Mark J. Fesler

High-Dose Interleukin-2 (HD IL-2) Therapy Should Be Considered for Treatment of Patients with Melanoma Brain Metastases

A retrospective review was performed on patients with stable melanoma brain metastases treated with HD IL-2 therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course, maximum 2 courses) from January 1999 to June 2011 at Saint Louis University. There were 5 men and 3 women; median age was 52.2 years (26.8–61.1 years). One patient started treatment with lung lesions only (after resection of melanoma brain disease) and experienced partial response. Seven patients had brain metastases at treatment initiation. Median overall survival (mOS) for entire cohort (n = 8) was 8.7 months (2.1 to 19.0 months). All patients with brain metastases at first dose (n = 7) showed progressive disease; mOS was 6.7 months (range 2.1–18.2 months) for this group. Patients received radiosurgery and whole brain radiation before and after HD IL-2 therapy. One patient had symptoms suggestive of neurotoxicity. A history of alcohol abuse was revealed during admission. The patients symptoms improved with initiation of an alcohol withdrawal protocol. In this analysis, patients with melanoma brain metastases received HD IL-2 without treatment-related mortality. We think that HD IL-2 should be considered as a treatment option in patients with melanoma brain metastases who are otherwise eligible for therapy.

Narrowing down the common deleted region of 5q to 6.0 Mb in blastic plasmacytoid dendritic cell neoplasms

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy. Simple and complex recurrent cytogenetic abnormalities have been reported, which demonstrate predominantly genomic losses, of which deletions of 5q are the most frequent aberrations in BPDCN with or without cutaneous manifestation; however, the gene responsible for the disease remains unknown. Using microarray-based molecular characterization, a recent study on several cases of BPDCN with the 5q deletion identified a large, common deleted region (CDR) of 29 Mb that contains several possible candidate genes. We report on a 67-year-old female patient who presented with leukemic BPDCN without skin involvement and had a deletion of 5q and a t(6;8)(p21;q24). By oligo-array-comparative genome hybridization (a-CGH) method, the genomic coordinations of the 5q deletion demonstrated unique breakpoints reported for the first time. Through mapping with those published cases using the same a-CGH method, the CDR was reduced from 29 Mb to 6 Mb, which excluded the previous candidate genes and highlighted an excellent biological gene: the HINT1 gene. Moreover, a molecular cytogenetic characterization of the translocation t(6;8) was performed in search for a novel gene fusion that could be associated with tumor progression.

Modified array-based comparative genomic hybridization detects cryptic and variant PML-RARA rearrangements in acute promyelocytic leukemia lacking classic translocations.

Acute promyelocytic leukemia (APL) is typically defined at the molecular level by a reciprocal translocation of the promyelocytic leukemia (PML) and retinoic acid receptor &agr; (RARA) genes. An accurate diagnosis of APL is critical for appropriate choice of therapy and prognostic assessment. Cryptic and variant rearrangements in APL are discoverable by a variety of molecular methods including fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction, or gene sequencing. Rare reports of FISH-negative APL harboring cryptic rearrangements of PML-RARA detected by reverse transcriptase polymerase chain reaction or sequencing have been described. Here, we describe the detection of cryptic or variant PML-RARA rearrangements by translocation-based comparative genomic hybridization (tCGH), a recently described modification of traditional CGH technology that facilitates the detection of balanced translocations by means of the linear amplification of a potential translocation breakpoint region(s), in 2 unusual cases of APL. One tumor lacked detectable t(15;17) by karyotype and FISH, and the other tumor lacked the typical morphologic and immunophenotypic features of APL and had a variant 3-way translocation involving PML and RARA. PML-RARA translocations were identified by tCGH in both cases providing confirmation of the diagnosis of APL. These data emphasize the benefit of using complementary molecular methods including tCGH for detecting cryptic and variant PML-RARA translocations in unusual cases of APL.

Procarbazine-induced hepatotoxicity: case report and review of the literature.

Procarbazine hydrochloride is an oral alkylating agent primarily used as a component of chemotherapy regimens for Hodgkins lymphoma, as well as in regimens for primary central nervous system lymphoma and high‐grade gliomas. Although the prescribing information for procarbazine lists hepatic dysfunction as a potential adverse reaction, we found only one published report with a probable link between procarbazine and liver injury. We describe a 65–year‐old man who developed liver injury due to procarbazine during salvage chemotherapy for non‐Hodgkins lymphoma. The patient had no preexisting liver disease, his lymphoma was without hepatic involvement, and no liver injury developed after initial chemotherapy with R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Due to relapse of his non‐Hodgkins lymphoma, salvage chemotherapy with C‐MOPP‐R (cyclophosphamide, vincristine, procarbazine, prednisone, and rituximab) was administered, and the patient developed fever and amino‐transferase level elevation during the second cycle. After discontinuation of all drug therapy, exclusion of other potential etiologies, and resolution of hepatic injury, the patient was rechallenged with procarbazine and again experienced fever with aminotransferase level elevation. His aminotransferase levels promptly returned to normal after discontinuation of procarbazine, and he experienced no further evidence of liver disease. Use of validated scoring systems of drug‐induced liver injury indicated a definitive association between the patients hepatic injury and procarbazine. Based on our experience with this patient, periodic assessment of hepatic function, as suggested in the package insert, is recommended in patients receiving procarbazine.

Histiocytic sarcoma: The first reported case of primary Esophageal involvement

To the Editor: We present a case of primary esophageal invasion by histiocytic sarcoma (HS), which to the best of our knowledge has not been reported in the literature to date.

Active Shingles Infection as Detected on 18F-FDG PET/CT

We present the case of a 56-year-old male with a history of recurrent follicular lymphoma undergoing chemotherapy with multiple 18F-FDG PET-CT studies at an outside facility. He developed a painful erythematous, pruritic rash in the left back requiring a visit to the emergency room. He was diagnosed and treated for Varicella zoster infection. He then presented to our imaging center 2 months later for a follow up 18F-FDG PET/CT study. Imaging demonstrated a cutaneous band of increased metabolic activity in the upper back following a dermatomal distribution. This was confirmed to be in the same area as the treated Varicella zoster eruption. A subsequent follow up 18F-FDG PET-CT scan 4 months later to confirm tumor resolution demonstrated the abnormal band of uptake in the back had resolved. This case illustrates the significance of being aware of this entity and to distinguish it from metastasis, especially in patients with a known history of malignancy.

Marked bone marrow hypoplasia associated with sorafenib-induced marrow blast clearance in two patients with FLT3-ITD acute myeloid leukemia

Sorafenib (Nexavar, Bayer HealthCare Pharmaceuticals, Wayne J) is a multi-targeted tyrosine kinase inhibitor (TKI) which inhibits he FLT3 (fms-like tyrosine kinase receptor-3) protein on acute yeloid leukemia (AML) blasts. Given the efficacy of sorafenib at nducing remissions in relapsed/refractory FLT3-ITD mutated AML 1], it is anticipated that its use will continue to increase in both elapsed and frontline settings. While peripheral blood cytopeias are a recognized complication of sorafenib even in the solid umor setting, we are aware of no reports describing the bone arrow hypoplasia with profound peripheral blood cytopenias in atients administered sorafenib for FLT3-ITD mutated AML. We escribe two cases of relapsed FLT3-ITD mutated AML who develped peripheral blood cytopenias on compassionate-use sorafenib, nd both patients were found to have bone marrow hypoplasia with last clearance.

Acute myeloid leukemia induction with cladribine: Outcomes by age and leukemia risk

Acute myeloid leukemia (AML) induction traditionally includes seven days of cytarabine and three days of an anthracycline (7 + 3). Because of evidence of increased efficacy of cladribine combined with this regimen, we conducted a retrospective analysis of 107 AML patients treated with idarubicin, cytarabine and cladribine (IAC) at our institution. Complete remission (CR) occurred in 71%, with overall response of 79%. One-year survival overall was 59%, with 47% (27/57) among patients ≥60 years old and 72% (36/50) in those <60 (Relative Risk [RR] 1.9, 95% CI 1.2-3.2). Median overall survival was 17.3 months in all patients and Cox proportional hazard ratio (HR) for death was 2.2 (95% CI 1.3-3.6) for age ≥60 years compared to <60 years. One year survival was 100% among favorable NCCN risk patients versus 64% in intermediate-risk and 35% in poor-risk patients (p < 0.001). HR for death in intermediate- risk (4.2, 95% CI 1.5-12) and poor-risk (8.4, 95% CI 3.0-24) compared to favorable risk AML was higher than that associated with age ≥60 years (HR 2.2). We conclude that IAC is an effective AML induction regimen, NCCN leukemia risk predicts survival better than age in our population, and high intensity regimens can be justified in selected older patients.

Bendamustine and rituximab for indolent B-cell non-hodgkin lymphoma in patients with compensated hepatitis C cirrhosis: a case series.

Hepatitis C is a risk factor for indolent B-cell lymphoproliferative disorders, and clinicians will likely encounter patients with chronic liver disease concurrent with these disorders. A dearth of information exists on use of bendamustine in patients with indolent B-cell lymphoproliferative disorders and hepatic impairment, and therefore treatment of these conditions concurrently is a dilemma. We describe 2 patients with indolent B-cell lymphoproliferative disorders and hepatitis C-related cirrhosis who were effectively and safely treated with a combination of rituximab and bendamustine.

Zosteriform Rash: Another Manifestation of “The Internist's Tumor”

Introduction Cutaneous metastases are a well-described manifestation of renal cell carcinoma, although papillary renal cell carcinoma appears to be less commonly associated with cutaneous metastasis than clear cell histology. Zosteriform rash has a papular or vesicular appearance in a dermatomal distribution, and it has been associated with primary cutaneous malignancies as well as metastases from hematologic and solid cancers. Zosteriform rash as a manifestation of cancer has been reviewed by other researchers; however, we are aware of no reports of renal cell carcioma that caused this unusual manifestation of malignancy, and we etail the clinical course of one of our patients in this report.