A rare case of acute lymphoblastic leukemia in a patient with light chain (AL) amyloidosis treated with lenalidomide.

Lenalidomide belongs to a novel class of drugs called Immunomodulators which are now being used for the treatment of plasma cell dyscrasias with variable degrees of efficacy and toxicity. Though Second Primary Malignancies (SPM) have been a concern with its use, the benefits of the treatment outweigh the risks. The leukemogenic risk seems to be potentiated especially when combined with alkylating agents and the SPMs documented are predominantly myeloblastic. To date there are no reported cases of new lymphocytic leukemias in AL amyloidosis, regardless of whether undergone treatment or not. We present a case of AL amylodosis who was treated with lenalidomide and subsequently developed acute lymphoblastic leukemia.

Effects of commercially available soy products on PSA in androgen-deprivation-naïve and castration-resistant prostate cancer.

OBJECTIVE: No standard therapeutic option exists for men with prostate cancer who have failed local therapy, have no gross metastatic disease, and whose only manifestation of disease is a rising prostate-specific antigen (PSA) level. Soy products are able to affect PSA kinetics in some men with prostate cancer, and this effect has been attributed to the decreased expression of the androgen receptor and other mechanisms. METHODS: We treated 10 men with rising PSA levels after radical prostatectomy and salvage radiotherapy with commercially available soy products. Scans revealed no gross metastatic disease. Three men also had been receiving androgen-deprivation therapy (ADT) and had rising PSA levels that were consistent with castration-resistant (CR) disease. We reported the results of this modality on PSA levels, PSA kinetics, and the duration of PSA response. RESULTS: Responses occurred in 4 of 7 (57%) patients with ADT-naïve disease and 1 of 3 (33%) patients with CR disease. The median duration of treatment response was 24 months. The overall clinical benefit, therefore, was noted in 5 of 10 (50%) patients. Therapy was well tolerated. CONCLUSIONS: Our findings are fairly congruent with what has been described in the literature on the use of this modality in prostate cancer. We used commercially available soy products. We also show that soy can provide benefit in CR prostate cancer. Our clinical experience suggests that soy supplementation using commercially available soy products can have durable beneficial effects on PSA levels and PSA kinetics in some men with prostate cancer.

Two patients with germline mutations in both BRCA1 and BRCA2 discovered unintentionally: a case series and discussion of BRCA testing modalities.

When a family is known to have a BRCA mutation, genetic testing for family members is typically limited to single site analysis of the known mutation. The exception to this is in Ashkenazi Jewish families, where testing for the three common Ashkenazi Jewish BRCA mutations is recommended. We report two cases, one without Ashkenazi Jewish ancestry and one with maternal Ashkenazi Jewish ancestry, who underwent Comprehensive BRACAnalysis testing despite known BRCA1 mutations in family members. Testing identified the BRCA1 mutation previously identified, and a second mutation in BRCA2. These cases raise the question of whether or not Single Site BRACAnalysis for a known familial BRCA mutation is always the appropriate test when testing an affected individual. The implications of missing a second mutation are discussed.

Transformation of the 5q- syndrome to acute lymphoblastic leukemia: a report of two cases and review of the literature.

Myelodysplastic syndrome (MDS) with an isolated deletion of the long arm of chromosome 5 (5q- syndrome) is a distinct subtype of MDS with an indolent course that rarely transforms to acute leukemia. Deletion of the long arm of chromosome 5 has also been reported in rare cases of de novo B-lymphoblastic leukemia. We present two cases of 5q- syndrome with a similar and unusual course of transformation to lymphoblastic leukemia while on Lenalidomide. These two patients achieved an initial response; however, later acquired a second cytogenetic abnormality, became refractory to treatment and evolved into acute leukemia. At the time of transformation, both patients had recurrence of the 5q- abnormality. Review of the literature and the mechanisms of transformation of the 5q-syndrome into an acute leukemia are discussed. Although the relationship between the events in our cases remains unclear, the intriguing similarity between the two cases raises a question whether immune modulators can alter the natural course of MDS. To our knowledge, no similar cases were previously reported in the literature.

Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice.

Tyrosine kinase is a key enzyme activity utilized in many intracellular messaging pathways. Understanding the role of particular tyrosine kinases in malignancies has allowed for the design of tyrosine kinase inhibitors (TKIs), which can target these enzymes and interfere with downstream signaling. TKIs have proven to be successful in the treatment of chronic myeloid leukemia, renal cell carcinoma and gastrointestinal stromal tumor, and other malignancies. Scattered reports have suggested that these agents appear to affect blood glucose (BG). We retrospectively studied the BG concentrations in diabetic (17) and nondiabetic (61) patients treated with dasatinib (8), imatinib (39), sorafenib (23), and sunitinib (30) in our clinical practice. Mean declines of BG were dasatinib (53 mg/dL), imatinib (9 mg/dL), sorafenib (12 mg/dL), and sunitinib (14 mg/dL). All these declines in BG were statistically significant. Of note, 47% (8/17) of the patients with diabetes were able to discontinue their medications, including insulin in some patients. Only one diabetic patient developed symptomatic hypoglycemia while on sunitinib. The mechanism for the hypoglycemic effect of these drugs is unclear, but of the four agents tested, c-kit and PDGFRß are the common target kinases. Clinicians should keep the potential hypoglycemic effects of these agents in mind; modification of hypoglycemic agents may be required in diabetic patients. These results also suggest that inhibition of a tyrosine kinase, be it c-kit, PDGFRß or some other undefined target, may improve diabetes mellitus BG control and it deserves further study as a potential novel therapeutic option.

Bevacizumab demonstrates prolonged disease stabilization in patients with heavily pretreated metastatic renal cell carcinoma: a case series and review of the literature.

There are now a variety of therapies approved for the treatment of metastatic renal cell carcinoma (RCC). These include the immunotherapeutics, alfa-interferon, and interleukin-2, and agents that target the vascular endothelial growth factor receptor (VEGFR) via its tyrosine kinase, such as sorafenib, sunitinib, and pazopanib, or the mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus. Bevacizumab, a monoclonal antibody directed against the ligand, VEGF, has shown activity against RCC as a single agent in patients who had failed prior cytokine therapy and as first line therapy in combination with interferon. The activity of bevacizumab in patients who had received and failed prior therapy has not been described. We report our experience in 4 patients with metastatic RCC who had failed prior cytokine, TKI, and mTOR inhibitors who were treated with bevacizumab as single agent therapy. These heavily pretreated patients sustained very prolonged periods of stable disease (median of 12 months) with very little toxicity and excellent quality of life. The activity of this agent in patients who had failed prior therapies directed against the VEGFR and mTOR suggests that therapy targeting the ligand, VEGF, is still a viable approach in these patients and deserves further study.

Current immunotherapeutic strategies in malignant melanoma.

The basis of immunotherapy for melanoma is the existence of melanoma-associated antigens that can be targeted by the immune system. Identification of many of these antigens has enabled investigators to develop a wide array of immunotherapy strategies for the treatment of melanoma. Although several of these strategies have been shown to induce antitumor immune responses in some patients, robust clinical responses have been observed less frequently. With exciting recent advancements in this field, however, there is promise of generating potent immunologic responses and translating them more consistently into durable clinical responses. This article reviews several current approaches to immunotherapy for melanoma and describes the key role that surgeons play in advancing this area of oncology.