Mohamad Khawandanah

Distant skin metastases as primary presentation of gastric cancer.

Distant gastric metastasis to the skin is uncommonly a presenting symptom, although nonspecific paraneoplastic syndromes with dermatologic manifestation including diffuse seborrheic keratoses (Leser-Trelat sign), tripe palms, and acanthosis nigricans have been described in the literature. We report here the case of a 49-year-old woman with gastric adenocarcinoma who presented with cutaneous metastasis as an initial symptom. In our case, metastatic skin lesions responded significantly to EOX chemotherapy (epirubicin+oxaliplatin+capecitabine) despite progression of systemic disease. In similar presentations, a high index of clinical suspicion and skin biopsy are important.

DMSO induced myocardial infarction during allogeneic cryopreserved bone marrow transplant

Dear Editor, Allogeneic hematopoietic stem cell transplantation (HSCT) has been successfully used to treat high-risk hematologic malignancies and marrow failure syndromes. Being able to cryopreserve hematopoietic stem cells (HSC) is one of the crucial reasons for the success in allogeneic HSCT. To allow long-term storage of HSC, dimethyl sulfoxide (DMSO) is the most frequently used cryopreservative agent as it prevents disruptive crystal to be formed intracellularly during the freezing process, and thus preventing cell death. However, infusion of peripheral blood or marrow-derived HSC cryopreserved with DMSO can be associated with toxic reactions such as vomiting, cardiac dysfunction, anaphylaxis, and acute renal failure [1]. The grade of toxicity experienced by patients is related to the amount of DMSO present in the stored cells [1, 2]. Current standard technique of cryopreservation of HSC is controlled rate of freezing and storage in liquid nitrogen, but this is associated with high cost and DMSO toxicity when used at 5–10 % concentration. On the other hand, cryopreservation at −80 °C, by uncontrolled rate of freezing with only 3– 5 % DMSO, can be satisfactory for long-term hematopoietic and immunologic reconstitution [3]. Stem cell-related cardiac events are difficult to prove with certainty but commonly thought to be related to cell lysis, red blood cells viscosity, hypothermic shock, acute volume expansion, and DMSO toxicity [4]. Cardiovascular DMSO toxicity can manifest itself as bradycardia, hypertension, and cardiac arrhythmia [5] and rarely as coronary vasospasm or myocardial infarction [6] (Table 1). We report on the case of a 43-year-old male with glucose-6phosphate dehydrogenase (G6PD) deficiency who underwent allogeneic-matched sibling marrow transplant using myeloablative preparative regimen with cyclophosphamide and total body irradiation for acute lymphoblastic leukemia (ALL) in first complete remission. His cardiac history included two brief episodes of paroxysmal atrial fibrillation in 2006 controlled with beta-blocker with no underlying cardiac disease identified. The pre-transplant cardiopulmonary assessment was unremarkable, including baseline electrocardiogram (EKG) (QTc=409), pulmonary function tests (FEV1=4.04 L and DLCO=93 %), and nuclear ventriculography (left ventricular ejection fraction=65 %). Transplanted marrow stem cells for infusion was collected and frozen prior to administration and consisted of 2.22×10/kg CD34+ HSC stored in six cryopreservation bags (600 mL, 6 bags) with 10 % DMSO (1 g/kg). Marrow HSC were infused according to standard institutional protocol per FACT guideline (Foundation for the Accreditation of Cellular Therapy) and premedication with hydrocortisone, acetaminophen, and diphenhydramine was administered 20 min prior to the transplant. Following infusion of the fourth aliquot, the patient experienced severe headache, nausea, chest tightness, diaphoresis, restlessness, episode of hypertension, and bradycardia (44/min). His cardiac monitor showed atrial fibrillation. His vital signs were blood pressure 180/100 mm Hg, heart rate 70/min, temperature 36 °C, and respiratory rate of 14 breaths per minute. EKG showed M. Khawandanah : S. Nabeel : B. Ahmad : J. Holter Charkrabarty : C. Yuen :G. Selby Hematology-Oncology Section, Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

Ibritumomab tiuxetan (Zevalin) and elevated serum human anti-murine antibody (HAMA)

Ibritumomab Tiuxetan (Zevalin) is an anti CD-20 murine monoclonal antibody linked to the radio-isotope 90-yttrium (90Y) by the chelator Tiuxetan. It is FDA approved for treatment of relapsed low grade or follicular B-cell Non-Hodgkins Lymphoma (NHL) or newly diagnosed follicular NHL following an initial response to first-line chemotherapy. Patients may develop Human Anti-Murine Antibodies (HAMA), following exposure to murine antibodies. There is a concern for development of hypersensitivity reactions with Ibritumomab, especially in patients with an elevated HAMA titer. Here we describe a case of a 66 year old male with elevated HAMA titer successfully treated with Zevalin without any hypersensitivity reactions. Existing literature supports our observation that Zevalin can be safely used in most patients with elevated HAMA titers.

Efficacy of High-Dose Therapy and Autologous Hematopoietic Cell Transplantation in Gray Zone Lymphoma: A US Multicenter Collaborative Study

High-dose therapy (HDT) and autologous hematopoietic cell transplantation (auto-HCT) has been anecdotally prescribed in gray zone lymphoma (GZL), showing encouraging efficacy. We conducted a multicenter retrospective study aimed at assessing outcomes after auto-HCT in 32 patients with GZL treated at 9 transplantation centers in the United States. The median age of patients at transplantation was 38 years (range, 18 to 70 years), and the majority were male (n = 21; 66%). The median number of lines of therapy before transplantation was 2 (range, 1 to 4). BEAM was the most commonly prescribed regimen (n = 23; 72%). The median duration of follow-up for surviving patients was 34 months (range, 1 to 106 months). Median overall survival (OS) was not reached. The 3-year progression-free survival (PFS) and OS for all patients were 69% and 78%, respectively. Three-year PFS and OS were 100% for patients who received only 1 line of therapy before auto-HCT versus 65% (PFS, P = .25) and 75% (OS, P = .39) for those receiving >1 line. The cumulative incidence of relapse/progression was 4% at 1 year post-transplantation and 31% at 3 years post-transplantation. The 3-year nonrelapse mortality was 0%. These findings suggest that HDT and auto-HCT is an effective treatment in patients with GZL. Our findings ideally require confirmation in a larger cohort of patients, preferably in the setting of large prospective multicenter randomized controlled trials. However, we acknowledge that such studies could be difficult to conduct in patients with GZL owing to the diseases rarity. Alternatively, a multicenter prospective study that includes tissue banking and a data registry is warranted to help better understand the biology and natural history of the disease.

Autoimmune hemolytic anemia and thrombocytopenia attributed to an intrauterine contraceptive device.

Evans syndrome is a rare condition manifested by combined autoimmune hemolytic anemia (AIHA) and thrombocytopenia or neutropenia. It is often associated with other autoimmune disorders, immunodeficiencies, and non‐Hodgkins lymphoma.

Refractory Classical Hodgkin Lymphoma Presenting with Atypical Cutaneous Involvement and Diagnosis of ZZ Phenotype Alpha-1 Antitrypsin Deficiency

Cutaneous Hodgkin lymphoma is a rare condition. Specific neoplastic involvement can be primary (confined to the skin) or secondary to systemic involvement (metastatic). Cutaneous involvement by HL usually occurs late in the course and is associated with poor prognosis; however in some cases it can exhibit indolent behavior. Skin involvement with nonspecific cutaneous findings may represent a paraneoplastic syndrome. We describe a case of 46-year-old white male patient presented with rash and lymphadenopathy which led to the diagnosis of stage IVE mixed cellularity classical Hodgkin lymphoma with skin involvement. His disease was refractory to multiple lines of chemotherapy including (1) AVD (doxorubicin/bleomycin/dacarbazine), (2) brentuximab, and (3) bendamustine, he later achieved complete remission with (4) GCD (gemcitabine/carboplatin/dexamethasone) salvage regimen. Bleomycin was not given secondary to poor pulmonary function tests. His treatment was complicated after AVD with multiple pneumothoraces which unmasked the diagnosis of ZZ phenotype alpha-1 antitrypsin (ATT) deficiency. Simultaneous existence of Hodgkin lymphoma and ATT is rarely reported.

A Case of Acute Myeloid Leukemia with a Previously Unreported Translocation (14; 15) (q32; q13)

Background. We hereby describe what we believe to be the first reported case of t (14; 15) (q32; q13) associated with acute myeloid leukemia (AML). Methods. PubMed, Embase, and OVID search engines were used to review the related literature and similar published cases. Case. A47-year-old female presented in December 2011 with AML (acute myelomonocytic leukemia) with normal cytogenetics; molecular testing revealed FLT-3 internal tandem duplication (ITD) mutation, while no mutations involving FLT3 D385/I836, NPM1 exon 12, or KIT exons 8 and 17 were detected. She was induced with 7 + 3 (cytarabine + idarubicin) and achieved complete remission after a second induction with high-dose cytarabine (HiDAC) followed by uneventful consolidation. She presented 19 months after diagnosis with relapsed disease. Of note, at relapse cytogenetic analysis revealed t (14; 15) (q32; q13), while FLT-3 analysis showed a codon D835 mutation (no ITD mutation was detected). She proved refractory to the initial clofarabine-based regimen, so FLAG-idarubicin then was used. She continued to have persistent disease, and she was discharged on best supportive care. Conclusion. Based on this single case of AML with t (14; 15) (q32; q13), this newly reported translocation may be associated with refractory disease.