Peripheral blood stem cell contamination in mantle cell non-Hodgkin lymphoma: the case for purging?

Abstract

Summary:Intensification using peripheral blood stem cells collected after chemotherapy followed by growth factors is being increasingly investigated as an alternative to conventional chemotherapy for mantle cell non-Hodgkin lymphoma. We investigated 14 grades III-IV, t(11;14)-positive cases for contamination of PBSC collected after a polychemotherapy regimen followed by G-CSF. Patients were first treated with a polychemotherapy regimen. There were four CR, seven PR, two refractory and one early death. Seven patients have been transplanted, in whom PBSC were mobilized, using either cyclophosphamide/VP16 or Dexa-BEAM followed by G-CSF. For all patients, whether actually autografted or not, PB cells were tested at the time of regeneration on G-CSF after the first polychemotherapy or after the mobilizing regimen. PCR evaluation of contamination was performed first by a semi-quantitative approach, using serial dilutions of initial DNA, then confirmed using a limiting-dilution analysis. Two patients were not informative (one early death and one without an available molecular marker). PB cells collected at regeneration contained at least one log more lymphoma cells than steady-state blood or marrow, apart from in two cases. Moreover, where a mobilizing treatment diminished tumor burden in the patient, at the same time it increased PB contamination in most cases. We conclude that advanced mantle cell NHL appears to be largely resistant to significant in vivo purging by conventional chemotherapy. Where treatment brings benefits by reducing tumor load, it may at the same time negate it by mobilizing malignant cells into the collections used to intensify. Although the clonogenic potential of this massive infiltration is unknown (only gene marking studies could provide a definitive answer regarding the source of relapses), strategies aimed at reducing the level of contamination in the graft should be considered when designing future protocols.

Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen)

“…In contrast, the results in Figure 2 show that all 20 informative patients treated with R-HDS yielded very large amounts of CD34 ϩ cells, devoid of mantle cell contamination. Of note, this very high eradication rate was obtained in patients starting with an overt leukemic PB pattern in 57% of the cases and showing (as observed previously by Jacquy et al 25 ), a massive lymphoma-cell mobilization following the initial 3 courses of conventional chemotherapy. These results confirm and extend our original observation 15 that the combination of high-dose chemotherapy and rituximab represents a very effective in vivo purging method in this otherwise hard to purge disease.…”

“…Of note, during the hematologic recovery following the standard-dose induction chemotherapy cycles, these patients showed a marked increase in the number of circulating lymphoma cells at a time when solid tumor masses were shrinking. This chemotherapy-elicited leukemization, already reported by Jacquy et al, 25 was no longer evident after subsequent high-dose chemotherapy cycles. Of the 28 study patients, there was 1 acute in-hospital treatmentrelated death from cardiac arrhythmia and 3 relapses at 9, 13, and 31 months.…”

Comparison of processing four and five times the patients’ blood volume during peripheral blood stem cell collection and analysis of CD34+38– and CD34+49d+ subsets during apheresis

“…The issue of tumor cell contamination has not been studied in this trial but it is well known that tumor cells can be detected in peripheral blood stem cell grafts even in patients with no measurable disease (Jacquy et al 1999;Kruger et al 2001). Kruger and coworkers also demonstrated that the presence or absence of tumor cells in apheresis samples could not be safely predicted by the presence or absence of tumor cells in marrow or blood.…”

Frontline transplantation of autologous CD34+ selected blood cells for advanced mantle cell lymphoma: no evidence of long-term cure: a single centre experience

“…However, our results contribute to the discussion concerning the utility of graft purging in MCL patients. Recently published papers have demonstrated the resistance of MCL cells to both in vivo 10 and ex vivo purging 6 as well as negligible clinical benefit of the latter strategy. 7 Our limited data do not demonstrate the benefits of CD34 + cell selection and are thus in agreement with others testifying that, to date, there is no evidence that purging by any means could significantly influence disease-free survival.…”