National Cancer Institute®
Last Modified: January 1, 2002
UI - 11436102
AU - Huijgens PC; Dekker-Van Roessel HM; Jonkhoff AR; Admiraal GC; Zweegman
TI - S; Schuurhuis GJ; Ossenkoppele GJ High-dose melphalan with G-CSF-stimulated whole blood rescue followed by stem cell harvesting and busulphan/cyclophosphamide with autologous stem cell transplantation in multiple myeloma.
SO - Bone Marrow Transplant 2001 May;27(9):925-31
AD - Department of Haematology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
In 90 consecutive patients with multiple myeloma, we investigated the feasibility of administering a tandem high-dose therapy regimen, using whole blood for rescue after the first and leucapheresis harvested between the two high doses, for rescue after the second high dose. After 5 days of G-CSF 1 litre of whole blood (WB) was obtained, left undisturbed at 4 degrees C and reinfused 24 h after HDM (140 mg/m(2)). Patients not in progression after 3-6 months were again mobilised, leucapheresed and treated with busulphan 16 mg/kg and cyclophosphamide 120 mg/kg (Bu/Cy) and reinfusion. In 90 patients, WB contained a mean (range) of 0.57 (0.02-3.22) x 10(6)/kg CD34(+) cells. Recovery after HDM was in 13 days for granulocytes and in 18 days for platelets, with 11 patients not recovering within 3 months. There were three toxic deaths. Sixty-six patients qualified for harvesting after HDM. In the first 11, marrow was harvested. The subsequent 55 patients were mobilised and in 45 the preset minimum of 1.5 x 10(6) CD34(+) cells was obtained. Forty-nine patients actually received Bu/Cy. Recovery after Bu/Cy and marrow reinfusion was in 35 days for granulocytes and 20 days for platelets, with two of five patients not recovering after 3 months. After Bu/Cy and leucapheresis reinfusion, recovery was in 17 days for granulocytes and in 34 days for platelets. Nine patients did not recover within 3 months. There were four toxic deaths. The median overall survival from diagnosis for patients receiving HDM was 49 months and for patients also receiving Bu/Cy, 84 months. We conclude that WB rescue after HDM followed by leucapheresis and a second transplant is feasible in the majority of patients. Better mobilisation techniques are required to increase the number of patients who can receive the second transplant.
UI - 11419023
AU - Alyea EP; Anderson KC
TI - Allotransplantation for multiple myeloma.
SO - Cancer J 2001 May-Jun;7(3):166-74
AD - Division of Adult Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02215, USA.
UI - 11433658
AU - Kerst JM; van der Lelie J; Kuijper EJ
TI - [Diarrhea due to Clostridium difficile toxin in hemato-oncological patients]
SO - Ned Tijdschr Geneeskd 2001 Jun 16;145(24):1137-40
AD - Afd. Inwendige Geneeskunde, Academisch Medisch Centrum, Meibergdreef 9, 1105 AZ Amsterdam. email@example.com
In two patients with multiple myeloma, men aged 72 and 54 years, diarrhoea developed upon chemotherapy with vincristin, doxorubicin and dexamethasone (VAD). In the second patient, diarrhoea developed after subsequent peripheral stem cell mobilisation. Pseudomembranous colitis was seen in the first patient during endoscopy but an enzyme immunoassay of the faeces was false negative for Clostridium difficile enterotoxin. The bacterium was later cultured from stool samples and toxins were detected in a repeated immunoassay. Stool samples of the second patient were positive for C. difficile enterotoxin. For both patients an antibiotic treatment resulted in a rapid recovery. In haemato-oncological patients, diarrhoea is often caused by oncolytic therapy. However, consideration should also be given to C. difficile infection as an alternative cause which is easily treatable.
UI - 11441628
AU - Friedman TC
TI - Reflections on going home.
SO - J Palliat Med 2001 Summer;4(2):205-7
AD - Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. firstname.lastname@example.org
UI - 11447701
AU - Paradisi F; Corti G; Cinelli R
TI - Infections in multiple myeloma.
SO - Infect Dis Clin North Am 2001 Jun;15(2):373-84, vii-viii
AD - Clinic of Infectious Diseases, University of Florence School of Medicine, Florence, Italy.
Multiple myeloma is a relatively rare but severe hematologic malignancy. Marked depression in production of normal immunoglobulins, mild neutropenia, and alkylant/steroid therapy or BMT/SCT all produce major suppression of the immune system in the totality of patients. Recurrent bacterial, fungal, and viral infections are an important cause of morbidity and the most common cause of death in these subjects. Prompt diagnosis and appropriate anti-infective chemotherapy are essential in order to reduce the risk of mortality.
UI - 11456228
AU - Stagnaro E; Ramazzotti V; Crosignani P; Fontana A; Masala G; Miligi L;
TI - Nanni O; Neri M; Rodella S; Costantini AS; Tumino R; Vigano C; Vindigni C; Vineis P Smoking and hematolymphopoietic malignancies.
SO - Cancer Causes Control 2001 May;12(4):325-34
AD - Epidemiology Unit of National Cancer Research Institute, Genoa, Italy. email@example.com
OBJECTIVE: Tobacco use is the most prominent cause of respiratory cancers. Little is known, however, about the influence of smoking on hematolymphopoietic malignancies. To evaluate this relation, a population-based case-control study was carried out in 12 areas of Italy. METHODS: Detailed interviews on tobacco smoking habits were administered to 1450 non-Hodgkin's lymphoma (NHL), 365 Hodgkin's disease (HD), 270 multiple myeloma (MM), and 649 leukemia (LEU) patients occurring from 1990 to 1993, and 1779 population controls. RESULTS: We found a slightly increased risk for NHL in smokers (odds ratio 1.2, 95% confidence interval 1.0-1.4 for ever smokers), but a consistent positive association was shown only for follicular NHL. In this subtype, a significant excess risk was observed for ever versus never smokers, after adjustment for gender, age, geographic residence, education, and respondent (OR = 1.8, 95%, CI 1.3-2.7), with a positive exposure-response gradient for smoking duration (p < 0.01). The risk for follicular NHL was significantly elevated only among women, with ever smokers showing OR = 2.3 (CI 1.4-3.8), while for men we found OR = 1.3 (CI 0.69-2.3). No major differences were shown according to age. Female subjects also showed significant positive exposure-response trends for duration. CONCLUSION: Cigarette smoking could be a risk factor for follicular NHL among women. For HD, MM, or LEU, no clear association was observed.
UI - 11467752
AU - Kaplan AA
TI - Therapeutic apheresis for the renal complications of multiple myeloma and the dysglobulinemias.
SO - Ther Apher 2001 Jun;5(3):171-5
AD - Department of Medicine, University of Connecticut Health Center, Farmington 06030, USA. firstname.lastname@example.org
Disordered immunoglobulin synthesis can result in a variety of different types of renal pathology. Multiple myeloma is often associated with the overproduction of light chains which may result in toxicity to the renal tubules and acute renal failure. Patients with mixed cryoglobulinemia will have renal involvement which is most often in the form of a membranoproliferative glomerulonephritis. Renal involvement in macroglobulinemia is relatively uncommon, but IgM thrombi can be so voluminous as to occlude the glomerular capillary lumen. In each of these examples, therapeutic plasma exchange has been found to be a useful adjunct to the eventual chemotherapy required for the definitive treatment of these disorders.
UI - 11497339
AU - Thurmann PA; Sonnenburg C; Valentova K; Gregora E; Freischlager F;
TI - Lissner R Pharmacokinetics of viral antibodies after administration of intravenous immunoglobulin in patients with chronic lymphocytic leukaemia or multiple myeloma.
SO - Eur J Clin Pharmacol 2001 Jun;57(3):235-41
AD - University Witten/Herdecke, Hospital Wuppertal GmbH, Germany. email@example.com
OBJECTIVE: Intravenous immunoglobulin (IVIG) preparations are derived from human pooled plasma and should fulfil high standards of purity and viral safety. Introduction of additional purification steps, however, may result in modulation of the biological properties of immunoglobulins. Since cleavage of the Fab-fragment leads to a significant decrease in half-life, the latter provides information about the integrity of the immunoglobulin G (IgG) molecules. Therefore, a pharmacokinetic study of a novel preparation is required to determine safety and disposition in the target population. METHODS: Twenty-seven patients with chronic lymphocytic leukaemia (CLL) and 12 with multiple myeloma received intravenous infusions of IVIG containing antibodies against hepatitis B virus (anti-HBs; n= 15; 8960 IU), cytomegalovirus (anti-CMV; n = 9; 14,250 U) or varizella-zoster-virus (anti-VZV; n = 15; 6000 IU), respectively. Serum concentrations of viral antibodies were determined for 71 days during and after infusion. RESULTS: Maximum serum concentrations of anti-HBs, anti-CMV and anti-VZV were observed at about 4 h (median) after start of the infusion. Total body clearances came to 0.14 +/- 0.08 ml/min (anti-HBs), 0.10 +/- 0.02 ml/ min (anti-CMV) and 0.14 +/- 0.07 ml/min (anti-VZV). The terminal elimination half-lives were determined to be 25.34 +/- 8.34 days (anti-HBs), 24.66 7.28 days (anti-CMV) and 31.79 +/- 12.47 days (anti-VZV). Clinical chemistry parameters including C3- and C4-complement serum concentrations revealed no pathological changes, seroconversion for hepatitis B and C and HIV did not occur. CONCLUSIONS: The pharmacokinetic parameters of the IgG antibodies calculated after administration of the novel IVIG preparations to patients with CLL and multiple myeloma are in close agreement with data obtained from healthy volunteers and with values of native IgG, suggesting that the production process did not impair clinically relevant characteristics of the viral antibodies.
UI - 11498741
AU - Sirohi B; Powles R; Kulkarni S; Rudin C; Saso R; Lal R; Singhal S; Mehta
TI - J; Horton C; Treleaven J Comparison of new patients with Bence-Jones, IgG and IgA myeloma receiving sequential therapy: the need to regard these immunologic subtypes as separate disease entities with specific prognostic criteria.
SO - Bone Marrow Transplant 2001 Jul;28(1):29-37
AD - Leukaemia and Myeloma Units, Royal Marsden NHS Trust, Sutton, Surrey, UK.
Of the 61 newly diagnosed patients with Bence-Jones (BJ) myeloma sequential therapy (ST) comprising infusional chemotherapy (IC) followed by high-dose therapy and autotransplantation with interferon-alpha2b maintenance. The outcome was compared with 153 IgG and 39 IgA similarly treated myeloma patients. Response to IC and high-dose was comparable between the three subtypes but a significantly higher proportion of patients with BJ myeloma failed to receive high-dose compared to IgG (P = 0.003) and IgA (P = 0.04) myeloma. Median overall survival (OS) of patients with BJ myeloma (2.8 years) and event-free survival (EFS, 1.2 years) was significantly shorter than for patients with IgG myeloma (4.5 years, P = 0.03 and 2.1 years, P = 0.03, respectively). However, among those patients who achieved complete remission there was no difference in OS and EFS between IgG and BJ myeloma. In distinction to IgG myeloma where age and beta2M were significant, Cox analysis on presentation features identified performance status and urine total protein as having significant impact on OS. We conclude that achieving CR is an important treatment aim in patients with BJ myeloma, conferring a similar outlook on survival as in patients with the IgG subtype, and there is a need to consider different subtype-specific staging systems when evaluating the results of published or ongoing therapeutic trials.
UI - 11497393
AU - Egerer G; Hegenbart U; Salwender H; Haas R; Hahn U; Schmier JW; Ho AD;
TI - Goldschmidt H Outpatient treatment of multiple myeloma with a combination of vincristine, Adriamycin and dexamethasone.
SO - Support Care Cancer 2001 Jul;9(5):380-5
AD - Department of Hematology, University of Heidelberg, Germany. firstname.lastname@example.org
Patients with relapsed multiple myeloma (MM) have been shown to respond to a combination therapy consisting of vincristine, Adriamycin (doxorubicin) and high-dose dexamethasone (VAD). Because of the low hematological toxicity of the VAD regimen, this combination is frequently chosen for tumor reduction prior to high-dose therapy and blood stem cell transplantation. This study was designed to examine the efficacy and complications of outpatient VAD treatment. Over a period of 6 years, 103 outpatients with MM were treated with VAD chemotherapy administered by microprocessor-controlled infusion pumps via intravenous polyurethane catheters equipped with a safety valve. Response to treatment, treatment-associated complications and infections were documented and analyzed. In 85 of the 103 patients, tumor reduction by more than 25% was found. In 8 patients an occlusion occurred as a result of kinking of the central venous catheter in the subcutaneous segment. In two treatment cycles the infusions had to be stopped because of irreversible catheter occlusion. Twenty patients were hospitalized because of complications, which were infectious in 12 and noninfectious in 8. Severe infectious complications (> or =WHO grade III) occurred in 5.6% of the treatment cycles. Thus, continuous infusion of VAD over 96 h can be performed on an outpatient basis with a low complication rate.
UI - 11497396
AU - Takagi T; Sawamura M; Sezaki T; Kashimura M; Tsuchiya J; Hotta T; Ogawa
TI - N; Hirashima K Clinical benefits of lenograstim in patients with neutropenia due to chemotherapy for multiple myeloma (MM).
SO - Support Care Cancer 2001 Jul;9(5):397-9
AD - Chiba Cancer Center Hospital, Chiba City, Japan. email@example.com
The object of this study was to determine the efficacy and safety of glycosylated recombinant human granulocyte colony-stimulating factor (rHuG-CSF; lenograstim) after combination chemotherapy consisting of ranimustine, vindesine, melphalan and prednisolone (MCNU-VMP). One hundred thirty-nine consecutive patients with newly diagnosed multiple myeloma (MM) were allocated at random to a lenograstim group (n = 70) or a placebo group (n = 69). Patients were treated with two cycles of MCNU-VMP, and either lenograstim (2 microg/kg daily, s.c.) or placebo was administered from the day neutrophils decreased to less than 1.000/microl and was discontinued when neutrophils exceeded 5,000/microl. The median duration of neutropenia (neutrophils under 1,000/microl) was significantly shorter for the lenograstim group than the placebo group (2 days vs 9 days in the first cycle; 1 day vs 13 days in the second cycle). The incidence of febrile neutropenia in the first cycle was significantly lower in the lenograstim group than in the placebo group (9.2% vs 30.4%). No life-threatening infections were observed in either group. The two cycles of MCNU-VMP therapy were completed in 90.8% of the patients, and a higher average relative dose intensity (ARDI; 0.94) was achieved in the lenograstim group. The tumor response rate of the lenograstim group (57.8%) was higher than that of the placebo group (43.1%), but the difference was not statistically significant (chi2 = 2.634, df = 1, P = 0.105). Lenograstim was well tolerated, and no unexpected adverse events occurred. Lenograstim proved effective in controlling chemotherapy-induced neutropenia in MM patients under MCNU-VMP therapy.
UI - 11488852
AU - Kazmi MA; Ahsan G; Schey SA
TI - The effects of prior induction therapy with melphalan on subsequent peripheral blood progenitor cell transplantation for myeloma.
SO - Clin Lab Haematol 2001 Apr;23(2):125-9
AD - Department of Haematology, Guy's Hospital, St Thomas' Street, London, SE1 9RT, UK. Majid.Kazmi@btinternet.com
High dose chemoradiotherapy with autologous peripheral blood progenitor cell transplantation (PBPCT) may improve outcome in myeloma. Melphalan is an effective drug in the treatment of myeloma, but is potentially toxic to progenitor cells. We studied 8 patients receiving intermittent intravenous melphalan (25 mg/m2) as induction therapy before PBPCT to assess engraftment characteristics post-transplantation. Comparison was made with an age-matched control group of patients with non-Hodgkins lymphoma who had not received melphalan during induction therapy. There was correlation (P=0.037) between the dose of melphalan per kg body weight given, premobilization, and days to neutrophil engraftment, but no significant difference between the two groups in neutrophil recovery. The study group had delayed platelet recovery (P=0.01) and required more platelet support post-transplantation (P=0.05). 3-4 weekly melphalan (25 mg/m2) up to 6 courses was delivered to patients who went on to PBPCT without significantly influencing neutrophil recovery but with a negative impact on platelet recovery.
UI - 11504280
AU - Anderson KC
TI - Novel biologically based therapies for myeloma.
SO - Cancer J 2001 Jul-Aug;7 Suppl 1():S19-23
AD - Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Recent advances in our understanding of the molecular regulation of myeloma cells suggest novel strategies for treating multiple myeloma. Some myeloma cells express a 69 kD variant of Ku86, a heterodimer subunit that is essential for double-stranded DNA break repair. Presence of the variant impairs DNA repair; therefore normal Ku86 in myeloma cells confers resistance to therapy and may represent a therapeutic target. The upregulation of NF-kappaB-dependent interleukin-6 (IL-6) transcription and secretion that occurs following adhesion of myeloma cells to bone marrow stromal cells (BMSCs) may serve as a potential therapeutic target, as IL-6 is a growth and survival factor for myeloma cells. Accordingly, proteasome inhibitors inhibit activation of NF-kappaB and induce apoptosis of myeloma cells; they also inhibit the NF-kappaB-dependent up-regulation of IL-6 in BMSCs and related paracrine growth of adherent tumor cells. Therapeutic strategies may also target the mitogen-activated protein kinase (MAPK) pathway that is thought to mediate the IL-6-induced proliferation of myeloma cells. Vascular endothelial growth factor (VEGF) is also upregulated by adhesion of myeloma cells to BMSCs and may serve as a growth and/or survival factor for myeloma cells; preliminary studies suggest that VEGF receptor inhibitors may block proliferation of tumor cells. Thalidomide was recently used successfully to treat myeloma in patients whose disease was refractory to conventional treatment. An enhanced understanding of the mechanisms of action of thalidomide may result in the development of analogues with enhanced potency and fewer side effects. The potential mechanisms of action of thalidomide are reviewed, including antiangiogenic effects; direct effects of thalidomide on the growth and survival of myeloma cells and BMSCs; modulation of adhesive interactions; and regulation of secretion and bioactivity of cytokines. Immune-based strategies for treating multiple myeloma are also reviewed. Therapeutic obstacles include excessive toxicity after allografting, contaminating tumor cells in autografts, and the persistence of minimal residual disease (MRD) after high-dose therapy followed by allogenic or autologous stem cell transplantation. Allografting can be performed safely in myeloma, donor lymphocyte infusions (DLI) may effectively treat relapsed myeloma post allografting; and use of CD4+ T cell-enriched DLI may reduce the risk of graft-versus-host disease. Treatment with autografting is frequently compromised by MRD in the autograft and in the patient post myeloablative therapy. Adenoviral purging prior to autotransplantation and in vivo and ex vivo stimulation of autoimmune cells are discussed as potential approaches to address these problems.
UI - 11505750
AU - Cielinska S; Urbaniak-Kujda D; Gabrys K; Kuliczkowski K
TI - [Coincidence of multiple myeloma and renal clear cell adenocarcinoma]
SO - Pol Arch Med Wewn 2001 Feb;105(2):153-6
AD - Katedra i Klinika Hematologii i Chorob Rozrostowych AM we Wroclawiu.
There are only casuistic reports about the coincidence of renal carcinoma and lymphoproliferative diseases. We report a case of 59-year old patient who simultaneously developed renal clear cell carcinoma and IgG kappa multiple myeloma. After nephrectomy the progression of multiple myeloma was observed. The renal failure occurred and, as a consequence, the introduction of full doses of chemotherapy for multiple myeloma was unable.
UI - 11512598
AU - Diamond T; Levy S; Smith A; Day P; Manoharan A
TI - Non-invasive markers of bone turnover and plasma cytokines differ in osteoporotic patients with multiple myeloma and monoclonal gammopathies of undetermined significance.
SO - Intern Med J 2001 Jul;31(5):272-8
AD - Department of Endocrinology, St George Hospital, University of New South Wales, Sydney, Australia. firstname.lastname@example.org
AIMS: To determine whether various markers of bone turnover and/or plasma cytokines differ in patients with multiple myeloma (MM) compared with patients with monoclonal gammopathies of undetermined significance (MGUS). METHODS: We studied 22 MM patients and 18 MGUS patients presenting over an 18-month period and compared their data with those from 20 age- and sex-matched patients presenting with primary osteoporosis. According to the Salmon and Durie classification, there were eight patients with stage I, nine with stage II and five with stage III disease. All patients had densitometric evidence of osteoporosis and were classified according to bone marrow evidence of plasma cell dyscrasia. Measured variables included markers of bone formation and bone resorption, and plasma cytokines. RESULTS: Patients with MM and MGUS did not differ with respect to their mean age, male : female sex ratio, height, weight, serum calcium, 25-hydroxyvitamin D and parathyroid hormone concentrations. Patients with MM had significantly lower concentrations of haemoglobin (109 vs 135 g/L) and serum transforming growth factor (TGF)-beta (261 vs 348 pg/mL) than patients with MGUS, and higher concentrations of serum paraproteins (31.1 vs 7.4 g/L), beta2-microglobulin (3.5 vs 2.2 g/L), % plasma cell numbers (35.3 vs 2.1%) and urinary deoxypyridinoline excretion rates (u-DPYD; 7.7 vs 5.9 nmol/mmol creatinine; P < 0.05 for all comparisons). In multivariate analysis, the serum paraprotein (beta coefficient = -0.067; 95% confidence intervals (CI), -0.019 to -0.005; P = 0.0012), u-DPYD excretion rates (beta coefficient = -0.012; 95% CI, -0.113 to -0.02; P= 0.0058) and serum TGF-beta concentrations (beta coefficient = -0.002; 95% CI, -0.0002 to -0.02; P= 0.02) were the most important variables differentiating between MM and MGUS, after excluding lytic bone lesions, % plasma cell numbers and haemoglobin concentrations. CONCLUSIONS: The well-established criteria for diagnosing MM include the presence of lytic bone lesions, plasmacytosis, haemoglobin and paraprotein concentrations. The u-DPYD excretion rate, a sensitive non-invasive marker of bone resorption, may help in differentiating between MM and MGUS, as well as serving as a marker of underlying bone disease activity in these patients.
UI - 11524732
AU - Bezieau S; Devilder MC; Avet-Loiseau H; Mellerin MP; Puthier D; Pennarun
TI - E; Rapp MJ; Harousseau JL; Moisan JP; Bataille R High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis.
SO - Hum Mutat 2001 Sep;18(3):212-24
AD - Laboratoire de Genetique Moleculaire, Institut de Biologie, Nantes, France.
Using allele-specific amplification method (ARMS), a highly sensitive one-stage allele-specific PCR, we have evaluated the incidence of NRAS and KRAS2 activating mutations (codons 12, 13, and 61) in 62 patients with either monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM), primary plasma-cell leukemia (P-PCL), and also in human myeloma cell lines (HMCL). NRAS and/or KRAS2 mutations were found in 54.5% of MM at diagnosis (but in 81% at the time of relapse), in 50% of P-PCL, and in 50% of 16 HMCL. In contrast, the occurrence of such mutations was very low in MGUS and indolent MM (12.50%). Of note, KRAS2 mutations were always more frequent than NRAS. The validity of the technique was assessed by direct sequencing of cell lines and of some patients. Multiple mutations found in two patients were confirmed by subcloning exon PCR amplification products, testing clones with our method, and sequencing them. Thus, these early mutations could play a major role in the oncogenesis of MM and P-PCL. Copyright 2001 Wiley-Liss, Inc.
UI - 11571504
AU - Mohty M; Fegueux N; Exbrayat C; Lu ZY; Legouffe E; Quittet P;
TI - Lopez-Martinez E; Latry P; Avinens O; Hertog C; Klein B; Eliaou JF; Rossi JF Reduced intensity conditioning: enhanced graft-versus-tumor effect following dose-reduced conditioning and allogeneic transplantation for refractory lymphoid malignancies after high-dose therapy.
SO - Bone Marrow Transplant 2001 Aug;28(4):335-9
AD - Hematologie et Oncologie Medicale, CHU de Montpellier, Montpellier, France.
Non-myeloablative regimens have been proven to allow engraftment following allogeneic stem cells transplantation (allo-SCT) with minimal procedure-related toxicity. Conventional allo-SCT may produce remissions in patients with relapsed and refractory lymphoid malignancies (LM) but these good results may be achieved at the cost of high treatment-related morbidity and mortality. Application of allo-SCT using less intensive regimens may temper the frequency of these complications, allowing a potent graft-versus-tumor effect (GVT). We present our data on 11 patients with LM receiving allo-SCT with a reduced regimen. Ten patients had received previous high-dose therapy, and were at high risk for toxicity, thus precluding the use of allo-SCT. A fludarabine and low-dose busulfan combination facilitated engraftment while exerting GVT. Hematological recovery was quick, and full donor T cell chimerism preceded acute GVHD. GVHD and infections were the major problems. Spontaneous acute GVHD occurred in eight patients (72%). Five patients (45%) achieved complete remission, and the GVT effect was closely associated with GVHD. These results support the concept that GVT is effective against LM in patients who have been heavily pretreated. Further studies are needed to investigate strategies to generate more specific alloreactive effects providing optimal GVT and an acceptable risk of GVHD and infections.
UI - 11572076
AU - Hegemann B; Helmbold P; Dickert C; Marsch WC
TI - [Recurrent chancriform mucous membrane ulcer in plasmacytoma with secondary IgA deficiency. Pyoderma chancriforme of the tongue]
SO - Hautarzt 2001 Sep;52(9):820-3
AD - Universitatsklinik und Poliklinik fur Dermatologie und Venerologie der Martin-Luther-Universitat Halle-Wittenberg, Ernst-Kromayer-Strasse 5-6, 06097 Halle/Saale. email@example.com
A 66 year old patient presented with a nine month history of recurrent oral ulcerations involving the tongue. We diagnosed chancriform pyoderma and a previously not identified multiple myeloma with secondary immunoglobulin deficiency. Clinically and histologically we excluded a necrotizing ulcerative stomatitis as found in individuals with cellular immunodeficiency as in late-stage HIV-infection. On culture only Neisseria catarrhalis was found. Chancriform pyoderma is often associated with local bacterial infections, especially Staphylococcus aureus. The most common sites are the genitalia and periorbital region; involvement of the oral mucosa is uncommon. To the best of our knowledge, this is the fourth reported case with tongue lesions. The multiple myeloma-associated immunoglobulin deficiency might have facilitated the oral manifestations of chancriform pyoderma.
UI - 11564069
AU - Badros A; Barlogie B; Siegel E; Roberts J; Langmaid C; Zangari M;
TI - Desikan R; Shaver MJ; Fassas A; McConnell S; Muwalla F; Barri Y; Anaissie E; Munshi N; Tricot G Results of autologous stem cell transplant in multiple myeloma patients with renal failure.
SO - Br J Haematol 2001 Sep;114(4):822-9
AD - Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA. firstname.lastname@example.org
Data are presented on 81 multiple myeloma (MM) patients with renal failure (creatinine > 176.8 micromol/l) at the time of autologous stem cell transplantation (auto-SCT), including 38 patients on dialysis. The median age was 53 years (range: 29-69) and 26% had received more than 12 months of prior chemotherapy. CD34+ cells were mobilized with granulocyte colony-stimulating factor (G-CSF) alone (n = 51) or chemotherapy plus G-CSF (n = 27), yielding medians of 10 and 16 x 106 CD34+ cells/kg respectively (P = 0.003). Sixty patients (27 on dialysis) received melphalan 200 mg/m2 (MEL-200). Because of excessive toxicity, the subsequent 21 patients (11 on dialysis) received MEL 140 mg/m2 (MEL-140). Thirty-one patients (38%) completed tandem auto-SCT, including 11 on dialysis. Treatment-related mortality (TRM) was 6% and 13% after the first and second auto-SCT. Median times to absolute neutrophil count (ANC) > 0.5 x 109/l and to platelets > 50 x 109/l were 11 and 41 d respectively. Non-haematological toxicities included mucositis, pneumonitis, dysrhythmias and encephalopathy. At a median follow up of 31 months, 30 patients have died. Complete remission (CR) was achieved in 21 patients (26%) after first SCT and 31 patients (38%) after tandem SCT. Two patients discontinued dialysis after SCT. Median durations of complete remission (CR) and overall survival (OS) have not been reached; probabilities of event-free survival (EFS) and OS at 3 years were 48% and 55% respectively. Dialysis dependence and MEL dose did not affect EFS or OS. Sensitive disease prior to SCT, normal albumin level and younger age were independent prognostic factors for better OS. In conclusion, renal failure had no impact on the quality of stem cell collections and did not affect engraftment. MEL-140 had an acceptable toxicity and appeared equally effective as MEL-200. In the setting of renal failure, the role of auto-SCT early in the disease course and benefits of tandem SCT require further evaluation.
UI - 11568006
AU - Chen Q; Gong B; Mahmoud-Ahmed AS; Zhou A; Hsi ED; Hussein M; Almasan A
TI - Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma.
SO - Blood 2001 Oct 1;98(7):2183-92
AD - Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
It has been reported that interferons (IFNs) may have antitumor activity in multiple myeloma (MM). The mechanism for their effect on MM, however, remains elusive. This study shows that IFN-alpha and -beta, but not -gamma, induce apoptosis characterized by Annexin V positivity, nuclear fragmentation and condensation, and loss of clonogenicity in 3 MM cell lines (U266, RPMI-8266, and NCI-H929), and in plasma cells from 10 patients with MM. Apo2 ligand (Apo2L, also TRAIL) induction was one of the earliest events following IFN administration in U266 cells. Treatment of these cells with TRAIL, but not with Fas agonistic antibodies, induces apoptosis. Cell death induced by IFNs and Apo2L in U266 cells was partially blocked by a dominant-negative Apo2L receptor, DR5, demonstrating the functional significance of Apo2L induction. This study shows that IFNs activate caspases and the mitochondrial-dependent apoptotic pathway, possibly mediated by Apo2L production. Thus, IFN-alpha and -beta induce cytochrome c release from mitochondria starting at 12 hours, with an amplified release seen at 48 hours. Moreover, Bid cleavage precedes the initial cytochrome c release, whereas the late, amplified cytochrome c release coincides with changes in levels of Bcl-2, Bcl-X(L), and reduction of mitochondrial membrane potential. These results link the Apo2L induction and modulation of Bcl-2 family proteins to mitochondrial dysfunction. Furthermore, IFNs and Apo2L induce cell death of CD38(+)/CD45(-/dim) plasma cells, without significant effect on nonplasma blood cells, in a caspase and Bcl-2 cleavage-dependent manner. These results warrant further clinical studies with IFNs and Apo2L in MM.
UI - 11568016
AU - Seidel C; Hjertner O; Abildgaard N; Heickendorff L; Hjorth M; Westin J;
TI - Nielsen JL; Hjorth-Hansen H; Waage A; Sundan A; Borset M; Nordic Myeloma Study Group Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease.
SO - Blood 2001 Oct 1;98(7):2269-71
AD - Institute of Cancer Research