Although most of the initial studies in angiogenesis were done on solid tumors, there is now data suggesting the importance of angiogenesis in hematologic malignancies. We estimated bone marrow microvessel density before autologous stem cell transplantation and at the time of response in 13 patients with myeloma (seven complete and six partial responders) using an immunohistochemical stain for factor VIII-related antigen (von Willebrand factor). , P = 0.003. There was no difference in microvessel density at the time of complete or partial response compared to values prior to transplantation. This report confirms that increased angiogenesis is found in myeloma bone marrow prior to transplantation, and suggests that increased angiogenesis persists even after complete response.
We classified 100 cases of myeloma before chemotherapy as mature (28), intermediate (38), immature (19), or plasmablastic (15). The plasmablastic group had an estimated median survival (Kaplan-Meier method) of ten months, compared to 35 months for the other types (P less than .05). Decreased survival in the plasmablastic group was due to more frequent deaths in the first six months. There were no significant differences in survival among the mature, intermediate, and immature groups or among patients with different morphological grade or asynchrony scores. The plasmablastic myeloma group had more frequent renal insufficiency and higher plasma cell labeling indices, which may have contributed to the shorter survival.
The plasma cell labeling index (PCLI) and serum beta 2-microglobulin (beta 2M) are independent prognostic factors in multiple myeloma (MM). Recently, levels of thymidine kinase (TK) and C-reactive protein (CRP) have been shown to have prognostic value. We studied 107 patients with newly diagnosed myeloma to determine whether TK and CRP values added prognostic information not already available using the PCLI and beta 2M. Univariate survival analysis showed prognostic significance for the PCLI, TK, beta 2M, age, serum albumin, and CRP. Multivariate analysis showed that only PCLI and beta 2M have independent prognostic significance. The survival curves were better separated using the PCLI and beta 2M than with other combinations of variables. Among nine patients under age 65 with low PCLI and low beta 2M, eight were alive almost 6 years after starting chemotherapy. These good-risk patients could not be identified by standard clinical features. Although creatinine and calcium were normal, other features such as bone lesions, osteoporosis, fracture, and anemia were present and stage distribution was similar to other patients in the study. In conclusion, PCLI and beta 2M measured at diagnosis are independent prognostic factors. They must be considered when interpreting the results of clinical trials and should be helpful in counseling patients and in designing new trials. When the PCLI and beta 2M values are known, the TK and CRP values do not add useful additional prognostic information.
The plasma cell labeling index (PCLI) and serum beta 2-microglobulin (beta 2M) are independent prognostic factors in multiple myeloma (MM). Recently, levels of thymidine kinase (TK) and C-reactive protein (CRP) have been shown to have prognostic value. We studied 107 patients with newly diagnosed myeloma to determine whether TK and CRP values added prognostic information not already available using the PCLI and beta 2M. Univariate survival analysis showed prognostic significance for the PCLI, TK, beta 2M, age, serum albumin, and CRP. Multivariate analysis showed that only PCLI and beta 2M have independent prognostic significance. The survival curves were better separated using the PCLI and beta 2M than with other combinations of variables. Among nine patients under age 65 with low PCLI and low beta 2M, eight were alive almost 6 years after starting chemotherapy. These good-risk patients could not be identified by standard clinical features. Although creatinine and calcium were normal, other features such as bone lesions, osteoporosis, fracture, and anemia were present and stage distribution was similar to other patients in the study. In conclusion, PCLI and beta 2M measured at diagnosis are independent prognostic factors. They must be considered when interpreting the results of clinical trials and should be helpful in counseling patients and in designing new trials. When the PCLI and beta 2M values are known, the TK and CRP values do not add useful additional prognostic information.
One hundred sixty-eight patients with primary systemic amyloidosis (AL) were identified. Median survival after diagnosis was 12 months and ranged from 4 months for patients presenting with congestive heart failure to 50 months for those presenting with peripheral neuropathy only. Utilizing the proportional-hazards model in a stepwise multivariate fashion to evaluate the simultaneous influence of putative risk factors as of diagnosis revealed that congestive heart failure, urine light chain, hepatomegaly, and multiple myeloma were the major factors adversely affecting survival during the first year after diagnosis. Serum creatinine, multiple myeloma, orthostatic hypotension, and monoclonal serum protein were the most important variables adversely affecting survival for patients surviving 1 year. These models were used to categorize patients according to the variables in the models into low-, moderate-, and high-risk groups for the first year after diagnosis and separately for subsequent years. The influence of these variables on survival is important in stratification of patients randomized to prospective clinical trials.
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