Friday, June 24, 2011

Has the French trial put an end to ASCT?

The French group has looked at autologous stem cell transplant in CLL It is unusual for transplanters to do a randomized trial so we must take it seriously.

It is a complicated trial. Patients aged between 18 and 65 with Binet stage B or C disease diagnosed according to NCI 1996 guidelines were entered. Exclusions included AIHA, another uncured malignancy, severe concomitant disease, Richter’s syndrome, PLL, impaired renal, hepatic, cardiac or respiratory function or HIV seropositivity.

All patients were first treated with3 monthly courses of mini-CHOP followed by 3 courses of fludarabine. Patients then in CR were randomized between ASCT and observation. Those not in CR were rescued with 1 or 2 cycles of DHAP were then randomized to ASCT or 3 courses of FC. Transplant conditioning was with cyclo/TBI (10 Gy). CRs were determined after a CT scan and with bone marrow lymphocytes counted on an aspirate not a trephine (therefore they missed out on nodular PRs).

There were 105 in the CR group and 94 in the non-CR group. In the former 37 had ASCT and 68 observation (15 failed to mobilize stem cells or refused treatment); in the latter group, 34 had ASCT (7 failed to randomize, and a further 5 defaulted through death, progression or refusal) and 41 FC.

In the CR group the 3 year event-free survival was 79.8% v 35.4% in favour of ASCT. By multivariate analysis unmutated IGHV and del 11q were predictors of poor survival. However, at 3 years there was no difference in overall survival between the two arms. In the non-CR group there was no difference in event-free survival or overall survival. Unmutated IGVH and del 17p were predictors of poor outcome.

Mobilization after the 6 courses of preliminary chemotherapy failed in 40% of cases. Mobilization after mini-CHOP and before the fludarabine failed in only 8.3% of cases. This mirrors previous experience that fludarabine influences stem cell mobilization.

These results are broadly in line with the phase 2 data on ASCT. Do they now show that ASCT should be abandoned? I do not think so. The follow-up is too short to ascertain whether there will be an overall survival advantage. It does suggest that obtaining a CR before ASCT is vital, but this trial was started before rituximab was widely available in France and with it more CRs should be obtained. I suspect that for bulky or extensive CLL with mutated IGHV genes ASCT might still be the best treatment out there

2 comments:

Anonymous said...

Speaking of trials, I am curious as to your thoughts on whether patients should be thanked in journal articles publishing trial results.

Something as simple as:

We would like to thank all the patients in this trial for participating.

Terry Hamblin said...

Absolutely!