Low 25(OH) vitamin D3 levels are associated with adverse outcome in newly diagnosed, intensively treated adult acute myeloid leukemia.

Background: Several studies have suggested that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in patients with acute myeloid leukemia (AML).

Methods: Vitamin D levels were evaluated in 97 consecutive, newly diagnosed, intensively treated patients with AML. MicroRNA expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome.

Myelodysplastic syndromes and autoimmune diseases--case series and review of literature.

Our objective was to recognize the association of autoimmune diseases (AD) in patients with myelodysplastic syndromes (MDS) and understand how this association could affect prognosis and management of both diseases. We describe our cohort of 10 patients and 34 patients reported in the English literature in addition to ten cohort studies. Interestingly, four cases showed improvement in AD after 5-azacitidine treatment.

Is obesity a prognostic factor for acute myeloid leukemia outcome?

Obesity adversely affects outcome in pediatric acute lymphocytic leukemia and acute myeloid leukemia (AML). We asked if obesity, measured by body mass index (BMI), affected outcome in 329 adult AML patients treated with high-dose cytarabine and idarubicin-containing regimens administered according to actual body weight. Age ≥ 60, unfavorable karyotype, secondary AML, and positive smoking status had adverse impact on overall survival in a multivariate analysis, while BMI did not.

Smoking adversely affects survival in acute myeloid leukemia patients.

Smoking adversely affects hematopoietic stem cell transplantation outcome. We asked whether smoking affected outcome of newly diagnosed acute myeloid leukemia (AML) patients treated with chemotherapy. Data were collected on 280 AML patients treated with high-dose cytarabine and idarubicin-containing regimens at Roswell Park Cancer Institute who had smoking status data at diagnosis.

Phase 1 study of arsenic trioxide, high-dose cytarabine, and idarubicin to down-regulate constitutive signal transducer and activator of transcription 3 activity in patients aged <60 years with acute myeloid leukemia.

Background: Constitutive activation of signal transducer and activator of transcription-3 (STAT3) was detected in blasts from approximately 50% of patients with acute myeloid leukemia (AML) and was correlated with an adverse outcome. In vitro treatment of AML blasts with arsenic trioxide (ATO) down-regulated STAT3 activity within 6 hours associated with a reduced viability within 48 hours.

Methods: A phase 1 clinical trial to evaluate the biologically effective dose and/or the maximally tolerated dose (MTD) of ATO in vivo in conjunction with high-dose cytarabine (Hidac) and idarubicin (Ida) in patients with AML aged <60 years was conducted.

Myeloid blastic transformation of myeloproliferative neoplasms--a review of 112 cases.

Blastic transformation of myeloproliferative neoplasms (MPN) is still poorly understood. We describe a cohort of 23 Roswell Park Cancer Institute (RPCI) patients and 89 additional cases from the English literature for whom biologic features were described. We initially compared our 23 patients to the 89 cases from the literature.

Bortezomib in combination with pegylated liposomal doxorubicin and thalidomide is an effective steroid independent salvage regimen for patients with relapsed or refractory multiple myeloma: results of a phase II clinical trial.

Novel agents have demonstrated enhanced efficacy when combined with other antimyeloma agents especially dexamethasone. The steroid doses employed in myeloma regimens are often poorly tolerated. Therefore, in a phase II clinical trial we investigated the efficacy of a steroid-free combination including bortezomib, pegylated liposomal doxorubicin and thalidomide (VDT regimen).

Treating octogenarian and nonagenarian acute myeloid leukemia patients--predictive prognostic models.

Background: Treating the octogenarian and nonagenarian patients who have acute myeloid leukemia (AML) with intensive chemotherapy is controversial. Several models to predict outcome were proposed, including the use of a comorbidity index. However, it is unclear whether the Charlson comorbidity index (CCI) or the hematopoietic cell transplant comorbidity index (HCTCI) is more sensitive.

Metachronous and synchronous presentation of acute myeloid leukemia and lung cancer.

Smoking is associated with both acute myeloid leukemia (AML) and lung cancer. We therefore searched our database for concomitant presentation of AML and lung cancer. Among 775 AML cases and 5225 lung cancer cases presenting to Roswell Park Cancer Institute between the years January 1992 and May 2008 we found 12 (1.

Acute promyelocytic leukemia after mitoxantrone therapy for multiple sclerosis.

Mitoxantrone is a DNA-topoisomerase 2 inhibitor used as a single agent for treatment of relapsing-remitting or progressive multiple sclerosis (MS). We present here two patients treated with mitoxantrone for MS who subsequently developed acute promyelocytic leukemia (APL). These constitute, to our knowledge, the eighth and ninth reports of APL in patients treated with mitoxantrone for MS.

Therapy-related myelodysplastic syndrome and acute myeloid leukemia following treatment of acute myeloid leukemia: possible role of cytarabine.

Therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/t-AML) have been reported only rarely following treatment of AML. We report five patients treated for de novo AML who developed t-MDS/t-AML, all with chromosome 7 abnormalities, including -7, del(7)(q22q36) and del(7)(p11.22p22).

Translocation (4;11)(p12;q23) with rearrangement of FRYL and MLL in therapy-related acute myeloid leukemia.

Reciprocal chromosomal translocations involving the MLL gene at chromosome region 11q23 are recurring cytogenetic abnormalities in both de novo and therapy-related acute myeloid leukemia (AML) and in acute lymphoblastic leukemia. We report a t(4;11)(p12;q23) with rearrangement of MLL and FRYL (also known as AF4p12), a human homolog to the furry gene of Drosophila, in an adult patient with therapy-related AML after fludarabine and rituximab therapy for small lymphocytic lymphoma and radiation therapy for breast carcinoma. To our knowledge, t(4;11)(p12;q23) has been reported in two previous patients, and MLL and FRYL rearrangement was demonstrated in one of them.

High dose CHOP: a phase II study of initial treatment in aggressive non-Hodgkin lymphoma. Cancer and Leukemia Group B 9351.

Cyclophosphamide and doxorubicin, two important drugs in the treatment of lymphoma, exhibit a relationship between dose and fractional cell kill, and because of their toxicity profiles, they are candidates for significant dose escalation. We performed a phase II trial to determine the response rate, toxicity, and feasibility of escalated doses of both drugs as part of high dose CHOP in diffuse aggressive lymphoma. Patients who had advanced, previously untreated diffuse aggressive lymphomas (IWF E-H) and an International Prognostic Index of intermediate to high risk were eligible.

Acute myeloid leukemia developing during imatinib mesylate therapy for chronic myeloid leukemia in the absence of new cytogenetic abnormalities.

The BCR/ABL tyrosine kinase inhibitor imatinib mesylate produces a high rate of cytogenetic responses in patients with Philadelphia (Ph)-positive chronic myeloid leukemia (CML), but secondary clonal chromosome abnormalities may develop in Ph-negative cells, and acute myeloid leukemia (AML) has been reported in patients with secondary chromosome abnormalities. We report a patient who developed AML during imatinib treatment of Ph-positive CML despite a cytogenetic response and absence of secondary chromosome abnormalities. Thus, development of AML as a rare event in CML patients with cytogenetic responses to imatinib therapy does not depend on the development of secondary cytogenetic abnormalities.

Routine immunophenotyping in acute leukemia: Role in lineage assignment and reassignment.

Diagnostic evaluation of acute leukemia at Roswell Park Cancer Institute has routinely included immunophenotyping by multiparameter flow cytometry. In a retrospective analysis of 646 cases, morphology and cytochemistry established lineage in 612, but not in 34 (5%), of which 26, 5, and 3 were myeloid, undifferentiated, and lymphoid, respectively, based on immunophenotyping. In addition, immunophenotyping changed the lineage assigned based on morphology and cytochemistry in 11 cases (2%); 8 changed from lymphoid to myeloid, and 3 from myeloid to lymphoid.

Isochromosome 1q in a myelodysplastic syndrome after treatment for acute promyelocytic leukemia.

A growing body of literature reports therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) in patients treated successfully for acute promyelocytic leukemia (APL). We report a t-MDS with an isochromosome 1q as a sole abnormality, 47,XY,+1,i(1)(q10), in a 46-year-old man with APL 14 years after he was treated with cytosine arabinosine and daunorubicin. The literature on t-MDS/t-AML after APL therapy and on isochromosome 1q is reviewed.

Genomic profiling of myeloid sarcoma by array comparative genomic hybridization.

Myeloid sarcoma (MS) is a tumor mass of myeloblasts or immature myeloid cells occurring in an extramedullary site. In this study, seven cases of MS [stomach (1), testis (1), skin (2), and lymph node (3)] and 3 synchronous and 1 follow-up bone marrow (BM) samples were studied for genomic abnormalities using array comparative genomic hybridization (array-CGH). Array-CGH construction used approximately 5,400 bacterial artificial chromosome clones from the RPCI-11 library, spanning the human genome.

Comparison of HER2 status by fluorescence in situ hybridization and immunohistochemistry to predict benefit from dose escalation of adjuvant doxorubicin-based therapy in node-positive breast cancer patients.

Purpose: HER2 is a clinically important tumor marker in breast cancer; however, there is controversy regarding which method reliably measures HER2 status. We compared three HER2 laboratory methods: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), to predict disease-free survival (DFS) and overall survival (OS) after adjuvant doxorubicin-based therapy in node-positive breast cancer patients.

Methods: This is a Cancer and Leukemia Group B (CALGB) study, using 524 tumor blocks collected from breast cancer patients registered to clinical trial CALGB 8541.

Human CD4+ effector memory T cells persisting in the microenvironment of lung cancer xenografts are activated by local delivery of IL-12 to proliferate, produce IFN-gamma, and eradicate tumor cells.

The implantation of small pieces of human primary lung tumor biopsy tissue into SCID mice results in a viable s.c. xenograft in which the tissue architecture, including tumor-associated leukocytes, tumor cells, and stromal cells, is preserved in a functional state.

Extra copies of chromosome 2 are a recurring aberration in ALK-negative lymphomas with anaplastic morphology.

The purpose of this study was to evaluate fluorescence in situ hybridization abnormalities of the 2p23 anaplastic lymphoma kinase (ALK) gene loci in lymphomas with anaplastic morphology. We studied 24 anaplastic large cell lymphomas (ALCL) classified by World Health Organization criteria [17 primary nodal/systemic (10 ALK+, 7 ALK-), seven primary cutaneous], and 17 additional non-Hodgkin's lymphomas [one ALK+ B-lineage lymphoma, 14 ALK- diffuse large B-cell lymphomas (seven anaplastic variants, five nonanaplastic, two secondary CD30+), two follicular lymphomas]. ALK- lymphomas with anaplastic morphology showed extra nonrearranged anaplastic lymphoma kinase gene loci (P=0.

Long-term survival with allogeneic stem cell transplant and donor lymphocyte infusion following salvage therapy with anti-CD52 monoclonal antibody (Campath) in a patient with alpha/beta hepatosplenic T-cell non-Hodgkin's lymphoma.

Hepatosplenic T-cell non-Hodgkin's lymphoma (HSTCL) is a rare, aggressive form of NHL, with a median survival of approximately 8 months. We were able to successfully induce complete remission in a patient with alpha/beta HSTCL who was refractory to multiple prior chemotherapy regimens, using the humanized anti-CD52 monoclonal antibody alemtuzumab (Campath). Once disease was controlled, the patient was able to undergo allogeneic stem cell transplantation (SCT), which resulted in complete remission.