulmonary toxicity seen in 8%. Thirty-one percent of patients required hospitalisation at some point during this treatment most commonly for neutropenic sepsis. CONCLUSIONS: LBCMVD-56 is an inexpensive, outpatient-based regimen with low acute toxicity and a high response rate in this heavily pre-treated group of patients.

Adolescent↗
PubMed2002

Concurrent modified PCV chemotherapy and radiotherapy in newly diagnosed grade IV astrocytoma.

UNLABELLED: Adjuvant chemotherapy (CT) in the treatment of grade IV astrocytoma is at best modestly effective. The radiosensitizing effect of CT may confer an advantage to concurrent radiotherapy (RT) and CT. This study investigated concurrent procarbazine, lomustine, and vincristine (PCV) CT in newly diagnosed grade IV astrocytoma patients. METHODS: From 1992 to 1997, patients diagnosed with grade IV astrocytoma (Daumas-Duport criteria), Karnofsky performance score (KPS) > or =70 and age <65 were offered CT. Twenty-seven study patients received concurrent modified PCV plus partial brain RT. Twenty-seven controls treated at the same institution with cranial RT alone were matched for histology, age and KPS. RESULTS: Median age was 49 years and mean KPS was 80 for both groups. Debulking operations were more frequent in study patients than controls (p = 0.034). One-year survival was 70% and 56%, while median survival was 82 weeks and 53 weeks for the study and control groups, respectively (p = 0.1554). CT complications were predominantly hematologic, grades II and III. Two patients developed febrile neutropenia; one patient died from Pneumocystis carinii pneumonia. Nausea, vomiting and allergic reactions were all grade I. CONCLUSION: While a trend to increased survival was seen in the study, patients treated with concurrent PCV CT, this did not reach statistical significance. A phase III trial would help delineate the true effectiveness of concurrent CT in this population. Modified PCV is safe and reasonably well tolerated.

Adult↗
PubMed2003

Combined modality therapy for poorly differentiated gliomas of the posterior fossa in children: a Children's Cancer Group report.

PURPOSE: To study the effectiveness of combined chemotherapy and radiotherapy for children with high-grade astrocytomas of the posterior fossa. PATIENTS AND METHODS: In the CCG-945 study, 250 patients were treated by members of the Children's Cancer Group (CCG). Sixteen children were randomly assigned to one of two chemotherapy regimens, vincristine, lomustine, and prednisone or '8-in-1', using the same involved-field irradiation in both. Six infants received 8-in-1 chemotherapy before involved-field irradiation. All pathologic specimens had central review. RESULTS: Twenty-two patients with an institutional diagnosis high-grade posterior fossa tumors received chemotherapy and/or irradiation. Fifteen were confirmed by central review to have high-grade gliomas. Overall survival for confirmed high-grade astrocytoma of the posterior fossa was approximately 36 +/- 13% at 5 years for the children (n = 11) and 25 +/- 15% at 5 years for the infants (n = 4). CONCLUSIONS: Involved-field irradiation with chemotherapy appeared to prevent extraneural and subarachnoid metastases. We also confirmed the rarity of the tumor (6% of patients registered). Further Phase III trials are necessary to improve survival in this aggressive tumor.

Adolescent↗
PubMed2003

Primary leptomeningeal primitive neuroectodermal tumor.

Leptomeningeal metastases are a common complication of medulloblastomas and other primitive neuroectodermal tumors (PNETs). Much rarer are PNETs apparently arising in the leptomeninges. An 8-year-old boy presented with headache and vomiting, due to neoplastic meningitis from primary neuroectodermal tumor without an identifying mass. After craniospinal irradiation and chemotherapy (carboplatin, vincristine, cyclophosphamide and lomustine) the boy was in remission for 14 months, then suffered several relapses despite various chemotherapy regimens. After the initial presentation of 3.5 years the boy began to suffer from prolonged refractory non-convulsive status epilepticus and later expired from progression of primary leptomeningeal PNET.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Metastatic lung disease to the central nervous system: in vitro response to chemotherapeutic agents.

BACKGROUND: Metastatic lung disease to the central nervous system (CNS) comprises a significant percentage of cranial metastases. For those cases where chemotherapy may be of palliative or therapeutic benefit, in vitro chemoresponse testing may identify the agent(s) most likely to be effective clinically. METHODS: Tumor-derived cell cultures were established from 14 surgically excised lung lesions metastatic to the CNS. In vitro chemoresponse testing was performed with a variety of anticancer agents on the tumor cells that grew out of the cultured tissue specimens. Drug concentrations and exposure times were adjusted to bracket approximate average peak plasma levels that are observed typically in vivo. For each tumor-derived cell culture, a complete dose-response curve was established for each chemotherapeutic agent tested. RESULTS: Approximately 80% of the 14 tumor cell cultures had a definitive response to one or more chemotherapeutic agents in vitro, with approximately one-third of these cultures displaying a response to at least three of the drugs tested. There was considerable heterogeneity in the response of individual tumor cell cultures to the chemotherapeutic drugs. The agents that showed the highest cytotoxic response rate against the individual tumor cell cultures included lomustine, carboplatin, cisplatin and etoposide. CONCLUSIONS: The tumor cells isolated from individuals with lung lesions metastatic to the brain demonstrated differential chemoresponses to the agents tested. No single agent was effective against every tumor cell culture. These data suggest that in vitro chemoresponse testing of cultured tumor cells may be useful to identify biologically effective chemotherapeutic agents for individual patients, thereby addressing at least one factor in this complex therapeutic challenge.

Adenocarcinoma↗
PubMed1986

Chemotherapy versus chemotherapy plus irradiation in limited small cell lung cancer. Results of a controlled trial with 5 years follow-up.

One hundred and forty-five patients with limited stage small cell lung cancer were included in a randomized trial to evaluate the effect of chemotherapy with or without chest irradiation. Seventy-six patients were allotted chemotherapy alone while 69 patients received the same chemotherapy plus radiotherapy, 40 Gy in split-course, administered in weeks 6 and 10 after the initiation of chemotherapy. The chemotherapy consisted of lomustine, cyclophosphamide, vincristine and methotrexate. Patients treated with chemotherapy alone survived for a median of 52 weeks compared to 44 weeks in patients receiving the combined regimen (P = 0.055). After exclusion of five early deaths and one patient refusing the irradiation plus 14 completely resected patients, the remaining 65 patients receiving chemotherapy alone and the 60 patients treated with chemotherapy plus radiotherapy were included in a new analysis. The difference in survival duration which could be ascribed to treatment with or without chest irradiation thereby diminished (P = 0.24). Eighteen months' disease-free survival was obtained in 9.2% of the 65 patients and in 9.8% of the 60 patients. The complete remission rates were 37% and 46%, respectively, (P = 0.33) and the median durations of complete remission were 40 weeks and 52 weeks (P = 0.67). Treatment failure of the primary tumour occurred in 85% of patients treated with chemotherapy alone in contrast to 61% of patients receiving the combined regimen (P = 0.005). Seventy-nine of these patients underwent autopsy at which no residual chest disease was observed in 17% and 37%, respectively (P = 0.045). The combined regimen was more toxic than chemotherapy alone resulting in significantly greater dose reductions and more pronounced thrombocytopenia. Lung and pericardial fibrosis was responsible for four deaths among the complete responders in the radiotherapy group. The combined regimen thus tended to be more efficacious with respect to tumour control at the expense, however, of increased toxicity which per se, eliminated a potential improvement of the overall therapeutical results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Association between chemotherapy response and rate of disease progression in disseminated melanoma.

Fifty-five evaluable patients with disseminated malignant melanoma were treated with the combination of dacarbazine (DTIC) 400 mg i.v. on days 1 to 3 and lomustine (CCNU) 50 to 80 mg m-2 orally on day 1 with intervals of 6 weeks as the first line chemotherapy. Three (5%) patients had complete and 6 (11%) partial response, and 7 (13%) patients had stable disease at least for 3 months. The patients with an objective response (n = 9) survived longer than the rest of the patients if the length of survival was calculated from the start of chemotherapy (P = 0.0006). However, the responding patients also had longer time interval from the diagnosis to the detection of distant metastases (P = 0.05), and survival time from disease progression following DTIC and CCNU therapy (P = 0.005). These findings suggest that patients with an objective response to DTIC-CCNU therapy have melanoma with a slow progression rate, and prolonged survival in such patients may in part result from the less aggressive biological nature of their tumours.

Adult↗
PubMed1993

Depletion of O6-alkylguanine-DNA alkyltransferase correlates with potentiation of temozolomide and CCNU toxicity in human tumour cells.

Temozolomide (8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4-(3H)-one) has shown promising activity in Phase I trials against some brain (glioma) and skin (melanoma, mycosis fungoides) cancers. Temozolomide and lomustine (CCNU) showed parallel toxicity in seven human tumour cell lines and this generally correlated (correlation coefficients 0.87 and 0.92 respectively) with the level of expression of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase, EC 2.1.1.63). Pretreating cells with the ATase inhibitor, O6-benzylguanine (BG), potentiated cytotoxicity to a similar degree with both drugs, but did not sensitise a cell line (ZR-75-1) expressing very low levels of this protein. When BG pretreatment was combined with repeat doses of temozolomide a dramatic potentiation (300 fold) was seen in MAWI cells, which express high levels of ATase, but not in a cell line (U373) expressing lower levels of ATase. [14C]-labelled temozolomide uptake was similar in sensitive and resistant lines. Human ATase-cDNA transfected xeroderma pigmentosum (XP) fibroblasts were more resistant than XP control cells to temozolomide and the related chloroethylating agent mitozolomide and although BG completely suppressed ATase activity in these cells, resistance was still greater than in control cells.

Antineoplastic Agents↗
PubMed1999

High-dose BEAM chemotherapy with autologous haemopoietic stem cell transplantation for Hodgkin's disease is unlikely to be associated with a major increased risk of secondary MDS/AML.

Hodgkin's disease is curable in the majority of patients, although a proportion of patients are resistant to or relapse after initial therapy. High-dose therapy with autologous stem cell support has become the standard salvage therapy for patients failing chemotherapy, but there have been reports of a high incidence of myelodysplasia/acute myeloid leukaemia (MDS/AML) following such treatment. Patients who receive such therapy form a selected group, however, who have already been subjected to other leukaemogenic factors, such as treatment with alkylating agents. In order to ascertain the true risk of MDS/AML, comparison must be made with other patients subjected to the same risks but not undergoing transplantation. We report a retrospective comparative study of 4576 patients with Hodgkin's disease from the BNLI and UCLH Hodgkin's databases, which includes 595 patients who have received a transplant. Statistical analysis including Cox's proportional hazards multivariate regression model with time-dependent covariates was employed. This analysis reveals that the risk of developing MDS/AML was dominated by three factors, namely quantity of prior therapy (relative risk [RR] 2.01, 95% confidence intervals [CI] 1.49-2.71, for each treatment block, P < 0.0001) and whether the patient had been exposed to MOPP (RR 3.61, 95% CI 1.64-7.95, P = 0.0009) or lomustine chemotherapy (RR 4.53, 95% CI 1.96-10.44, P = 0.001). Following adjustment for these factors in the multivariate model the relative risk associated with transplantation was 1.83 (95% CI 0.66-5.11, P = 0.25). This study provides no evidence of a significantly increased risk of MDS/AML associated with BEAM therapy and autologous transplantation in Hodgkin's disease. Concern over MDS/AML should not mitigate against the timely use of this treatment modality.

Acute Disease↗