Multiple myeloma in young patients: clinical presentation and treatment approach

Multiple myeloma (MM) in patients younger than 40 or 30 years accounts for only 2% and 0.3% of all myelomas, respectively. The presenting clinical and laboratory features are similar to those observed in patients of all ages who have myeloma, except a higher proportion of young patients have only light-chain myeloma. Some very young patients, particularly those younger than 30 years, have multiple skeletal lesions with extramedullary spread and a small M-component with few bone marrow plasma cells. In young patients with MM, particularly in those with good prognostic features (that is, normal renal function or low beta2-microglobulin level) and also in those younger than 30 years, the survival is longer than that in series of patients of all ages with MM. Young patients with MM might benefit from early high-dose therapy followed by autologous or allogeneic stem cell rescue. The current status of autologous and allogeneic transplantation in MM is reviewed.     

Pain mapping during minilaparoscopy in infertile patients without pathology

Multiple myeloma (MM) typically afflicts elderly patients with a median age of 65 years. However, while recently shown to provide superior outcome to standard treatment, high-dose therapy (HDT) has usually been limited to patients up to 65 years. Among 550 patients with MM and a minimum follow-up of 18 months, 49 aged >/=65 years were identified (median age, 67; range, 65 to 76 years). Their outcome was compared with 49 younger pair mates (median, 52; range, 37 to 64 years) selected among the remaining 501 younger patients (<65 years) matched for five previously recognized critical prognostic factors (cytogenetics, beta2-microglobulin, C-reactive protein, albumin, creatinine). Nearly one half had been treated for more than 1 year with standard therapy and about one third had refractory MM. All patients received high-dose melphalan-based therapy; 76% of the younger and 65% of the older group completed a second transplant (P =.3). Sufficient peripheral blood stem cells to support two HDT cycles (CD34 > 5 x 10(6)/kg) were available in 83% of younger and 73% of older patients (P =.2). After HDT, hematopoietic recovery to critical levels of granulocytes (>500/microL) and of platelets (>50,000/microL) proceeded at comparable rates among younger and older subjects with both first and second HDT. The frequency of extramedullary toxicities was comparable. Treatment-related mortality with the first HDT cycle was 2% in younger and 8% among older subjects, whereas no mortality was encountered with the second transplant procedure. Comparing younger/older subjects, median durations of event-free and overall survival were 2.8/1.5 years (P =.2) and 4.8/3.3 years (P =.4). Multivariate analysis showed pretransplant cytogenetics and beta2-microglobulin levels as critical prognostic features for both event-free and overall survival, whereas age was insignificant for both endpoints (P =.2/.8). Thus, age is not a biologically adverse parameter for patients with MM receiving high-dose melphalan-based therapy with peripheral blood stem cell support and, hence, should not constitute an exclusion criterion for participation in what appears to be superior therapy for symptomatic MM.     

Long-term survival (10 years or more) in 30 patients with primary amyloidosis

The median survival in primary systemic (AL) amyloidosis is less than 18 months. No published series of patients with AL amyloidosis have reported survival of more than 10 years. The records of all Mayo Clinic patients with a diagnosis of AL amyloidosis between January 1, 1966 and March 1, 1987 were reviewed. Patients with secondary amyloidosis, familial amyloidosis, senile systemic amyloidosis, and localized amyloidosis were excluded. During the 21 years of the study, 841 patients with AL amyloidosis were seen. Of these, 29 were excluded because the diagnosis was made at autopsy, and 2 others were excluded because no follow-up data were available. Actuarial survival for the 810 patients was 51% at 1 year, 16% at 5 years, and 4.7% at 10 years. Thirty patients survived for 10 years or more after the histologic diagnosis of AL amyloidosis; all received alkylating-agent therapy. In 14 patients, the monoclonal protein disappeared from the serum or urine. Of 10 patients with nephrotic syndrome, 4 had an objective response. Congestive heart failure, older age, creatinine value of 2 mg/dL or more, bone marrow plasma cell value of 20% or more, platelet count of 500 x 10(9)/L or less, and the presence of peripheral neuropathy were underrepresented in the 10-year survivors and are unfavorable prognostic features. Five percent of patients with AL amyloidosis survived for 10 years or more.     

Cortisol induces apoptosis in activated B cells, not in other lymphoid cells of the common carp, Cyprinus carpio L.

Two-hundred and 31 patients with a newly diagnosed multiple myeloma first seen and admitted to 17 hospitals located in the North-East of Italy between 1987 and 1992, were registered for a prospective study on the course of the disease. Median age was 68 years (range 41-90). Fifty-one per cent were in stage I, 9% in stage II and 40% in stage III. The presenting features and the survival of the 61 (26%) patients who were first admitted to a division of Hematology of a University Hospital (group HEM) were compared with those of the 170 (74%) patients who were referred to 16 divisions of Internal Medicine at General and County Hospitals (group INT). In the latter group, the patients were older (p = 0.002), had a poorer performance status ( p = 0.0001 ), a higher frequency of renal failure (p = 0.006) and anemia (p = 0.02) and higher beta2 microglobulin levels (p = 0.01). Median survival of group HEM patients did not differ significantly from group INT patients, if all stages were considered, but stage II and III patients of group INT had a significantly shorter median survival than advanced stage patients of group HEM (12 vs. 35 months, p = 0.01). If those older than 65 years or with unfavourable prognostic factors at presentation were excluded, prolonged survival of group INT patients was observed and the curves of the two groups did not differ significantly anymore. These results show that the patients recruited by a specialized centre may represent a selected population with better prognostic factors and younger age and this may affect analysis of clinical trials. Participation of minor centres in clinical trials may considerably contribute in improving interpretation of results of therapy in myeloma and be more representative of the entire population.     

Multiple myeloma--diagnosis, prognostic factors and treatment

The problem of diagnosis, prognostic factors and the efficacy of therapies were investigated in 330 patients with multiple myeloma (MM) and 51 patients with benign monoclonal gammopathy (BMG)/monoclonal gammopathy of undetermined significance (MGUS). Seven out of 51 patients with BMG/MGUS were transformed into MM. The mean time to the transformation was 61.6 months. M protein level in these patients had been gradually and constantly increasing until the transformation in contrast with stable level in non-transformed patients. In MM there was one year difference between median survival from the time of diagnosis and start of chemotherapies. It depended on the deferral of treatment in patients with stage I myeloma. No difference of survival time was found between initial and differed therapy for stage I myeloma. Earlier therapy is not advantageous in this stage. Stages and immunoglobulin classes of MM were prognostic factors. Stage I or IgG myeloma had the longest survival and stage III or BJP myeloma had the shortest one. The new protocol, DMVM plus natural interferon alpha therapy induced high complete remission rate of 37.1% in initial treatment patients. The survival rate at three years from the treatment was 70%.     

Survival of multiple myeloma patients who are potential candidates for early high-dose therapy intensification/ autotransplantation and who were conventionally treated

PURPOSE: To analyze the outcome of patients with multiple myeloma (MM) who were potential candidates for early high-dose therapy (HDT) intensification followed by autotransplantation from a series treated with conventional chemotherapy. PATIENTS AND METHODS: From January 1985 through December 1989, 487 patients with symptomatic MM were entered onto a randomized study to compare melphalan and prednisone (MP) versus vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) /vincristine, carmustine (BCNU), doxorubicin, and prednisone (VBAP). The sub-group of 77 patients who could have been candidates for early intensification with HDT followed by stem-cell support (ie, < 65 years of age, stage II or III disease, performance status < 3, and objective or partial response to initial chemotherapy) are the subjects of this report. RESULTS: Seventy-seven of 487 patients could have been candidates for early intensification. The median age was 56 years (range, 27 to 64). At diagnosis, 12% had abnormal renal function, 16% hypercalcemia, and 42% serum beta 2-microglobulin level > or = 6 mg/L; 62% had stage III disease at diagnosis. Thirty-six patients were initially treated with MP and 41 with VCMP/VBAP. The median response duration to initial chemotherapy was 22 months, and the actuarial probability of being in continued first response at 5 years was 14%. After a median follow-up time of 58 months, 59 patients have died, one was lost to follow-up evaluation, and 17 are still alive 69 to 119 months after initial chemotherapy. The median survival time from initiation of treatment was 60 months and from the time when autotransplantation would be considered, 52 months. The only independent prognostic parameter for survival was renal function at diagnosis. CONCLUSION: The median survival time of patients with MM who are less than 65 years of age and who respond to initial chemotherapy is 5 years. This survival duration is similar to that reported in selected series of patients given early HDT and stresses the importance of ongoing randomized trials to determine the role of HDT in the treatment of younger myeloma patients.     

Prognostic factors of multiple myeloma

Multiple myeloma is a heterogeneous disease with survival ranging from a few months to many years. Several clinical parameters (S beta 2-M) are a direct expression of the tumor burden and have been shown by univariate analysis to be related to patient survival. Durie and Salmon developed a myeloma staging system that analyzed the presenting clinical features, response to treatment and survival duration. But this classification is not related to the intrinsic malignancy (labeling index). Many new parameters (genetic alterations, plasma cell evaluation; serum marqueurs, immune dysregulation) related to patient response to chemotherapy and survival duration have been identified. However, they have not yet been included in standard staging and compared with the recognized prognostic parameters in multivariate analysis. There is a need to create a new international myeloma staging system based on biological features of the disease.     

Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution

BACKGROUND: Twenty percent of patients with multiple myeloma (MM) have renal failure. OBJECTIVE: To analyze the presenting features, the response to therapy, and the factors associated with renal function recovery and survival in 94 patients with MM and renal failure. PATIENTS AND METHODS: Medical records of patients from our institution with MM and renal failure diagnosed between January 1969 and December 1994 were reviewed. The statistical methods consisted of Kaplan-Meier survival curves, the log-rank test, logistic regression analysis, and the Cox proportional hazards model for survival analysis. RESULTS: Renal failure was observed in 94 (22.2%) of 423 patients. Patients with renal failure had more advanced disease than the others. Patients with renal failure had a lower response rate to chemotherapy than those with normal renal function (39% vs 56%; P<.001). However, when patients dying within the first 2 months of treatment were excluded, no significant differences in the response rate were found between patients with renal failure and those with normal renal function. Renal function recovery was observed in 26% of patients. Serum creatinine level (<354 micromol/L [<4 mg/dL]), serum calcium level (> or =2.88 mmol/L [> or = 11.5 mg/dL]), and amount of proteinuria (< 1 g/24 h) were associated with renal function recovery. Patients who recovered renal function had a median survival of 28 months vs 4 months for those with nonreversible renal failure (P<.001). In the multivariate analysis, only serum creatinine level (P=.003) and response to chemotherapy (P<.001) were correlated with survival. CONCLUSIONS: Renal failure was present in almost one fourth of patients with MM. Patients with reversible renal failure had longer survival than those not recovering renal function. When patients dying within the first 2 months of treatment were excluded, the response rate was not affected by renal function. Factors associated with renal function recovery were degree of renal failure, presence of hypercalcemia, and amount of proteinuria. Response to chemotherapy and severity of renal failure were the only independent factors associated with survival.     

Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma

Virtually no progress has been made during more than 2 decades of clinical trials for multiple myeloma (MM) involving standard therapy (ST). Recent studies suggest that dose intensification requiring hematopoietic stem cell support results in higher complete response (CR) rates and extended disease control. "Total Therapy" (TT) consisting of noncross-resistant induction regimens, followed by a double autotransplant (AT) procedure, was administered to 123 untreated patients with symptomatic MM. Upon hematologic recovery, interferon (IFN) maintenance (3 million units [MU]/m2 subcutaneously thrice weekly) was given until disease recurrence/progression. Results were compared with the outcome of untreated patients receiving ST according to Southwest Oncology Group (SWOG) trials. One hundred sixteen pair mates were selected from both TT and among 1,123 patients to match for the major prognostic features. TT induced CR in 40% of all 123 patients (intent-to-treat). By 12 months, 7% had died, including 4% from treatment-related complications. With a median follow-up of 31 months, median durations of event-free survival (EFS) and overall survival (OS) are 49 and 62+ months, respectively. Abnormalities of chromosomes 11q and 13 were associated with inferior outcome, whereas CR within 6 months after induction was a favorable prognostic feature for both EFS and OS. In comparison to ST, TT induced higher PR rates (85% v 52%, P < .0001) (CR rates not available on SWOG trials) and extended EFS (49 v 22 months, P = .0001) and OS (62+ v 48 months, P = .01). Compared to ST, dose intensification with double AT markedly augments tumor cytoreduction, effecting not only higher CR rates but also significantly extending EFS and OS in previously untreated patients with MM.     

Systemic lupus erythematosus in children: the complex problems of diagnosis and treatment encountered in 101 such patients at the Mayo Clinic

Between 1945 and 1970, 101 children (86 girls and 15 boys) with systemic lupus erythematosus were evaluated at the Mayo Clinic. Only 9 children were less than 9 years old at the time of diagnosis. The most frequent presenting complaint was arthralgia; fever, fatigue, and a "butterfly" malar rash also were common. Renal involvement, found in more than 76 per cent of patients, was a prognostically poor sign. The overall survival of children with renal involvement is improved by the use of adequate steroid therapy.     

Intraoperative abandonment of ileal pouch to anal anastomosis--the Mayo Clinic experience

BACKGROUND: Completion of the ileal pouch to anal anastomosis (IPAA) is neither always possible nor advisable based on intraoperative findings. This study was undertaken to document the incidence of and reasons for intraoperative abandonment of IPAA in a series of over 1,700 attempts. STUDY DESIGN: A retrospective review of the Mayo Clinic surgical index from January 1981 through December 1995. Patients with the preoperative diagnosis of chronic ulcerative colitis or familial adenomatous polyposis for whom IPAA was planned but not completed are the subject of this report. Comparison is made to patients with a completed IPAA from the Mayo Clinic IPAA registry. RESULTS: During a 15-year period, 1,789 IPAA attempts were made. Intraoperative abandonment occurred in 74 (4.1%). Patients in whom the operation was abandoned were older than patients in whom it was not (38 versus 33 years, p < 0.01), with age older than 40 years conferring a relative risk of 1.87 versus age younger than 40 (95% confidence interval, 1.19-2.94%). IPAA was abandoned for technical reasons in 32 (43%), intraoperative diagnosis of Crohn's disease in 27 (36%), colorectal cancer in 10 (14%), mesenteric desmoid in 3 (4%), and miscellaneous reasons in 2 (3%) patients. Fifty-one (69%) patients underwent proctocolectomy and ileostomy and 23 (31%) underwent sphincter preserving procedures. Of these, 2 underwent subsequent successful IPAA. CONCLUSIONS: Preoperative counseling for IPAA should include discussion of the risk of intraoperative abandonment (4.1%). Older patients are at increased risk. If the IPAA is abandoned for reversible reasons, preservation of the anal sphincter preserves the option of a subsequent IPAA.     

Plasmablastic morphology--an independent prognostic factor with clinical and laboratory correlates: Eastern Cooperative Oncology Group (ECOG) myeloma trial E9486 report by the ECOG Myeloma Laboratory Group

We studied the prognostic significance of plasmablastic (PB) multiple myeloma (MM) in Eastern Cooperative Oncology Group Phase III trial E9486. Two reviewers independently reviewed 453 cases. They agreed on 37 PB (8.2%) cases and 416 non-PB cases, achieving an 85% concordance (P < .0001). These PB cases had significantly lower hemoglobin and serum albumin levels, higher calcium and beta 2-microglobuin levels, and higher percentage BM plasma cells (PC) by immunofluorescence. They had higher bone marrow PC labeling indices, higher serum soluble interleukin-6 receptor (sIL-6R) levels, and a higher probability of ras mutations. Three treatment regimens were used: vincristine, bis-chloro-ethyl nitrosourea (BCNU) melphalan, cyclophosphamide, and prednisone (VBMCP) alone; VBMCP with added cyclophosphamide (HiCy); or recombinant interferon alpha 2 (rIFNalpha2). Although the numbers are low, patients with PB had a significantly lower response rate versus non-PB MM when treated with VBMCP (treated, 47.1% v nontreated, 66.5% [P = .015]). Patients with nonresponding PB had a significantly higher progression rate than non-PB cases (30.6% v 11.8% [P < .0001]), especially with VBMCP alone (35.3% v 15.8% [P = .002]), and with added HiCy (37.5% v 9.8% [P < .0001]), but not with added rIFNalpha2. Event-free and overall survival of PB MM was shorter (median years, 1.1 v 2.7 and 1.9 v 3.7, respectively [P < .0001 for both]). In multivariate analysis, PB classification was also highly prognostic. There is no survival difference between the patients who were classified as PB by both reviewers versus patients classified as PB by only one reviewer. We conclude that PB MM is a discrete entity associated with more aggressive disease and shortened survival. Tumor cell ras mutations and increased sIL-6R may contribute to a higher proliferation rate and reduced survival. There were significant improvements in response and progression with the addition of HiCy and rIFNalpha2 to VBMCP, but the numbers were small and improved survival could not be shown.     

Maintenance treatment with interferon alpha-2b in multiple myeloma: a prospective randomized study from PETHEMA (Program for the Study and Treatment of Hematological Malignancies, Spanish Society of Hematology)

The objectives of the present study were to investigate whether interferon alpha (IFN) maintenance could prolong response duration and survival in patients with multiple myeloma (MM) in objective response and to analyze the characteristics of relapse and subsequent survival. From January 1991 to November 1994, 92 patients from the Spanish Cooperative Group PETHEMA with MM in objective response after 12 courses of VCMP/VBAP chemotherapy were randomized to receive IFN maintenance vs no treatment until relapse. Prognostic factors at diagnosis were similar in both groups. IFN was administered at a starting dose of 3 mU/m2 three times per week. The IFN toxicity was moderate with granulocytopenia and fatigue being the most common adverse effects. Median duration of response from randomization until relapse was 13 months in the IFN group vs 7.7 months in the no treatment arm (P = 0.042). Median survival from randomization was 38.8 months for patients given IFN vs 32.7 months for those allocated to the no treatment arm (P = 0.12). Features at relapse were similar in patients who received IFN maintenance and in those assigned to no treatment. Finally, survival from relapse was identical in both groups. In summary, our results show a significant prolongation of response in patients maintained with IFN with no significant influence on survival. In addition, in our series features at relapse and subsequent outcome were similar in both groups.     

Survival analysis in patients with cutaneous malignant melanoma

INTRODUCTION: Cutaneous malignant melanoma (MM) takes only 3% of all malignant tumours of the skin, but for reason of its increased frequency and pronounced tendency to rapid growth and metastases, it causes 60% of total lethal outcomes due to malignant tumours of the skin [1]. Primary MM is a diagnostic problem because of the great variety of its clinical features. Asymmetric configuration, irregular border, speckled color(r)diameter of more than 6 mm, and elevation of the surface, suggest suspicion of malignant alteration, but even then misdiagnosis is possible. For the final diagnosis of MM histopathological confirmation is necessary. The method to use is the extensive excisional biopsy of the lesion and its borders [2]. Histopathological diagnosis is based on microscopic findings which include: histogenetic type of MM, tumour thickness according to Breslow, level of invasion according to Clark, presence of ulceration, grade of lymphocyte infiltration, mitote rate, type of cells, presence of melanin in cells [2, 3]. PATIENTS AND METHODS: A five-year survival of patients with cutaneous malignant melanoma (MM) was studied according to sex, age and distinct features of the tumour: site, type of initial therapy, stage of the disease, time from the first signs of the disease to diagnosis of MM, histological findings (histogenetic type, Breslow's tumour thickness, Clark's level of invasion, presence of ulceration, degree of lymphocyte infiltration, number of mitoses, type of cells, intensity of pigmentation) and presence of metastases. The retrospective study included 336 patients with cutaneous MM. There were 185 female (55.1%) and 151 male patients (44.9%), aged 14-83 years, mean age 48.8 years, who were treated at the institute of Oncology and Radiology in Belgrade from 1978 to 1990. The mean follow-up was 60 months (1-144 months). Melanoma in situ had 16 (4.1%) patients. Stage I had 45 patients (14.1%), stage II 163 (48.5%), stage III 83 (24.7%) and stage IV 29 (8.6%) patients. Acral location on hands and feet had 40 (11.9%) patients, on head and neck 36 (10.7%), on the trunk 146 (43.5%) and on the extremities (except hands and feet) 114 (33.9%) patients. Nodular melanoma (NM) was the most frequent histogenetic type revealed in 150 (44.6%) patients, superficial spreading melanoma (SSM) in 105 (31.1%) patients, acral melanoma (AM) in 39 (11.5%) and lentigo malignant melanoma (LMM) in 32 (9.4%) patients (Table 1). Five-year survival rate was calculated according to Kaplan-Meier's method and significance of the difference between some categories was tested by Long-Rank's test; the significance less than 0.05 was accepted. RESULTS: Statistically highly significant differences in a five-year survival (p < 0.01) were related to sex p = 0.0005, age p = 0.0017, tumour site p = 0.0025, initial therapy p = 0.0036, stage of MM p = 0.0000, histological features of the tumour p = 0.0000 and presence of metastases p = 0.0000. A better five-year survival prognosis was found in female patients (64.5%) compared to male patients 44.5%, aged 27-46 years (87.3%) compared to patients younger than 26 years (43.5%); patients with melanoma on the extremities (except hands and feet) had a better five-year survival (66.7%) compared to patients younger than 26 years (43.5%); patients with melanoma on the extremities (except hands and feet) had a better five-year survival (65.7%) compared to patients with melanoma on the trunk or acral melanoma (47.3%). Higher survival was recorded in the group of patients with the tumour 1.5-3 mm thick, in whom the tumours was excised and regional nodes dissected as the primary therapy (66.9%) compared to those who underwent excision of the tumor only (48.8%). A five-year survival of patients with MM in situ was 100% for those in stage I; 85% in stage II; 42% in stage III, 16% and 0% in stage IV. The patients in whom the diagnosis of MM was established within 10 months after the first signs of the disease had significa     

Clinical evaluation of myeloma osteoclastic bone lesions: II. Induced hypocalcemia test using salmon calcitonin

Acute effects of salmon calcitonin (SCT) were tested by an SCT induced hypocalcemia test (SCT delta Ca test) in 70 cases of multiple myeloma (MM) (including 52 untreated patients) with bone involvement. Response to SCT in terms of maximum induced hypocalcemia (M delta Ca) was compared to normal controls (NC) and correlated with the main presenting features and clinical status. Acute effects are significantly more marked in MM than in NC (p less than .001). There is a good correlation with the extent of lytic bone lesions (p less than .01), the presence of hypercalcemia (p less than .02) and the myeloma cell mass (p less than .05). After correction for bone involvement response to SCT (M delta Ca) was stronger in IgA lambda MM than in IgG kappa (p less than .01). It is of particular interest that acute effects are significantly more marked in cases of active disease than in non-active disease. We conclude that the SCT delta Ca test might be of practical value in the management of MM.     

Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics

We report on a series of 26 patients diagnosed with primary (de novo) plasma cell (PC) leukemia (PCL) in whom we analyzed the clinicobiologic characteristics of the disease together with the immunophenotype, DNA cell content, proliferative index, and numeric chromosomal aberrations of the neoplastic PC, and compared them with 664 multiple myeloma (MM) patients at diagnosis. The median age, sex ratio, and bone lesion extension were similar, but PCL cases displayed a higher prevalence of clinical stage III, extramedullary involvement, and Bence Jones cases, with fewer IgA cases than for MM patients. In addition, according to several prognostic indicators (beta2-microglobulin serum level, proportion of S-phase PCs, proteinuria, calcium serum level, lactate dehydrogenase [LDH] and renal function), the incidence of adverse prognostic factors was significantly higher in PCL versus MM. Immunophenotypic expression was similar for CD38, CD138, CD2, CD3, CD16, CD10, CD13, and CD15, but PCL differed from MM in the expression of CD56, CD9 HLA-DR, CD117, and CD20 antigens. Twenty-two PCL cases were diploid and one was hypodiploid, while most MM cases (57%) showed DNA hyperdiploidy. With the fluorescent in situ hydridization (FISH) technique, 12 of 13 PCL cases displayed the numeric aberrations, -13 (86%), +/-1 (57%), +18 (43%), and -X in women (25%), but they lacked several numeric aberrations usually found in MM such as +3, +6, +9, +11, and +15. PCL cases had a lower overall response to therapy than MM cases (38% v 63%, P =.01332). Among PCL patients, a trend for a worse response was observed in cases treated with melphalan and prednisone (MP) versus polychemotherapy. Overall survival was significantly worse in PCL versus MM patients (8 v 36 months, P <.0001), but it was significantly better in PCL patients treated with polychemotherapy versus MP (18 v 3 months, P =.0137). By contrast, MM patients did not show significant differences in overall survival according to the treatment used, MP or polychemotherapy. Ten variables seemed to predict survival in PCL patients, but only the beta2-microglobulin level and S-phase PCs retained an independent value in multivariate analysis. In summary, our study illustrates that PCs from PCL display singular phenotypic, DNA cell content, and cytogenetic characteristics that lead to a different disease evolution versus MM.     

Primary systemic amyloidosis with delayed progression to multiple myeloma

BACKGROUND: Primary systemic amyloidosis (AL) and multiple myeloma both are clonal plasma cell proliferative disorders. Although 10-15% of patients with myeloma have coexisting primary amyloidosis, it is unusual for patients with primary amyloidosis to progress to myeloma at a later date. The authors describe a case series of six patients in whom such progression occurred. METHODS: A computerized search was done of the medical records of all patients seen at the Mayo Clinic between January 1, 1960 and December 31, 1994 with a diagnosis of AL. Of 1596 patients with AL, 6 patients (age range, 60-74 years; median age, 68 years) with biopsy-proven AL were reviewed in whom delayed (at least 6 months after the diagnosis of AL) progression to multiple myeloma occurred. RESULTS: At the time of the diagnosis of AL, none of the six patients had evidence of multiple myeloma. The dominant manifestation of AL was peripheral neuropathy in three patients and cutaneous AL, renal AL, and amyloid arthropathy in one patient each. The diagnosis of multiple myeloma was made 10-81 months after the diagnosis of AL, based on the demonstration of multiple osteolytic lesions (4 patients) or marked bone marrow infiltration (> or = 50%) by plasma cells (5 patients). Two patients had received chemotherapy (melphalan and prednisone) for AL. Five patients received chemotherapy (four patients) or high dose methylprednisolone (one patient) after the diagnosis of multiple myeloma. Five patients died, and the median actuarial survival after the diagnosis of multiple myeloma was 20 months. Multiple myeloma was the cause of death in four patients; one patient died of systemic amyloidosis. In 2 patients death occurred within 3 months. CONCLUSIONS: AL occasionally progresses to overt multiple myeloma. These cases usually occur in patients without significant cardiac or hepatic AL who live long enough to develop multiple myeloma.     

多发性骨髓瘤中14q32易位与13q14缺失的相关性研究

目的 研究多发性骨髓瘤(MM)常见的分子遗传学异常14q32易位与13q14缺失及其与临床指标的关系.方法 采用间期荧光原位杂交(I-FISH)技术应用RB1、D13S319和LSI IGHC/IGHV探针检测49例MM患者骨髓标本中RB1基因、13q14.3缺失及14q32易位,结合临床资料作统计分析.结果 49例MM患者有26例(53.1%)检测到14q32易位,25例(51.02%)存在13q14缺失(其中18例检测到13q14.3缺失,9例存在RB1缺失).Spearman相关分析显示,14q32易位多见于浆细胞比例高的患者(r=0.316,P=0.27),与患者年龄、国际分期系统(ISS)分期、免疫球蛋白分型、β2微球蛋白及肾损害无相关性(P＞0.05).结论 13q14缺失及14q32相关的易位在MM中发生率均较高,两者有密切相关性;14q32易位的MM患者浆细胞百分比明显升高,14q32易位的检测可作为预测MM预后的指标.     

The use of intravenous intermediate dose melphalan and dexamethasone as induction treatment in the management of de novo multiple myeloma

The variable absorption of melphalan from the gastrointestinal tract results in response rates between 40 and 60%. High dose melphalan increases response rates but at the cost of increased morbidity and mortality. We have investigated intravenous intermediate dose melphalan and dexamethasone in the treatment of patients presenting with de novo multiple myeloma with the object of reducing toxicity while preserving an improved response rate compared to oral melphalan and prednisolone. The results show that this treatment can be delivered safely on an outpatient basis in patients up to the age of 78 yr; 82% of patients achieved an objective response and 30% a complete haematological and clinical remission. Median overall survival for the whole group is 37 months.     

Comparison of interleukin-1 beta expression by in situ hybridization in monoclonal gammopathy of undetermined significance and multiple myeloma

We investigated whether interleukin-1beta (IL-1beta) is differentially expressed in plasma cells from monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients because IL-1beta appears to play a major role in the development of lytic bone lesions, the major clinical feature distinguishing MGUS from myeloma. In situ hybridization (ISH) for IL-1beta was performed using bone marrow aspirates from 51 MM, 7 smoldering MM, 21 MGUS, and 5 normal control samples. Using the ISH technique IL-1beta mRNA was detectable in the plasma cells from 49 of 51 patients with active myeloma and 7 of 7 patients with smoldering myeloma. In contrast, 5 of 21 patients with MGUS and 0 of 5 normal controls had detectable IL-1beta message. Bone lesions were present in 40 of the 51 MM patients analyzed, and all 40 patients had IL-1beta mRNA by ISH. These results show that greater than 95% of MM patients but less than 25% of MGUS patients are positive for IL-1beta production. In the future, continued follow-up of IL-1beta positive and negative MGUS patients should determine whether aberrant expression of plasma cell IL-1beta is predictive of those MGUS patients that will eventually progress to active myeloma.