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Background aims Peripheral blood progenitor cell (PBPC) autografts with low CD34+ cell content provide inadequate platelet (Plt) and red blood cell (RBC) reconstitution. Repeat collection and bone marrow (BM) harvesting are used in this situation. Minimum cell contents for BM-PBPC combined grafts are undefined. Methods A retrospective analysis of 19 autologous stem cell transplants (ASCT) with combined BM-PBPC for poor initial PBPC collection was carried out. Mobilization was with filgrastim (10 µg/kg/day) alone for 5 days or after chemotherapy. BM was harvested if PBPC collections were CD34+<2.5×106/kg. Results The median age was 55 years (range 19-74). The diagnoses were multiple myeloma (7), non-Hodgkin's lymphoma (7), Hodgkin's disease (4) and acute myeloid leukemia (1). The median cell content (CD34+/kg×106) was 1.1 (0.3-2.7) for BM, 1.2 (0.04-2.8) for PBPC and 2.2 (1.4-4.9) combined. Eight grafts contained <2.0×106 CD34+/kg (1.4-1.8). The median engraftment in days (range) was: absolute neutrophil count (ANC) > 500, 12 (9-39); Plt > 20 000, 25 (15-70); RBC transfusion independence, 17 (6-93). Six patients died of progressive disease (58-293 days post-ASCT), one of infection on day 141 and one of AML on day 11. All patients except one maintained ANC > 1000 without filgrastim support beyond day 19. One patient had cholecystitis and delayed graft failure on day 90. PBPC CD34+ content did not predict CD34+ BM content but correlated with ANC > 500 (r= - 0.64, P=0.003). BM and combined CD34+ and BM TNC/kg did not correlate with engraftment or outcomes. Combined CD34+/kg < or > = 2.0×106 produced similar engraftment and mortality. Conclusions After a failed PBPC collection, BM harvest is a reliable option for obtaining an adequate combined autograft. Combined BM-PBPC autografts with <2.0×106 CD34+/kg can produce satisfactory engraftment. [ABSTRACT FROM AUTHOR]

Summary. Malignant plasma cells generally grow within the bone marrow microenvironment; however, they can also grow at extramedullary sites. To identify the tumour-specific alterations required for extramedullary growth, we analysed the expression profiles of a series of plasma cell neoplasms including primary multiple myeloma (MM), plasma cell leukaemia (PCL) and extramedullary plasmacytoma (EPC). Hierarchical clustering analysis segregated the EPCs from the remaining samples, and revealed an expression pattern associated with angiogenesis in the EPCs, involving higher expression of the genes TIE2, NOTCH3 , CD31 and endoglin. Direct comparison of EPC samples with the MM samples identified 156 genes significantly upregulated and 85 genes significantly downregulated (P < 0·005, t -test) in the EPCs, including several genes involved in angiogenesis and adhesion that were upregulated (including angiopoietin 1, SPARC, Notch3 and fibronectin 1). Immunohistochemical staining demonstrated CD31 and endoglin protein expression in the EPC tumour cells, which are both angiogenesis related and could confer malignant plasma cells with the ability to grow outside the normal bone marrow environment. Defining how malignant plasma cell growth is regulated in the bone marrow versus at extramedullary sites will help to delineate the mechanisms underlying the dependence of tumour cell growth on angiogenesis and cell adhesion. [ABSTRACT FROM AUTHOR]