Autografting for patients with chronic myeloid leukaemia in chronic phase: peripheral blood stem cells may have a finite capacity for maintaining haemopoiesis

Abstract

We treated 14 patients with Ph-chromosome-positive chronic myeloid leukaemia still in chronic phase by autografting with blood-derived haemopoietic stem cells. Eleven patients were autografted electively after cytoreductive treatment with busulphan (16 mg/kg) and melphalan (60 mg/m2) and three were autografted after marrow cells from HLA-identical sibling donors had failed to engraft. In 13 patients haemopoiesis recovered; one failed to engraft and died 114 d after autografting. Two other patients became pancytopenic and received further stem cell transfusions at 3 and 40 months respectively after first autografting. One patient entered lymphoid transformation and died 14 months after autografting. Twelve patients survive at a median of 41 months (range 24-53) after autografting. Nine of the survivors have required further chemotherapy after autografting and four of the nine were electively autografted on a second occasion. Three patients surviving after autografting for 28, 43 and 53 months respectively have not required further chemotherapy. In two of these patients haemopoiesis is now predominantly Ph-negative. We conclude that autografting in chronic phase might prolong survival in some cases by reducing the size of the leukaemic stem cell population. The fact that initially successful grafts failed in two patients suggests that blood-derived stem cells may have a finite potential for self-replication.

BCR/ABL-negative progenitors are enriched in the adherent fraction of CD34+ cells circulating in the blood of chronic phase chronic myeloid leukemia patients

“…Ph − cells are relatively frequent, coming high-dose therapy and in some cases Ph chromosomepared to mature cell populations, in primitive hemopoietic cell negative recovery has been observed. 10 …”

Residual Ph‐negative stem cells in chronic myeloid leukemia‐sometimes or always?

“…Although this approach cannot be regarded as standard practice for the management of CML in transformation, it was of great interest nevertheless to observe that some patients treated in this way achieved Ph-negative hemopoiesis and that this Ph-negativity could in some cases be maintained for some months [17]. Because of these early observations, it was not entirely unexpected that patients autografted in CP could also achieve Ph-negative hemopoiesis; this condition has been prolonged in a minority of cases [19]. Again, these data provide additional evidence for the conclusion that the blood or marrow of newly diagnosed patients contains a mixture of Ph-positive and Ph-negative cells.…”

Allografting in chronic myelogenous leukemia followed by immunotherapy

“…However, because of the early nature of this clinical trial, much of the data is unavailable at this time. Since a significant number of patients following autografting for CML in chronic phase have a transient partial or complete cytogenetic remission [18], such data will probably become meaningful only after the patients have participated in the study for at least 9-12 months.…”

“…ABMT has been attempted in CML with only limited success [17][18][19][20][21][22], but novel pre-and post-transplant manipulations are being intensively evaluated at this time and have the potential for improving the long-term outcome in these patients [23].…”