Veno-occlusive disease of the liver after high-dose cytoreductive therapy with busulfan and melphalan for autologous blood stem cell transplantation in multiple myeloma patients.

Veno-occlusive disease of the liver (VOD) is a potentially severe complication of high-dose cytoreductive therapy (HDT) used for stem cell transplantation (SCT). This complication is uncommon after HDT for autologous SCT (ASCT) in patients with multiple myeloma (MM). The Spanish Myeloma Group/PETHEMA conducted a study (MM2000) for patients with newly diagnosed MM consisting of induction with alternating VBMCP/VBAD chemotherapy followed by intensification with busulfan/melphalan (Bu/MEL) with a second high-dose therapy procedure in patients not achieving at least near-complete remission with the first procedure.

Complications of multiple myeloma.

Multiple myeloma, also known as myeloma or plasma cell myeloma, is a progressive hematologic disease. Complications of multiple myeloma include renal insufficiency, hematologic complications (anemia, bone marrow failure, bleeding disorders), infections, bone complications (pathologic fractures, spinal cord compression, hyercalcemia), and neurologic complications (spinal cord and nerve root compression, intracranial plasmacytomas, leptomeningeal involvement, among others). This article reviews these various complications connected to multiple myeloma, examining their various causes and possible treatment.

Phase II PETHEMA trial of alternating bortezomib and dexamethasone as induction regimen before autologous stem-cell transplantation in younger patients with multiple myeloma: efficacy and clinical implications of tumor response kinetics.

Purpose: This is the first study in which bortezomib and dexamethasone were administered on an alternating basis as up-front therapy in multiple myeloma (MM). We investigated the efficacy and kinetics of response to each drug and safety.

Patients And Methods: Patients with newly diagnosed MM who were less than 66 years old were treated with bortezomib at 1.

Monoclonal gammopathy of undetermined significance: predictors of malignant transformation and recognition of an evolving type characterized by a progressive increase in M protein size.

Objective: To investigate the predictors of monoclonal gammopathy of undetermined significance (MGUS) by considering not only the initial features but also the pattern of evolution of the M protein during the first years after diagnosis.

Patients And Methods: This study consisted of 359 patients diagnosed as having MGUS at a single institution. Patients who showed a definite and progressive increase in their M protein size according to serum electrophoresis during the first 3 years of follow-up were considered to have evolving MGUS, whereas all others were considered to have nonevolving MGUS.

Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis.

Fluorescence in situ hybridization (FISH) has become a powerful technique for prognostic assessment in multiple myeloma (MM). However, the existence of associations between cytogenetic abnormalities compels us to re-assess the value of each abnormality. A total of 260 patients with MM at the time of diagnosis, enrolled in the GEM-2000 Spanish transplant protocol, have been analyzed by FISH in order to ascertain the independent influence on myeloma prognosis of IGH translocations, as well as RB and P53 deletions.

Long-term results of thalidomide in refractory and relapsed multiple myeloma with emphasis on response duration.

Objective: Thalidomide administered as a single agent produces a response rate of about 40% in patients with refractory or relapsed multiple myeloma (MM). The aim of our study was to determine the quality and duration of such responses.

Patients And Methods: Forty-two consecutive patients with refractory (20) or relapsed (22) MM were given thalidomide as a single agent at our institution.

Smoldering multiple myeloma and monoclonal gammopathy of undetermined significance.

Smoldering multiple myeloma (SMM) consists of the presence of a serum M protein of 30 g/L or more and/or 10% or more bone marrow plasma cells (BMPCs), with no clinical manifestations or symptoms of myeloma. It accounts for approximately 10% of all myelomas, and the median time to progression to a symptomatic multiple myeloma ranges from 2 to 3 years. The main factors for progression are the plasma cell mass (M-protein size and percent of BMPCs), the spinal MRI pattern, the plasma cell proliferative index, and the variant of SMM ("evolving" vs "nonevolving").

Bortezomib: a valuable new antineoplastic strategy in multiple myeloma.

Although the treatment of multiple myeloma has improved over the past decade, the disease remains incurable. Bortezomib, a first-in-class selective proteasome inhibitor, was approved in the United States in 2003 and the European Union in 2004 for the treatment of relapsed and refractory multiple myeloma in patients who have received at least 2 prior therapies and demonstrated disease progression on the last therapy. In vitro, bortezomib induces apoptosis of multiple myeloma cells and inhibits cell adhesion within the bone marrow microenvironment.

Comparative genomic hybridisation identifies two variants of smoldering multiple myeloma.

Two variants of smoldering multiple myeloma (SMM) have been recognised: (i) an evolving type, characterised by a progressive increase in the M-protein size and short time to progression to overt multiple myeloma (MM) and (ii) a non-evolving type, with a long-lasting, stable M-protein and longer time to progression. Comparative genomic hybridisation (CGH) analyses in both subtypes of SMM (seven evolving and eight non-evolving SMM) were performed. Evolving SMM showed cytogenetic changes consistent with those found in de novo symptomatic MM (1q gains, chromosome 13 deletions) while the non-evolving variant showed no 1q gains and deletions were uncommon.

High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA.

The aim of the present randomized trial was to compare high-dose therapy (HDT) with continued conventional chemotherapy in patients with multiple myeloma (MM) who responded to the initial treatment. From May 1994 to October 1999, 216 patients (122 men/94 women; stage II or III; Eastern Cooperative Oncology Group [ECOG] score less than 3) entered the study. Initial chemotherapy consisted of 4 cycles of alternating vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, Adriamycin, dexamethasone (VBMCP/VBAD).

Renal, hematologic and infectious complications in multiple myeloma.

Renal failure is a common complication in patients with multiple myeloma. It is generally due to tubular light-chain damage, and it is reversible in about 50% of patients. The reversibility rate depends on the degree of light-chain nephropathy.

Bortezomib-induced severe hepatitis in multiple myeloma: a case report.

Bortezomib is a novel proteasome inhibitor with significant antimyeloma activity. Its toxicity is manageable, and the most frequent adverse effects mainly consist of gastrointestinal symptoms, peripheral neuropathy, neuropatic pain, and thrombocytopenia. Severe liver toxicity has not been previously recognized.

Aminoglycoside-associated severe renal failure in patients with multiple myeloma treated with thalidomide.

Thalidomide has been proved to play an important role in rescue treatment of patients with refractory/relapsed multiple myeloma (MM). However, thalidomide therapy is associated with numerous side effects, mainly somnolence, constipation, fatigue or peripheral neuropathy. We report three patients diagnosed with MM and treated with thalidomide as salvage therapy who developed severe renal failure when they received aminoglycoside antibiotics.

Extramedullary multiple myeloma escapes the effect of thalidomide.

Background And Objectives: Thalidomide is an antiangiogenic drug that produces a response rate ranging from 32 to 64% in patients with refractory/relapsed multiple myeloma (MM). However, the efficacy of thalidomide in patients with soft-tissue plasmacytomas is controversial. The aim of this study was to assess the response rate to thalidomide in patients with advanced MM and to correlate the response rate with the presence of extramedullary involvement.

Response to thalidomide in multiple myeloma: impact of angiogenic factors.

Thalidomide has antiangiogenic and immunomodulatory effects, mediated by several cytokines such as vascular endothelial growth factor (VEGF), fibroblastic growth factor (FGF-2), hepatocyte growth factor (HGF), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Although extramedullary plasmacytomas (EMP) have a high vascularization, the response of these patients to thalidomide is controversial. Thirty-eight patients with refractory/relapsed MM were treated with thalidomide.

High-dose therapy/autologous stem cell transplantation in patients with chemosensitive multiple myeloma: predictors of complete remission.

High-dose therapy (HDT) followed by autologous stem cell support is widely used as intensification treatment in patients with multiple myeloma (MM) responsive to the initial chemotherapy. However, there is growing evidence that only the subset of patients who achieve complete remission (CR) actually benefit from this approach. The aim of this study was to identify pretransplant predictors of CR in responding myeloma patients intensified with HDT.

Smoldering multiple myeloma: natural history and recognition of an evolving type.

Patients with smoldering multiple myeloma (SMM) meet the diagnostic criteria of multiple myeloma (MM) but are asymptomatic. Between January 1978 and July 2001, 53 patients (median age 63 years) were diagnosed with SMM. The median serum M-protein and proportion of bone marrow plasma cells were 36 g/l and 27% respectively.

Appropriateness of applying the response criteria for multiple myeloma to Waldenstrom's macroglobulinemia?

Since the presence of an M-component is an essential disease feature in both multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM), the decrease in the M-protein size applied for response in MM is also a crucial criteria for assessing response in WM. However, WM frequently displays lymphoma-like features that should be included in the response criteria.

Malignant transformation in IgM monoclonal gammopathy of undetermined significance.

Monoclonal gammopathy of undetermined significance (MGUS) is a frequent disorder characterized by the presence of a small serum M-protein in individuals with no evidence of multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM), or primary amyloidosis (AL). Although one fourth of these individuals will develop a malignant disease, there are no well-established predictors of outcome, particularly in the IgM type MGUS. Among 434 patients diagnosed with MGUS from 1970 to 2001 with a minimum follow-up of 1 year, 52 (27 men and 25 women; median age, 67 years) of IgM type were identified.

Limitations of Gallium-67 SPECT in histological transformation of chronic lymphocytic leukaemia: an analysis of 13 patients with clinically suspected Richter's syndrome.

Gallium-67 single photon emission computerized tomography (Ga-67 SPECT) was performed in 13 chronic lymphocytic leukaemia (CLL) patients suspected of evolution into diffuse large B-cell lymphoma (DLCL) or Richter's syndrome (RS). Six positive and nine negative Ga-67 SPECTs were observed. Ten patients were biopsied (five in each group).

Primary systemic amyloidosis presenting as a colonic stricture: successful treatment with left hemicolectomy followed by autologous hematopoietic stem-cell transplantation: report of a case.

Intestinal tract involvement by primary systemic amyloidosis is frequent but usually asymptomatic. Ischemic colitis caused by amyloid infiltration of wall blood vessels can occasionally be observed. We report a 62-year-old female with primary systemic amyloidosis who presented with intestinal obstruction caused by ischemic stricture of the sigmoid colon, secondary to submucosal amyloid deposition.

Idiopathic myelofibrosis associated with primary biliary cirrhosis.

A patient with primary biliary cirrhosis (PBC) who developed idiopathic myelofibrosis (IM) is reported. The initial diagnosis of PBC was established by liver biopsy, performed after a 2-month history of constitutional symptoms associated with abnormalities of the serum liver enzymes, with typical serum immunological markers being found. Although a favorable response of PBC to prednisone was observed, one and a half year later the patient developed anemia with anisocytosis and poikilocytosis, tear-drop cells, and leukoerythroblastic picture, and IM was diagnosed by bone marrow biopsy.