A Case of Multiple Myeloma with Metachronous Chronic Myeloid Leukemia Treated Successfully with Bortezomib, Dexamethasone, and Dasatinib

The coexistence of multiple myeloma and chronic myeloid leukemia in a single patient is a very rare event that has been reported very infrequently in the literature. We report a case of a patient who developed chronic myeloid leukemia four years after his diagnosis with multiple myeloma. Historically, no link between the two malignancies has been identified. This synchronous existence complicates the treatment plan for these patients, and there is a lack of evidence on the best therapeutic approach. Our patient was successfully treated with a combination of bortezomib, dexamethasone, and dasatinib, which he tolerated well for eleven months until he eventually succumbed to cardiac complications and pulmonary hypertension leading to his death

Myelofibrosis involving lymph node: a novel cytogenetic abnormality in a mimicker of mesenchymal neoplasm

A case of primary myelofibrosis involving lymph node and with a novel cytogenetic abnormality [del (18) (p11.2-3)] is reported. The abnormalities are identical among specimens from the lymph node, peripheral blood, and bone marrow that were analyzed years apart. Additionally, we show that the infiltrate by dysplastic megakaryocytes in the lymph node morphologically mimics a metastatic mesenchymal neoplasm, even when the clinical history myelofibrosis was known

Hypercalcemia in B-Cell Chronic Lymphocytic Leukemia: Report of a Case and Review of the Literature.

Abstract A 53 year old man with Rai stage IV CLL was being treated with R-HyperCVAD when he presented between cycles with fatigue, lethargy and pancytopenia. Clinical examination revealed diffuse adenopathy and splenomegaly. Serum calcium was 13.6 mg/dl, phosphorus level was 2.7 mg/dl, and alkaline phosphatase was 54 U/L. PTH was 4 Units/L (10–65), PTHrP &amp;lt; 0.2 pmole/L (0–1.9), 1–25 (OH) Vitamin D &amp;lt; 10pgm/ml (22–67). Quantitative immunglobulins: IgA 10 mg/dl, IgG 252 mg/dl, IgM 50 mg/dl. Immunofixation revealed a faint IgG lambda paraprotein. There were no lytic lesions on skeletal survey. Bone marrow biopsy revealed focal large cell transformation (Richter’s syndrome). Cytogenetics revealed 3 metaphases with complex cytogenetic abnormalities, indicating clonal evolution. The hypercalcemia resolved with appropriate therapy, but despite subsequent treatment with CAMPATH, he died 2 weeks after diagnosis. A review of reported patients with CLL and hypercalcemia in the literature was performed from 1980 onwards using MEDLINE and PubMed; only those cases in which clinical aspects, biochemistry, PTH levels, imaging studies and concurrent pathology (if obtained) were documented, are summarized in this analysis (n=13). Rai stage: I n=1, II n=4, III n=3, IV n=5. Immunoreactive PTH levels were low or normal in 100% of patients. In 5 cases in which it was measured, 1–25 (OH) Vitamin D levels were not elevated. PTHrP was normal in 2 cases and elevated in 1. In nine patients, multiple lytic bone lesions were present on skeletal radiology. Two patients had osteopenia without lytic lesions. Two had no lytic lesions. Six of ten patients had evidence of transfomation on lymph node and/or bone marrow biopsy performed at the time of evaluation for hypercalcemia. Prognosis was poor (range 0.5–12 months) with only one patient surviving post allo-transplant. In conclusion, hypercalcemia in CLL is rare. Osteolytic lesions are present in the majority of cases. PTH levels are low, and thus this hormone is not mediating the hypercalcemia. The evidence is also against a role of elevated Vitamin D. Histological transformation is seen in half of the cases. Survival is poor after diagnosis of hypercalcemia. The mechanisms(s) of the osteolysis and hypercalcemia remain to be defined.</jats:p

A Case of Multiple Myeloma with Metachronous Chronic Myeloid Leukemia Treated Successfully with Bortezomib, Dexamethasone, and Dasatinib

The coexistence of multiple myeloma and chronic myeloid leukemia in a single patient is a very rare event that has been reported very infrequently in the literature. We report a case of a patient who developed chronic myeloid leukemia four years after his diagnosis with multiple myeloma. Historically, no link between the two malignancies has been identified. This synchronous existence complicates the treatment plan for these patients, and there is a lack of evidence on the best therapeutic approach. Our patient was successfully treated with a combination of bortezomib, dexamethasone, and dasatinib, which he tolerated well for eleven months until he eventually succumbed to cardiac complications and pulmonary hypertension leading to his death

Abstract P3-05-16: The effect of HER-2/neu inhibition on prolonging clinical benefit with fulvestrant treatment for metastatic estrogen receptor positive breast cancer patients treated with trastuzumab

Abstract Background: Fulvestrant is a well-established treatment for postmenopausal patients with estrogen receptor (ER) positive metastatic breast cancer, and some patients experience prolonged clinical benefit exceeding one year. HER2 activation is a major cause of endocrine resistance, and cross-talk between HER2/neu and ER coactivator MED1 regulates tamoxifen resistance in breast cancer cells. (Cancer Res 2012 1;72(21):5625-34.). In a xenograft mouse model, suppression of MED1 enhanced tumor growth inhibition by fulvestrant in HER2/neu overexpressing breast cancer cells (PLoS One 20123 30;8(7)). Objective of study: To determine if blocking the HER2/neu receptor with trastuzumab can improve response to fulvestrant. Methods: This was an IRB approved record review of patients from three medical oncologists with biopsy-proven ER+ metastatic breast cancer treated with fulvestrant. Demographic data collected included age at diagnosis, type and stage of cancer, original and metastatic ER, progesterone receptor (PR), and HER2/neu biomarkers, and site(s) of metastasis, and primary local and systemic treatment. All patients with HER2/neu positive primary tumors received trastuzumab. The duration of fulvestrant therapy was calculated. Time to clinical disease progression on fulvestrant was measured as a surrogate for duration of clinical benefit. Based on the median duration of therapy of 425 days, patients were divided into two groups: Short Treatment (&amp;lt; 425 days) versus Prolonged Treatment (&amp;gt;425 days). Results: One hundred metastatic ER+ fulvestrant treated breast cancer patients with documented duration of therapy were identified. There was no difference between the Short and Prolonged Treatment Groups in regards to age, sites of metastases, or use of adjuvant endocrine or chemotherapy. Eighty five patients had recorded HER2/neu tumor status. All 11 of 85 (13%) patients with documented HER2/neu positive primary tumors received trastuzumab. Patients with HER2/neu positive tumors tended to have longer durations of fulvestrant therapy (772 (51-1911) days (median (range)) compared to HER2/neu negative patients (360 (60-2739) days, p=0.059). Only 2 of 45 (4%) tumors from the Short Treatment Group were HER2/neu positive, while 9 of 40 Prolonged Treatment Group patients with documented HER2/neu status were positive (Fisher’s exact test p&amp;lt;0.021). Patients with HER2/neu positive tumors were more likely to experience prolonged responses to therapy with an odds ratio of 6.2 (1.26 to 30.92 95% confidence interval, p=0.0249). Conclusion: Overexpression of HER2/neu in tumors from ER+ metastatic breast cancer patients treated with trastuzumab was associated with a prolonged response to fulvestrant therapy. Citation Format: Mahmoud Charif, Elyse E Lower, Diane Kennedy, Harriet Kumar, Shugufta Khan, Neetu Radhakrishnan, Xiaoting Zhang. The effect of HER-2/neu inhibition on prolonging clinical benefit with fulvestrant treatment for metastatic estrogen receptor positive breast cancer patients treated with trastuzumab [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-05-16.</jats:p

Response to Rituximab, Cyclophosphamide and Dexamethasone as Initial or Salvage Therapy in Low Grade Lymphoma and Immune Hemolytic Anemia.

Abstract BACKGROUND: The combination of dexamethasone, cyclophosphamide, and rituximab (RCD) have documented activity in lymphoproliferative disorders without severe side effects and shows significant results in the setting of AIHA (auto immune hemolytic anemia) in CLL (chronic lymphocytic leukemia). We conducted a retrospective study of the response to RCD in low grade lymphoproliferative disorders and in AIHA at our institution. METHODS: Between December 1998 and June 2006, 17 patients completed therapy after a median of 6 cycles of RCD (rituximab 375 mg/m2 i.v. on Day 1, dexamethasone 40 mg intravenously [i.v.] or [p.o.] on Days 1–4, cyclophosphamide at a dose of 750 mg/m2 i.v. on Day 2). Data regarding patient characteristics, disease pathology, stage, IPI scores, prior treatments, response using standard disease response criteria and flow cytometric and/or molecular studies where appropriate, and any recurrences were recorded. Stage IV responders with undocumented post treatment bone marrows were classified as PR (partial response). RESULTS: The median age of the patients was 63 years (range: 28 – 80 years), 42% were male; (9/17) 52% had previously untreated disease; and (9/17) 52% had follicular lymphoma, 35% had other indolent lymphomas or CLL (2 marginal zone lymphoma (1 salvage), 1 mantle zone lymphoma, 1 waldenstroms macroglobulinemia requiring frequent plasmapheresis, 1 small cell lymphocytic lymphoma and 1 CLL) and 2 had steroid resistant AIHA. Median international prognostic index/follicular lymphoma international prognostic index (IPI/FLIPI) score for the malignant lymphomas was 2 (range: 0–3). Objective responses (OR) and complete responses (CR) were observed in (16/17) 94% and (11/17) 64%, respectively. For patients with follicular lymphoma, the respective OR and CR ratios were 5/5 (100%) and 3/5 (60%) as first line therapy, and 4/4 (100%)and 2/4 (50%) as salvage therapy. Both patients with heavily pretreated AIHA responded completely and have not relapsed. The median progression free survival (PFS) was 18 months (range: 1–58 months) and median overall survival (OS) was 28 months (range: 1 – 78 months). The PFS for follicular lymphomas was a median of 19months (range: 6 – 55months), with median OS of 45 months (range: 6 – 78 months). Both patients with heavily pretreated AIHA achieved CR without relapse. Recurrence of disease did not correlate with the FLIPI/IPI. Side effects were minimal and included grade II – III neutropenia, hyperglycemia and steroid induced insomnia. CONCLUSIONS: RCD is active as initial or salvage therapy in patients with low grade lymphoproliferative disorders and is highly effective in steroid refractory AIHA with minimal side effects. Addition of rituximab prior to moderate doses of cytoxan and dexamethasone significantly enhances the response rates. This chemotherapeutic combination with a low side effect profile appears to produce significant responses for low grade lymphomas and may translate into better long term outcomes compared to previously utililized regimens. Further studies are needed to evaluate whether this regimen may improve the outcome of patients with low grade lymphomas. Summary of data Pathology (no: of pts) OR (pt no:) CR(pt no:) PFS (months) Recurrence(pt no:) Untreated follicular lymphoma (5) 5 3 19 1 Pre treated follicular (4) 4 2 12 3 Other indolent lymphoma (6) 5 4 23 0 AIHA(2) 2 2 14.5 0</jats:p