Mustaqeem A. Siddiqui

Absolute lymphocyte count predicts overall survival in follicular lymphomas

The peripheral blood absolute lymphocyte count (ALC) recovery after autologous stem cell transplantation has been shown to be an independent prognostic factor for survival for different haematologic malignancies. The role of ALC at diagnosis for follicular (grades 1 and 2) lymphomas (FL) on survival is not well described. The primary objective of this study was to assess the role of ALC on overall survival (OS) in FL patients. Of 1104 FL patients, 228 patients were originally diagnosed, followed, and had all treatment at the Mayo Clinic from 1984 and 1999, were evaluated. The median follow‐up was 89 months (range: 8·35–248). ALC as a continuous variable was identified as a predictor for OS [Hazard ratio (HR) = 0·74, P < 0·04]. ALC ≥ 1·0 × 109/l (n = 164) predicted a longer OS versus ALC < 1·0 × 109/l (n = 64; 175 vs. 73 months respectively, P < 0·0001). When compared with the Follicular Lymphoma International Prognostic Index (FLIPI), ALC was an independent prognostic factor for OS by multivariate analysis (HR = 0·677, P < 0·0001). These data suggest a critical role of FL patients’ immune status at diagnosis on survival.

The High Cost of Cancer Drugs and What We Can Do About It

Last year, ipilimumab (Yervoy; Bristol-Myers Squibb, New York, NY) was approved by the Food and Drug Administration (FDA) for the treatment of metastatic melanoma. The benefit in survival over and above standard treatment arms was 3.7 months in previously treated patients and 2.1 months in previously untreated patients.1,2 The cost:

A factor found in the igg fraction of serum of patients with paraneoplastic bilateral diffuse uveal melanocytic proliferation causes proliferation of cultured human melanocytes

120,000 for 4 doses. As staggering a figure as that is, the drug is hardly alone in its lofty price. We believe that the immense cost of contemporary cancer drugs signals even greater costs for future drugs (Table).

Impact of New Drugs and Biologics on Colorectal Cancer Treatment and Costs

Purpose: To determine if there is a factor in the serum of patients with bilateral diffuse uveal melanocytic proliferation (BDUMP) that causes melanocytic proliferation. Methods: Human melanocytes and melanoma cells were grown and exposed to serum or plasma of patients with BDUMP, other neoplastic conditions, or control media. Preliminary studies using serum were conducted in an unmasked fashion. In addition, IgG-depleted and IgG-enriched plasma was also tested in a similar fashion. Experiments using plasma were conducted triple masked. To show that the proliferation was melanocyte selective, human dermal fibroblasts, keratinocytes, and ovarian cancer cells were treated with plasma of the BDUMP cases or controls, and the effect of this exposure on their proliferation was quantified. Results: At 72 hours, the serum of BDUMP patients caused statistically significant increased proliferation of normal human melanocytes. Further studies at 6 days demonstrated similar findings. In addition, melanocytes grown in BDUMP serum exhibited a disorganized morphology with foci of multilayered cells. Cultured melanoma cells also showed statistically significant increase in growth in serum from BDUMP patients compared with controls. Masked plasma studies further confirmed these findings and showed that the IgG fraction appeared to contain the melanocyte growth-stimulating factor. The human fibroblasts, keratinocytes, and ovarian cancer cells did not show an increase in growth with the BDUMP plasma treatment. Conclusion: Patients with BDUMP have a factor in the IgG fraction that selectively causes melanocyte proliferation. How it causes proliferation of human melanocytes and melanoma cells needs to be further elucidated.

Cost‐effectiveness analysis of early vs. late autologous stem cell transplantation in multiple myeloma

PURPOSE To compare medical expenditures of patients receiving old and new colorectal cancer (CRC) regimens. STUDY DESIGN USING CLAIMS DATA, WE IDENTIFIED TWO COHORTS OF PRIVATELY INSURED PATIENTS DIAGNOSED WITH CRC: first, those diagnosed before new treatment introduction (January 1, 2002, to December 31, 2002), and second, those diagnosed after new treatment introduction (June 1, 2004, to May 31, 2005). CRC diagnosis was identified using International Classification of Diseases-9 codes 153.xx, 154.xx, and 159.0. First- and second-line chemotherapy regimens were identified. Treatments and expenditures were then observed for up to 2 years after initial diagnosis. METHODS We estimated multivariate models to measure changes in cost with changes in treatment regimen. Approval dates of new regimens were used as natural experiments. RESULTS New regimens, such as fluorouracil, leucovorin, and oxaliplatin (FOLFOX), have rapidly replaced the most prevalent preperiod product (ie, fluorouracil/leucovorin). Changes in treatment have caused large increases in total expenditure, primarily through increases in chemotherapy prices. FOLFOX alone has increased total average cost by 14%. New treatments have not substituted other medical services; rather, they have indirectly raised costs through nonstandard regimen use and increases in second-line treatment use. We found no evidence that expenditure effects were driven by changes in follow-up duration. CONCLUSION New CRC treatments have increased both regimen choice and expenditures. New regimens have primarily increased expenditures through direct treatment costs; we observed no offsetting expenditure reductions.

Prevalence, incidence and survival of smoldering multiple myeloma in the United States

Autologous stem cell transplant (ASCT) is the current standard of care for most patients with multiple myeloma (MM) who are transplant eligible, yet the timing of ASCT is disputed due to a similar overall (OS) and progression‐free survival with an early ASCT (eASCT) or a delayed ASCT (dASCT) approach.

Teaching NeuroImages: Diagnostic utility of FDG-PET in neurolymphomatosis

Smoldering multiple myeloma (SMM) is currently defined as MM without evidence of impending (⩾60% clonal bone marrow plasma cells, serum involved to uninvolved free light chain ratio of ⩾100 with absolute involved light chain level of ⩾100 mg/L, or >1 focal lesion on magnetic resonance imaging ⩾5 mm in size) or active (hypercalcemia, renal insufficiency, anemia or bone lesion – crab signs) end organ damage, which are considered indications for treatment.1 Although institutional studies show that ~8–20% of patients with MM are smoldering at the time of diagnosis,2 the actual prevalence of SMM in the United States (US) is unknown. Epidemiologic studies have been difficult to perform due to the lack of International Classification of Diseases (ICD) codes differentiating smoldering from active MM.

The role of high-dose chemotherapy followed by peripheral blood stem cell transplantation for the treatment of multiple myeloma

A 70-year-old woman with a history of non-Hodgkin lymphoma presented with left-sided facial pain. MRI of the face, orbit, and neck was negative (figure). A week later, she developed hypesthesia in a V3 distribution. Repeat MRI was again nondiagnostic but fluorodeoxyglucose (FDG)-PET showed increased uptake along the left V3 branch of the trigeminal nerve, as well as in the parotid gland. Biopsy of the left parotid confirmed recurrent lymphoma.

Prognostic impact of combined NPM1+/FLT3− genotype in patients with acute myeloid leukemia with intermediate risk cytogenetics stratified by age and treatment modalities

The management of multiple myeloma has changed significantly over the past 10 years. The results obtained with conventional chemotherapy were disappointing; however the use of high dose therapy (HDT) and stem cell transplantation has significantly improved survival. Autologous, allogeneic and tandem transplantation, along with different conditioning regimens, have been studied in an attempt to optimise and further improve outcomes. This review summarises the role of stem cell transplantation in multiple myeloma. The advent of novel therapies such as thalidomide, lenalidomide and bortezomib have started to redefine the role of peripheral stem cell transplantation, however, further study is needed to better understand how to most effectively use these agents in multiple myeloma in conjunction with HDT.

Prevalence and survival of smouldering Waldenström macroglobulinaemia in the United States

The prognostic impact of combined NPM1+/FLT3- genotype is not well defined in elderly patients with acute myeloid leukemia (AML), and in the setting of different treatments, such as cytotoxic chemotherapy (Chemo), hematopoietic cell transplantation (HCT), or hypomethylating agents (HMA). Eighty-two elderly (age >60 years) and 78 younger adults (age 18-60 years) with newly diagnosed intermediate-risk cytogenetic AML were classified according to the presence or absence of NPM1+/FLT3- genotype, and treatments (Chemo vs. HCT. vs. HMA). The estimated 3-year overall survivals (OS) in elderly (N=17) and younger adults (N=13) with NPM1+/FLT3- treated with Chemo were 59% and 64%, respectively (P=0.71). In the absence of NPM1+/FLT3-, younger adults had a superior OS when treated with HCT than with Chemo (P<0.0001), but elderly showed no survival advantage with HCT after adjustment for baseline covariates. Elderly patients lacking NPM1+/FLT3- had a comparable OS when treated with Chemo vs. HMA (P=0.79). Combined NPM1+/FLT3- is associated with a favorable prognosis irrespective of age in AML patients treated with Chemo. In the absence of NPM1+/FLT3- genotype, younger adults undergoing HCT have an improved survival, while elderly have comparable OS when treated with Chemo vs. HMA.