15 O'Reilly R, Hansen JA, Kurzberg J et al. Allogeneic marrow transplants: .... 14 Enzmann DR, Brant-Zawadzki M, Britt RH. CT of central nervous system ...
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above 3.3 kg tended to have an increase in total cellularity, although we have found no published data to either support or refute these data. In conclusion, umbilical cord blood from males with heavier birth weights are more suitable for transplants, although low volume cord blood would be useful for low weight recipients. 1 I Prat1 Regional Blood Transfusion Centre, 1 MC Herna´ndez Umbilical Cord Blood Bank; 2 M Ortiz1 Obstetrics and Gynecology Service; 3 Hematology Service, A Flores2 2 R Gonza´lez de Gor Carlos Haya Regional Hospital, F Sa´nchez1 Malaga, Spain E Terol1 A Galeote1 MD Ruiz3 J Larracoechea2 J Maldonado3
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References 1 Gluckman E, Broxmeyer HE, Auerbach AD et al. Hematopoietic reconstitution in a patient with Fanconi anemia by means of umbilical cord blood from an HLA-identical sibling. New Engl J Med 1989; 17: 1174–1189. 2 Kurtzberg J, Laughlin M, Graham ML et al. Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. New Engl J Med 1996; 335: 157–166. 3 Wagner JE, Rosenthal J, Sweetman R et al. Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. Blood 1996; 88: 795–802. 4 Silberstein LE, Jefferies LC. Placental-blood banking – a new
Unusual presentation of cerebral toxoplasmosis after BMT Toxoplasmosis is a rare but almost always fatal infection following allogeneic bone marrow transplantation (BMT).1 There have been 57 cases of disseminated toxoplasmosis following BMT reported in the literature, and the brain is the most frequently affected organ.1,2 Cerebral toxoplasmosis manifests with focal signs, fever, seizures, headache and altered mental status.3 A CT scan typically shows multiple hypodense lesions in both hemispheres and basal ganglia with nodular or peripheral enhancement after contrast medium infusion.3,4 We report a case of fatal disseminated toxoplasmosis infection presenting as a single cerebral hemorrhagic lesion on the CT scan. An 18-year-old male with a 6-month history of SAA was seropositive for Toxoplasma gondii pre-transplant and received a matched graft from a toxoplasma seronegative donor. Conditioning was cyclophosphamide and busulphan,
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frontier in transfusion medicine. New Engl J Med 1996; 335: 199–201. Rubinstein P, Dobrila L, Rosenfield RE et al. Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution. Proc Natl Acad Sci USA 1995; 92: 10119–10122. Broxmeyer HE, Douglas GW, Hangoc G et al. Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci USA 1989; 86: 3828–3832. Gluckman E, Rocha V, Boyer-Chammard A et al. Outcome of cord-blood transplantation from related and unrelated donors. New Engl J Med 1997; 337: 373–381. Morrison SJ, Wandycz AM, Akashi K et al. The aging of hematopoietic stem cells. Nature Med 1996; 2: 1011–1016. Morrison SJ, Prowse KR, Ho P, Weissman IL. Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity 1996; 5: 207–216. Ferna´ndez MN, Regidor C, Garcı´a J. Transplante con sangre de cordo´n umbilical. Programa educacional de la XXXVIII Reunio´n Nacional de Hematologı´a y Hemoterapia, Ma´laga, 1996, pp 35–42. Garcı´a J, Tugues D, Miralles A, Badell I. La sangre de cordo´n umbilical como fuente de progenitores hematopoye´ticos transplantables. Programa educacional del IV Congreso Nacional de la Sociedad Espan˜ola de Transfusio´n Sanguı´nea, Oviedo, 1993, pp 175–180. Turner CW, Luzins J, Hutchenson C. A modified harvest technique for cord blood hematopoietic stem cells. Bone Marrow Transplant 1992; 10: 89–91. Standardization of cord blood bank organization: (Coordinator, C Barucha). Panel discussion. Eurocord Transplant Workshop Meeting, Annecy, 1996. Rubinstein P, Carrier C, Scaradavou A et al. Outcomes among 562 recipients of placental blood transplants from unrelated donors. New Engl J Med 1998; 339: 1565–1577. O’Reilly R, Hansen JA, Kurzberg J et al. Allogeneic marrow transplants: approaches for the patient lacking a donor. Education Program. Thirty-eighth Annual Meeting of the American Society of Hematology, Orlando, 1996, pp 132–146.
while GVHD prophylaxis consisted of cyclosporin and methotrexate. Engraftment was associated with moderate progressive chronic GVHD, successfully managed with prednisone. On day ⫹106, the patient was readmitted with fever, hypotension and a single convulsive episode. CT scan of the brain demonstrated a hyperdense lesion in the left cerebral hemisphere, suggestive of intracranial hemorrhage secondary to cerebral infarction. Brain biopsy demonstrated extensive necrosis and non-specific hemorrhagic cerebritis. Amphotericin B therapy was begun because of bilateral interstitial and alveolar infiltrates on CT scan of the chest suggestive of pulmonary fungal infection. A second CT scan of the brain taken 30 days later revealed a single hypodense lesion with no peripheral contrast enhancement. On day ⫹148, he was still febrile and suffered two new convulsive episodes, despite adequate anticonvulsive therapy. There was a gradual deterioration of his condition and he died on day ⫹153. Post-morten histological examination revealed an extensive necrotic and hemorrhagic cerebral lesion with intracellular pseudocysts in the brain consistent with active toxoplasmosis. During
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the clinical course, the patient did not develop serum or CSF anti-toxoplasma IgM antibody, and IgG antibody titers remained unaltered on repeated testing. Toxoplasma gondii infection is endemic in much of Europe and developing countries. The estimated rate of seropositivity in Brazil varies from 54 to 75%,5 whereas in a study from Seattle it was 15%.6 Despite this, documented infection is rarely reported in BMT recipients and then most cases of active toxoplasma infection are believed to be reactivation of latent disease secondary to impaired cellular and humoral immunity.1 Although toxoplasmosis may be associated with multiorgan involvement, the brain is most frequently affected in immunocompromised hosts. It has been proposed that disruption of Toxoplasma cysts occurs continually in the brains of infected people, but toxoplasmic encephalitis develops only in the setting of impaired host immunity.7 Intracranial hemorrhage due to toxoplasmosis3 is uncommon even among AIDS patients, where cerebral toxoplasmosis is a major cause of morbidity and mortality. After BMT, intracerebral hemorrhage represents one of the most common causes of neurological complications,8 being related to fungal and viral infections, cerebral infarction following nonbacterial thrombotic endocarditis, or less likely to low platelet levels.8 To the best of our knowledge, this case represents only the second documented report6 of cerebral toxoplasmosis presenting with a single hemorrhagic lesion. Furthermore, Cancelas et al9 reported a similar case of a post-BMT patient who experienced convulsions with repeatedly negative CT scans and yet at post-mortem cerebral cysts were detected. Direct involvement of the vascular endothelium by parasites with mass cell destruction, or vasculitis with extensive vessel wall necrosis, with or without a bleeding disorder, provide a possible explanation for such events.3,4 Toxoplasmosis infection after BMT usually manifests between the 2nd and 6th month following BMT and is associated with a poor outcome. Only four of the 57 reported cases in the literature survived.1 Our patient underwent repeated serological tests and brain biopsy, confirming other reports that making an early diagnosis is extremely difficult.1 Therefore, as stated earlier by Cancelas et al,9 high sensitivity diagnostic methods, such as PCR amplification of specific Toxoplasma gondii genes or antigen detection should be combined with other diagnostic procedures10,11 (blood culture10 or CSF analysis11) in order to improve early detection of toxoplasma infection. CT images of brain abscesses on immunocompetent patients are characterized by abnormal enhancement associated with vasogenic edema, possibly related to a breakdown of the blood–brain barrier caused by the inflammatory response to the infection within the brain parenchyma.12 In bone marrow transplant recipients these findings are not always present,13 which appears to be related to a diminished or lack of immunologic/ inflammatory reaction to the organism. Furthermore, Enzmann et al14 found that immunosuppressed patients whose brain showed typical ring enhancement on CT scans, and consequently had a better immune status, have a better prognosis than patients with no typical contrast enhancement.
In summary, this case illustrates acute cerebral toxoplasmosis as a possible cause of infarction with intracranial hemorrhage post-BMT, producing typical hyperdense lesions on CT scans. Thus, clinicians should have a high level of suspicion of Toxoplasmosis in seropositive patients, not withholding the utilization of the more sensitive diagnostic tests, even when presentation and routine investigations are atypical, with a view to instituting early treatment. LF Bleggi-Torres1 BC de Medeiros1 B Werner1 R Pasquini2 CR de Medeiros2
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Department of Pathology and 2Bone Marrow Transplantation Unit, Hospital de Clı´nicas/UFPR, Rua General Carneiro 181, 80060-900, Curitiba, Brazil
References 1 Pendry K, Tait RC, McLay A et al. Toxoplasmosis after BMT for CML. Bone Marrow Transplant 1990; 5: 65–66. 2 Wolff D, Becker C, Kubel M et al. Second unrelated bone marrow transplantation without additional conditioning therapy after engraftment failure. Bone Marrow Transplant 1998; 21: 315–317. 3 Trenkwalder P, Trenkwalder C, Feiden W et al. Toxoplasmosis with early intracerebral hemorrhage in a patient with the acquired immunodeficiency syndrome. Neurology 1992; 42: 436–438. 4 Revel MP, Gray F, Brugieres P et al. Hyperdense CT foci in treated AIDS toxoplasmosis encephalitis: MR and pathologic correlation. J Comput Assist Tomogr 1992; 16: 372–375. 5 Ricciardi ID, Sabroza DC, Sandoval ED, Mayink W. Seroepidemiological study on the prevalence of human toxoplasmosis in Brazil. Ver Microbiol 1978; 9: 181–187. 6 Slavin MA, Meyers JD, Remington JS, Hackman RC. Toxoplasma gondii infection in marrow transplant recipients: a 20 year experience. Bone Marrow Transplant 1994; 13: 549–557. 7 Hunter CA, Remington JS. Immunopathogenesis of toxoplasmic encephalitis. J Infect Dis 1994; 170: 1057–1067. 8 Mohrmann RL, Mah V, Vinters HV. Neuropathologic findings after bone marrow transplantation: an autopsy study. Hum Pathol 1990; 21: 630–639. 9 Cancelas JA, Lopez-Jimenez J, Gonzalez C et al. Cerebral toxoplasmosis of atypical presentation in a bone marrow transplant patient. Med Clin (Barc) 1994; 103: 383–384. 10 Michel G, Thuret I, Chambost H et al. Lung toxoplasmosis after HLA-mismatched bone marrow transplantation. Bone Marrow Transplant 1994; 14: 455–457. 11 Brinkman K, Debast S, Sauerwein R et al. Toxoplasma retinitis/encephalitis 9 months after allogeneic bone marrow transplantation. Bone Marrow Tranplant 1998; 21: 635–636. 12 Greenwood J. Mechanisms of blood–brain barrier breakdown. Neuroradiology 1991; 33: 95–100. 13 Yuh WTC, Nguyen HD, Gao F et al. Brain parenchyma infection in bone marrow transplantation patients: CT and MRI findings. Am J Roentgenol 1994; 162: 425–430. 14 Enzmann DR, Brant-Zawadzki M, Britt RH. CT of central nervous system infections in immunocompromised patients. AJR 1980; 135: 263–267.
