A comparison of vincristine and doxorubicin infusional chemotherapy with methylprednisolone (VAMP) with the addition of weekly cyclophosphamide (C-VAMP) as induction treatment followed by autografting in previously untreated myeloma

In a sequential nonrandomized study, 204 consecutive unselected patients aged < 70 years received induction chemotherapy with infusional vincristine and adriamycin with oral methyl prednisolone (VAMP; n =75) or with additional cyclophosphamide, C-VAMP ( n =129). 38/129 C-VAMP patients also received verapamil during induction as part of a controlled trial with the aim to overcome drug resistance. A median of five courses (range 1–11) of chemotherapy were required before maximal response was attained and this was similar in both groups. An over-all response rate of 71% was noted at the end of induction. The complete remission (CR) rate with C-VAMP was 24%, which was significantly higher ( P =0.04) than the CR rate with VAMP alone (8%). The addition of verapamil did not alter the response rate of C-VAMP. Compliance to VAMP was overall 83% and not affected by the addition of cyclophosphamide. The proportion of patients going on to receive high-dose chemotherapy and an autograft was the same for VAMP and C-VAMP treated patients (71%). The median overall survival (OS) and progression-free survival (PFS) for the whole group were 4.4 years and 2.0 years and no difference in outcome was observed between the different treatment groups. Therefore the addition of weekly cyclophosphamide to VAMP induction therapy has significantly improved the response rates of previously untreated myeloma patients. C-VAMP was not more toxic and did not compromise the chances of receiving an autograft. Verapamil was without influence on any parameters in this study.     

Additional chromosome abnormalities confer worse prognosis in acute promyelocytic leukaemia

Acute promyelocytic leukaemia (APL) has been associated with a favourable prognosis in many studies of acute myeloid leukaemia. A series of 54 patients treated at the Royal Marsden Hospital between 1979 and 1996, with APL and the t(15;17) chromosome translocation at pres-entation, was examined for the effect of additional chromosome abnormalities in their presentation karyotype on survival.
The patients were aged between 2 and 62 years with a median age of 31 years. There were approximately equal numbers of males and females. Presentation white cell count ranged from 0.7 to 156 × 10⁹/l with a median of 1.0 × 10⁹/l. 39% of patients (21/54) had additional chromosome abnormalities at presentation. Statistical analyses were performed for factors thought to influence survival such as age, sex, white cell count, and number of courses of chemotherapy required to enter remission. These showed that the presence of additional chromosome abnormalities has an adverse effect on prognosis, independent of other prognostic indicators, reducing it to the level of patients with AML from less-favourable cytogenetic subgroups. These data indicate that additional therapeutic strategies may be required in patients with APL who demonstrate cytogenetic aberrations over and above the t(15;17) at presentation. The biological basis for the more aggressive nature of these cases remains to be determined.