Multiple myeloma-associated amyloidosis is an independent high-risk prognostic factor.

Several prognostic factors have been recognized in patients with multiple myeloma (MM). Among the most important are: the serum levels of beta2-microglobulin, albumin, and LDH; the labeling index; and an abnormal karyotype. Patients with amyloidosis (AL) have poor prognosis; however, little is known concerning the prognostic significance of AL associated to MM. In 201 consecutive patients with de novo MM, we performed a fat-pad biopsy needle aspiration (FPBNA) that was stained with Congo red. Sixty eight (34%) patients had AL and a poorer prognosis disease: lower performance status, presence of B symptoms, higher LDH and calcium values, and worse response to chemotherapy. Cox regression model for overall survival detected three variables having independent prognostic significance: the presence of AL (RR = 3.4, P < 0.004), serum albumin levels <3.5 g/dl (RR 3.2, p < 0.005), and patients not achieving complete remission or very good partial remission (RR 2.9, p < 0.02). In 28% of patients with de novo MM, FPBNA was useful to detect incidental amyloidosis. During follow-up, 69% of these patients had symptoms of AL. Excluding 16 patients with obvious symptoms of AL at diagnosis, overall survival was worse in patients who developed later symptoms of AL. MM-associated AL represents a poorer prognosis disease even in the absence of symptoms at diagnosis, and this specific association may be considered as an independent high-risk prognostic factor. The routine study of periumbilical fat-pad tissue should be mandatory in all patients with MM.

Autologous peripheral blood stem cell transplantation in multiple myeloma using oral versus I.V. melphalan.

Autologous peripheral blood stem cell transplantation is the therapy of choice for the treatment of multiple myeloma (MM) patients younger than 70 years old. Between August 1993 and November 2004, 54 patients with MM were autografted after conditioning with high-dose oral melphalan 140 mg/m(2) in combination with etoposide and carmustine (28 patients) or with high-dose melphalan 200 mg/m(2) I.V. (26 patients). The oral and IV melphalan groups were comparable. There were no significant differences in disease-free survival (DFS) and overall survival (OS) between the groups; however, in patients transplanted in remission, OS and DFS were better in the I.V. melphalan group. Four good-prognostic factors were identified: interval between diagnosis and transplant <18 months, number of prior chemotherapy lines < or =2, remission status (complete or partial), and the use of I.V. melphalan. In conclusion, I.V. melphalan is the therapy of choice for conditioning patients with MM who are in remission.

[CD200 protein, bad prognostic in patients with multiple myeloma]. / Proteína CD200 de mal pronóstico en pacientes con mieloma múltiple.

BACKGROUND: Multiple myeloma (MM) is a monoclonal gammopathy characterized by abnormal proliferation of malignant plasma cells. The median overall survival rate has changed from 2-3 to 5-6 or more years with the introduction of novel agents. Recently CD200 protein has been described as an immunosuppressive protein that confers a poor prognostic factor in several neoplastic diseases, including MM. The purpose of our study was to determine CD200 protein in plasma cells of newly diagnosed patients with MM and in CD3+ lymphocytes of healthy donors. METHODS: 35 newly diagnosed MM patients and 25 healthy donors were studied. For flow cytometry tests, a FacsCalibur device and CellQuestPro software were used. Monoclonal antibodies for CD38 (PeCyC5), CD138 (APC), and CD200 (PE) were used. The statistical analysis was performed with SPSS 19v. Mann-Whitney U test, Kaplan-Meier survival curves with Log-Rank tests were done when indicated. RESULTS: The frequencies of anemia, hypercalcemia, increased in LDH, serum creatinine and b2-microglobulin were 68%, 34%, 20%, 22% and 45% respectively. The treatment consisted in MPT 20 (57%), Thal-Dex 8 (23%), and VAD 7 (20%). Five patients (14%) achieved complete response, 17 (49%) partial response, and 13 (37%) minor response or failure to treatment. CONCLUSION: CD200 is a poor prognostic factor for overall survival in multiple myeloma patients. Bone marrow CD3 lymphocytes from MM patients express CD200 protein in higher proportion than healthy donors.

Introducción: el mieloma múltiple (MM) es una gammopatía monoclonal caracterizada por la proliferación anormal de células plasmáticas malignas. La proteína CD200 se ha descrito como una proteína con funciones inmunosupresoras y que es un factor de mal pronóstico en algunas enfermedades malignas, incluyendo al MM. El objetivo de este artículo es determinar la cantidad de proteína CD200 en células plasmáticas de pacientes con MM de reciente diagnóstico y en linfocitos CD3+ de donadores sanos. Métodos: se estudiaron 35 pacientes con diagnóstico reciente de MM y 25 individuos sanos. Se usaron los anticuerpos monoclonales para CD38 (PeCyC5), CD138 (APC), y CD200 (PE). El análisis estadístico fue realizado con el programa SPSS 19v. Se utilizaron las pruebas estadísticas U de Mann Whitney, curvas de supervivencia de Kaplan y Meier y la prueba de log-rank. Resultados: las frecuencias de anemia, hipercalcemia, elevación de DHL, creatinina sérica y beta-2 microglobulina fueron de 68%, 34%, 20%, 22% y 45% respectivamente. El tratamiento administrado fue MPT 20, Tal-Dex 8, y VAD 7. Cinco pacientes lograron respuesta completa, 17 respuesta parcial, y 13 respuesta menor o falla al tratamiento. Conclusiones: el CD200 es un factor de mal pronóstico para supervivencia global en pacientes con mieloma múltiple. Los linfocitos CD3+ de medula ósea de pacientes con MM expresan en mayor proporción CD200 en comparación con sujetos sanos.

IFN-alpha as induction and maintenance treatment of patients newly diagnosed with Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia is a rare malignant disorder of B lymphocytes. There are no studies on the use of interferon-alpha (IFN-alpha) as frontline therapy in this disease. Between April 1991 and September 2000, we treated 21 newly diagnosed patients using 8 mg/m(2) chlorambucil and 40 mg/m(2) prednisone p.o. daily for 10 days and 3 megaU/m(2) IFN-alpha three times a week. Patients who responded after induction continued receiving IFN until relapse or death. We found a high frequency of peripheral neuropathy (43%) and grade 3 diffuse marrow fibrosis (43%). Objective response was achieved in 12 (57%) patients, including 4 (19%) complete responders. Median time from treatment to response was 8 months (range 3-18). Median progression-free survival was 70 months (95% CI 47-93), and overall survival was 91 months (95% CI 50-132). Patients who achieved objective response lived longer (91 vs. 33 months, p < 0.03), as did patients who had lactic dehydrogenase (LDH) < 180 U/L (89 vs. 54 months, p < 0.01). Grade 3 hematologic toxicity was observed during induction in 5 patients. IFN-alpha is an effective agent for the induction and maintenance treatment of Waldenström's macroglobulinemia patients. LDH > 180 U/L and failure to respond are adverse prognostic factors.

Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia.

Primary plasma cell leukemia (PPCL) is a rare form of disease accounting for 1-2 percent of myelomas. Between September 1990 and November 2000, among 540 patients with myeloma studied, 24 fulfilled the criteria of PPCL (4.4 percent). We found high frequencies of female patients (62 percent), Bence Jones proteinuria (79 percent), anemia (88 percent), bleeding (54 percent), confusional syndrome (42 percent), weight loss (71 percent), hepatomegaly (25 percent), splenomegaly (21 percent), leukocytosis (62 percent), and thrombocytopenia (71 percent). High serum levels of creatinine, calcium, lactate dehydrogenase (LDH), and beta(2)-microglobulin were detected in 50 percent, 37 percent, 58 percent, and 71 percent, respectively. Four patients were treated with vincristine, melphalan, cyclophosphamide, prednisone, and adriamycin (VMCPA), 12 with vincristine, adriamycin, and dexamethasone (VAD), and 8 with M-80 (oral melphalan 80 mg/m(2) plus dexamethasone 40 mg/m(2)). There was a trend toward lower values of Karnofsky score (P=0.07) and higher values of LDH (P=0.2) in the VAD group. Other clinical characteristics were comparable among the three groups. Complete plus partial responses were achieved in one and six patients treated with VMCPA and M-80, respectively. All patients treated with VAD failed to respond to treatment. Patients receiving the M-80 regimen experienced higher platelet toxicity (P=0.05), vomiting (P<0.0003), and mucositis. Also, the need for red blood cell transfusions was higher in the M-80 group. Median overall survival was 60 days. Overall survival was better in patients achieving complete or partial response. In conclusion, our study illustrates that intermediate doses of melphalan plus dexamethasone are an effective chemotherapy regimen for this aggressive disease. Response to treatment is the only prognostic factor for survival in these patients.