Incorporating Marrow Plasma Cell Infiltration at Diagnosis and Cytogenetic Features into Prognostic Scoring at Point of Autologous Stem Cell Transplantation for Multiple Myeloma

240 patients (152 male, 88 female) with a median age of 59 years (27ys–73ys), referred to Hammersmith Hospital, London, for high dose therapy (HDT) and autologous stem cell transplantation (ASCT) between 1994 and 2007 were treated in a uniform fashion with myeloablative doses of Melfalan. The median OS post HDT/ASCT of all patients was 53 months with a median time to disease progression (TTP) of 20 months. In univariate analysis (194 pts) a > 60% plasmacell infiltration of trephine biopsy at presentation was associated with a significantly shorter median TTP (15 months) following HDT/ASCT compared to patients with a lesser degree of marrow plasmocytosis, whose median TTP was 20 months (p=0.003). Studies of chromosomal aberrations were undertaken by metaphase cytogenetics and interphase FISH in 142 pts at the time of ASCT and yielded interpretable results in 96 (67%) pts. Failure of conventional G –banding and FISH was universally due to low plasma cell content of the marrow aspirate below 5% of nucleated cells. 59 pts (42%) did not show any chromosomal abnormalities at point of transplantation; 37 pts (26%) had chromosomal aberrations, involving the IgH gene locus on chromosome 14q32 and/or deletions of the long arm of chromosome 13 (del 13q) in 33 cases. Deletion of the short arm of Chromosome 17 (del 17p) was only seen in one patient. In multivariate analysis (92 pts), independent risk factors for early relapse post ASCT were progressive disease/minimal treatment response at time of transplantation (RR 5.95, 95%CI 2.86–12.57), a plasma cell infiltrate of more than 60% on marrow trephine at diagnosis (RR 3.4, 95% CI 1.68–6.88) and presence of cytogenetic abnormalities other than sole t(11;14) or del 13q (RR 2.04, 95% CI 1.0–4.17) at time of ASCT. An additive scoring model based on these predictive factors (Table 1) identifies a low risk group of 49 pts (score 0) with a median progression free survival (PFS) of 33 months, an intermediate risk group of 34 pts (scores 1–2) with a median PFS of 15.7 months and a high risk group of 9 pts (scores 3–4), whose median PFS is 4.6 months (p<0.0001).

Table 1: Prognostic scoring model

FIG.1:

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Progression free survival in low risk (score 0), intermediate risk (1–2) and high risk (3–4) patients

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Progression free survival in low risk (score 0), intermediate risk (1–2) and high risk (3–4) patients

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