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