Multiple myeloma as the first manifestation of acquired immunodeficiency syndrome: a case report and review of the literature.

Various hematologic malignancies and solid tumors are increasingly diagnosed in patients with human immunodeficiency virus (HIV) infection and may be the presenting manifestation of acquired immunodeficiency syndrome (AIDS). Multiple myeloma, however, has never been reported as the presenting manifestation of AIDS. We report on a 34-year-old man who presented with back pain, paresthesias, paraparesis, vertebral bony disease, and an associated soft tissue mass. Biopsy of the mass revealed immature plasmacytes with very faint cytoplasmic expression of kappa light chains. Bone marrow biopsy revealed 25% infiltration with poorly characterized malignant cells and 15% polyclonal plasma cells. Immunofixation of serum and urine was positive for IgG kappa and kappa light chains, respectively. A bone survey revealed lesions in the skull, left femur bone, and the pelvis. The diagnosis of an anaplastic myeloma was made. Because of the poorly characterized nature of the malignant cells and the difficulties in immunophenotyping, serologic evaluation for HIV was undertaken and was positive. The concept of myeloma as an opportunistic neoplasm defining AIDS was considered. We discuss this view and recommend that patients with multiple myeloma with poorly characterized myeloma cells as well as difficulties in immunophenotyping should undergo testing for HIV infection.

Evaluation of argyrophilic nucleolar organiser regions (AgNORs) in multiple myeloma.

AIM: To investigate the prognostic value of argyrophylic nucleolar organiser regions (AgNORs) in multiple myeloma. METHODS: Bone marrow aspirates from 55 newly diagnosed patients with multiple myeloma were stained with the one step AgNO3 technique. The mean number of AgNORs in each plasma cell nucleus (AgNOR count) was tested for a possible correlation with other clinical and laboratory variables at presentation (clinical stage, substage, heavy and light chain isotype, haemoglobin concentration, platelet count, marrow infiltration rate, degree of skeletal lesions, M protein concentration, plasma cell morphology, and serum concentrations of calcium, albumin, lactate dehydrogenase, C reactive protein, and beta 2 microglobulin) and with outcome (response to first line treatment, first remission duration, and overall survival). RESULTS: A significant association between mean (SD) AgNOR count was found only for clinical stage (stage I, 3.09 (1.19); stage II, 3.80 (1.53); stage III, 5.28 (1.79); p < 0.005) and, from all stage determinants, only for M protein concentration (high, 5.92 (1.80); low, 4.01 (1.92); p < 0.001). There was a linear relation between AgNOR count and serum M protein concentration for patients with both IgG (r = 0.450; p < 0.01) and IgA (r = 0.768; p < 0.002) producing multiple myeloma. CONCLUSIONS: Unlike previous investigations, no clear prognostic value for the AgNOR count was found in multiple myeloma. Instead, the results indicate that the AgNOR count might be an index for M protein synthesis rate. This is consistent with other findings in tissues with low proliferative potential and high protein synthetic activity, and calls for a cautious interpretation of AgNORs in malignancies with similar features.

Serum transforming growth factor-beta 1 is related to the degree of immunoparesis in patients with multiple myeloma.

The expansion of myeloma cells is regulated by cytokines, among which IL-6 is a major growth factor. It has been recently suggested that serum transforming growth factor beta 1 (TGF beta 1), a cytokine found in large amounts in alpha-granules of platelets, might play a role in multiple myeloma (MM). It was the purpose of this study to determine serum TGF beta 1 levels in MM patients and to seek a correlation with disease parameters. Measurements were done by ELISA. We studied 35 MM patients (19 stage II, 16 stage III, 20 IgG, 8 IgA and 6 BJ, 1 IgD) in different phases of the disease, 27 healthy individuals and 17 thrombocytopenic patients with other haematological diseases (three MDS, three congenital thrombocytopenia, 11 ITP). Overall samples from MM patients were included: 10 at diagnosis, 18 in remission and 32 in relapse. In normal controls TGF beta 1 serum levels ranged from 1 to 33 ng/ml (median 16.5 ng/ml). In both thrombocytopenic controls with other diseases and thrombocytopenic MM patients (seven samples), TGF beta 1 serum levels were very low (median 3.2 and 4.5 ng/ml respectively). In MM patients with PLT > 100 x 10(9)/L (53 samples), TGF beta 1 serum levels were in the normal range in patients without immunoparesis (1 to 27 ng/ml, median 16.6 ng/ml), whereas they were higher in patients with immunoparesis (polyclonal immunoglobulins (Igs) below lower normal reference values) ranging from 10.2 to 45 ng/ml (median 26.8 ng/ml) (P < 0.01). Serum TGF beta 1 levels fluctuated in the same patient at different times but not according to relapse or remission. Correlation was found only between serum TGF beta 1 levels and immunoparesis and not between serum TGF beta 1 levels and disease stage or Ig subtype nor with prognostic factors for MM (serum CRP, beta 2M or IL-6). This finding suggests that the remaining normal plasma cells are sensitive to the inhibitory action of TGF beta 1 on Ig production. In conclusion TGF beta 1 serum levels are very low in thrombocytopenic patients confirming that platelets are the major source of this cytokine. Furthermore, a strong correlation was found between TGF beta 1 serum levels and immunoparesis in MM patients.

Predictive factors affecting mobilization and peripheral blood stem cell (PBSC) collection using single apheresis (SA) for rescuing patients after high-dose chemotherapy (HD.CHE) in various malignancies.

We have investigated factors that affect the efficiency of single apheresis (SA) before transplant and define groups of patients that may require more than one collection for hematologic support. A consecutive series of 56 patients with hematologic malignancies and solid tumours had peripheral blood stem cells (PBSC) collected following mobilization with colony-stimulating factors (CSF) alone or after conventional chemotherapy (CHE) or high-dose cytoxan (HD.CY) followed by CSF. The efficiency of SA was assessed by total mononuclear cell number (MNC) in the harvest, CD34+ cells and colony-forming units (CFU). Linear regression analysis was performed to determine factors that affect SA yield as assessed by the above parameters. Thirty-five patients were mobilized once, 13 patients twice, six patients required three, one required four and one required five aphereses. Suboptimal mobilization and collection by SA occurred in patients with extended previous radiotherapy (RT) and patients older than 50 years. The number of CHE cycles given in the past also had an adverse effect on SA efficiency. In contrast, disease status, bone marrow infiltration by malignant cells, type of CHE, time since last CHE and mobilization regimen used were not significantly related to the collection efficiency by SA. Age, extent of previous RT and amount of CHE given prior to mobilization define the patients who require more than one SA course for support regardless of the underlying disease, BM status or mobilization regimen used. In such patients a plan for multiple aphereses should be scheduled in advance.

Soluble interleukin-6 receptor (sIL-6R), a new prognostic factor in multiple myeloma.

sIL-6R is a 55 kD soluble molecule mediating the interleukin-6 (IL-6) signal through the IL-6 receptor-associated transmembrane signal transducer, gp130. It has recently been suggested that sIL-6R serum levels may reflect disease severity in multiple myeloma (MM). We determined sIL-6R serum levels in 25 normal controls (NC) and in 80 MM patients at diagnosis and during the course of the disease. Measurements were done by ELISA. In NC, sIL-6R levels ranged from 14 to 40 ng/ml (median 28 ng/ml) whereas in MM patients the range was 10-200 ng/ml (median 38 ng/ml) (P<0.01). 61 patients entered remission and 19 were resistant. Median sIL-6R value at diagnosis was 36 ng/ml (10-120) in responding patients, and 82 ng/ml (20-200) in non-responding patients (P<0.001). During a follow-up from 12 to 89 months, sIL-6R values remained more or less stable in most patients. High sIL-6R levels correlated with poor survival.

Serum interleukin-6 (IL-6) and interleukin-4 (IL-4) in patients with multiple myeloma (MM).

In this study we determined, in patients with multiple myeloma (MM), serum levels of IL-4 and IL-6 at diagnosis and during the course of the disease, seeking a correlation with disease activity and prognosis. We studied 54 MM patients, 41 of whom responded to chemotherapy whilst 11 were resistant. At diagnosis, IL-6 was increased in 66% of patients (median 35.5 pg/ml) whereas IL-4 was low (median 4 pg/ml) in 75% of patients. In responding patients, IL-4 increased in remission (median 25 pg/ml), whereas IL-6 decreased (median 4 pg/ml). In chemotherapy-resistant patients, IL-6 and IL-4 values remained stable during the course of the disease.

An unusual cytogenetic abnormality involving chromosomes 1 and 7 in a case of chronic myelomonocytic leukemia.

We report a case of chronic myelomonocytic leukemia in which cytogenetic analysis revealed a 47,XY, +1, +der(7)del(7)(q32q36)ins(7;1)(q32;p36.3p22) chromosomal constitution. This abnormal karyotype, which as a whole is new to any myeloid malignancy, points to a possible pathogenetic role for the oncogenes MET and FGR on the derivative chromosome 7, and for the CSF1 and JUN genes flanking the breakpoint on chromosome 1.

Recurrence of acute leukemia in donor cells after bone marrow transplantation: documentation by in situ DNA hybridization.

Donor cell leukemia after BMT has been documented in a small number of cases mainly by cytogenetic studies. We describe a case of leukemia relapse in a 16-year-old girl 1 year after BMT from her histocompatible brother. Relapse in donor cells was initially suspected on the basis of cytogenetic analysis and confirmed by DNA in situ hybridization in blast cells using a Y chromosome-specific probe.

Intermediate dose of intravenous melphalan in advanced multiple myeloma.

Eighteen patients with advanced multiple myeloma resistant to VAD chemotherapy (vincristine, Adriamycin, dexamethasone) were treated with intravenous melphalan in a single-pulse dose of 50-70 mg/m2. Objective response (greater than or equal to 50% reduction of the monoclonal protein) was observed in 9 patients. The median duration of remission in the responding patients was 6 months and the median survival 11.5 months. The main toxicity noted was bone marrow suppression. We conclude that intermediate doses of intravenous melphalan are a useful therapeutic modality in refractory or relapsing myeloma patients.