Intensive chemotherapy for acute non‐lymphoblastic leukemia after primary myelodysplastic syndrome

Abstract

Twenty-five patients with a primary myelodysplastic syndrome (MDS) transformed into acute non-lymphoblastic leukaemia (ANL) were treated with intensive chemotherapy. A complete remission (CR) was obtained in six patients (24 per cent). In five of these six patients two courses of chemotherapy were needed to achieve CR. In eight patients chemotherapy cleared the bone marrow of blasts, but the aplasia was fatal. A partial effect on bone marrow blasts was seen in four patients and no effect in another six. Eleven patients (44 per cent) died from the consequences of chemotherapy-induced cytopenia. A short interval between MDS and transformation into ANL was associated with a better chance of achieving complete remission. Age, karyotype, type of MDS, peripheral blood or bone marrow findings had no influence on the result of chemotherapy. The median survival from start of treatment was 5 months (range 0.5-24 months). In the patients who achieved a CR, the median duration of the remission was 7 months (range 3-12 months). The poor response rate, the short duration of the remissions and the high treatment-related mortality suggest that current intensive anti-leukemic chemotherapy in ANL after primary MDS is of limited benefit.

A prospective study of autologous bone marrow or peripheral blood stem cell transplantation after intensive chemotherapy in myelodysplastic syndromes

“…In this study, results of induction treatment prior to ABMT and APSCT had been similar to those previously reported in the literature in MDS treated with intensive chemotherapy, [8][9][10][11][12][13][14]15,17 ie a relatively low CR rate. Stem cell transplantation could be performed in 62% of patients aged р55 years who achieved CR after intensive chemotherapy, a relatively high figure if compared to the percentage of patients with de novo AML having achieved CR who undergo ABMT in multicenter trials where ABMT is planned for consolidation.…”

“…6,7 Intensive anthracycline AraC chemotherapy, in MDS and AML following MDS, has given lower Correspondence: P Fenaux, Service des Maladies du Sang, CHU, 1 place de Verdun, 59037 Lille, France; Fax: 33 03 20 44 40 94 Received 13 July 1998; accepted 15 January 1999 complete remission (CR) rates than in de novo AML in most published experiences. [8][9][10][11][12][13][14][15] Reasons for the poor response rates to chemotherapy in MDS could include in particular a higher incidence of expression of the multidrug resistance (mdr) gene in MDS than in de novo AML. 16 Recently, our two groups, the Groupe Ouest-Est d'étude des Leucémies aiguës myé-loïdes (Goelams group) and the Groupe Français des Myélo-dysplasies (French MDS group: GFM), found in a randomized study that modulation of mdr expression by quinine improved CR rates obtained with intensive chemotherapy in MDS patients expressing the mdr gene.…”

“…17 Intensive chemotherapy, in MDS and AML following MDS, also gives shorter CR duration than in de novo AML, and a very low proportion of long-term survivors (14% at 4 years in our experience) is observed. [1][2][3]7,8,[8][9][10][11][12][13][14] Therefore, in an attempt to improve long-term outcome, several groups have performed autologous stem cell transplantation, [18][19][20][21] either bone marrow (ABMT) or peripheral stem cell transplantation (APSCT), as consolidation treatment in MDS patients who achieved CR after intensive chemotherapy. Only retrospective studies of ABMT or APSCT have been reported so far.…”

A randomized study of granulocyte colony-stimulating factor applied during and after chemotherapy in patients with poor risk myelodysplastic syndromes: a report from the HOVON Cooperative Group

“…Resistance to chemotherapy has also been argued to be responsible for treatment failure in MDS. 10 It has been assumed that HGFs are capable of reducing the duration of the pancytopenic period after chemotherapy, and therefore reducing infectious morbidity and mortality. In addition it has been argued, based upon preclinical evidence, that hematopoietic growth factors administered simultaneously with chemotherapy might prime the malignant cells to make them more susceptible to cell killing, and thus contribute to overcome drug resistance.…”

“…In addition it has been argued, based upon preclinical evidence, that hematopoietic growth factors administered simultaneously with chemotherapy might prime the malignant cells to make them more susceptible to cell killing, and thus contribute to overcome drug resistance. 10,11 Here we present the results of a randomized study which addressed the question as to whether the addition of G-CSF to remission induction chemotherapy might improve the hematopoietic recovery and response to chemotherapy and reduce the frequency and severity of infectious complications.…”