Clinics in haematology最新文献

Approximately half of conventional-chemotherapy-resistant, far-advanced Hodgkin's disease patients can be placed into remission with existing intensive therapy regimens and ABMT; these results are similar to those noted in less-heavily pretreated non-Hodgkin's lymphoma patients.

While a few of these end-stage patients have prolonged remissions, failure frequently occurs in a pattern that suggests the inadequacy of the intensive regimens rather than reinoculation of malignant cells in the marrow autograft. The use of additional local radiotherapy may be helpful in selected patients, and more effective regimens may be developed in the future. However, treatment of less advanced disease is primarily indicated.

Due to previous treatment features, patients with advanced Hodgkin's disease may have more morbidity and mortality than a similar group of non-Hodgkin's lymphoma patients. This problem can be minimized by better patient selection, earlier marrow storage and the avoidance of TBI-containing regimens in patients at high risk of interstitial pneumonitis.

Routine marrow purging is unlikely to be required for Hodgkin's disease patients given ABMT.

The use of intensive therapy and ABMT for the treatment of Hodgkin's disease is currently indicated most clearly for treatment of a patient in initial partial remission, early relapse from an, initial chemotherapy-induced remission, or consolidation of a second remission reinduced by conventional therapy.

Massive therapy with ABMT is now an established treatment modality in paediatric oncology. The technical aspects and most treatment-related complications have been clarified and many phase II studies have shown encouraging results. In advanced neuroblastoma the poor outlook with conventional chemotherapy has stimulated extensive investigation of forms of massive therapy. Current results from several centres indicate that although the median survival is increased, long-term survival in an unselected group of stage IV patients is unlikely to exceed 30% with current regimens.

In the future, management of this disease may involve the use of more intensive induction regimens to improve the quality of remission at the time of ABMT, which remains the single most important prognostic factor. Improved purging procedures involve the possible use of double massive therapy regimens and a combination of immunological and chemical treatments. In other paediatric tumours, the relative rarity and limited indications for ABMT make the evaluation of its role more difficult. Preliminary results in advanced rhabdomyosarcoma and Ewing's sarcoma are none the less encouraging and justify further investigation.

The value of purging procedures remains controversial and their assessment has been hampered by the lack of sensitive clonogenic assays to detect residual tumour cells. However, neuroblastoma has provided a useful model for the investigation of physical, immunological and chemical procedures. Massive therapy is expensive, time consuming, and carries a high cost in patient morbidity and stress to the families involved. As with any new treatment, it must be adequately assessed in phase III, randomized studies. the ENSG and SIOP trials are a beginning and the future of massive therapy in the paediatric patient will, we hope, be based on a rigorous and scientific comparison with other treatment modalities.

Burkitt's lymphoma has proved to be a very useful model for the evaluation of both massive therapy regimens and purging techniques. Results from several centres now confirm a number of general principles in relation to the use of ABMT procedures in this tumour. Patients in whom conventional chemotherapy has failed can be cured by massive therapy but this should be limited to those who have responded to salvage regimens or have only achieved first PR. Chemoresistant relapse is unlikely to be cured and the high probability of a transient response does not justify the procedure in such cases. Important ongoing clinical studies include the use of ABMT in first CR for CNS disease or B-cell ALL. Results in allogeneic grafts suggest that current massive therapy regimens are curative in only 20–50% of patients (Appelbaum and Thomas, 1983) and new combinations are, therefore, still required. Phase I and II studies in patients with ‘resistant relapse’ are investigating the use of sequential high-dose alkylating agents and role of TBI.

It is of particular importance to develop effective conventional ‘salvage’ regimens. Recent experience indicates that the combination of high-dose cisplatin and VP 16 is useful; other possibilities include high-dose interferon and high-dose cytarabine. Purging techniques in BL are now at an advanced stage and the combination of immunological and chemical treatments, once of prove efficacy in individual patients at a laboratory level, should be the subject of randomized studies.