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Biology of Blood and Marrow Transplantation 10:741-742 (2004)� 2004 American Society for Blood and Marrow Transplantation1083-8791/04/1011-0001$30.00/0doi:10.1016/j.bbmt.2004.07.003

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he Successful Treatment of Severe Aplastic Anemiaith Autologous Cord Blood Transplantation

Steven M. Fruchtman,1 Anne Hurlet,2 Robert Dracker,3 Luis Isola,1 Benjamin Goldman,2

Benjamin L. Schneider,2 Sukru Emre4

1Departments of Medicine and 2Pediatrics, Mount Sinai Medical Center, New York, New York; 3Viacell, Inc,Boston, Massachusetts; and 4Transplantation Institute, Mount Sinai Medical Center, New York, New York

Correspondence and reprint requests: Steven M. Fruchtman, MD, The Mount Sinai Hospital, One Gustave LevyPlace, 5 East 98th St, Box 1410, New York, NY 10029 (e-mail: Steven.Fruchtman@msnyuhealth.org).

Received June 9, 2004; accepted July 15, 2004

ABSTRACTCord blood transplantation has been used extensively in the allogeneic setting for acquired and geneticdisorders of hematopoiesis. There is less experience in the utility of autologous cord blood transplantation, andthere is great controversy about the role of autologous cord blood collection and storage. We report on thesuccessful use of autologous cord blood transplantation for the treatment of severe aplastic anemia followingfulminant hepatic failure and living related liver transplantation.© 2004 American Society for Blood and Marrow Transplantation

KEY WORDS

Anemia ● Aplastic ● Autologus ● Transplantation ● Cord blood

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We report the first case of autologous cord bloodransplantation for the treatment of severe aplasticnemia secondary to liver transplantation. A 20-onth-old boy presented with fulminant hepatic fail-

re of unknown etiology. Markers for viral hepatitisnd congenital causes of fulminant hepatic failureere negative. A living related liver transplantation

rom his haploidentical father was performed. Threeonths later, the patient developed pancytopenia

white blood cells �200/�L; platelets �7000/�L).one marrow was empty on biopsy. Etiology for se-ere aplastic anemia could not be determined. Heeceived increasing doses of cyclosporine and steroidsor immunomodulation. He remained neutropenic,as dependent on transfusions of red blood cells andlatelets, and had no HLA-matched siblings. The pa-ient’s parents, both physicians, had arranged for thetorage of the patient’s cord blood at birth. It wasecided to use the stored cord blood as an autologousord blood transplant in an attempt to restore normalematopoiesis. A Nunc vial stored with the cord bloodas thawed to confirm that it was HLA identical to theatient. The preparative regimen consisted of antithy-ocyte globulin 40 mg/kg/d, cyclosporine, and pred-

isone given for 4 days along with granulocyte colony-

timulating factor, followed by infusion of 7.98 � 107 b

B & M T

otal nucleated cells per kilogram containing 2.79 �05 CD34� cells per kilogram. White blood cell en-raftment (�1000/�L) occurred by day 11 and plate-et engraftment by day 14 (�20 000/�L). The pa-ient’s recovery was unremarkable, except for a skiniopsy positive for Aspergillus spp, which was treatedith antifungal agents. At 3 years of follow-up, theatient remains on immunosuppressive therapy for hismmunosuppressive regimen after living related liverransplantation and is in complete hematologic remis-ion with a normal complete blood count.

Severe aplastic anemia, a life-threatening he-atologic emergency requiring prompt treatment, has

een reported in certain settings to occur in up to8% of recipients of orthotopic liver transplants [1].arrow transplantation from an HLA-matched sib-

ing donor has high rates of cure in children withplastic anemia [2], but matched or compatible donorsre not always available. In the absence of a matchedonor, immunosuppressive therapy can restore hema-ologic function in some patients, but pancytopeniarequently recurs, and eventual transformation to my-lodysplastic syndrome and acute leukemia is a risk.

Cord blood has been used for more than a decades a source of stem cells for allogeneic transplantation,

ut reports of its use in children with aplastic anemia

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S. M. Fruchtman et al.

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econdary to liver transplantation are rare. In theon–liver transplant setting, 2 cases of hematopoieticransplantation with allogeneic cord blood and bonearrow from HLA-matched siblings have been re-

orted: one in a 7-year-old boy with acquired severeplastic anemia [3] and the other in a 9-year-old girlith myelodysplastic syndrome due to hepatitis-asso-

iated aplastic anemia [4]. In both cases, engraftmentas prompt (�1 month) and successful.

Three cases of severe aplastic anemia after ortho-opic liver transplantation have been reported (Table 1).n all cases, prompt hematopoietic recovery was success-ully achieved by using marrow from HLA-matchediblings [5-7]. Umeda et al. [8] described a case of a-year-old boy who developed aplastic anemia after aiving related liver transplantation from his HLA-hap-oidentical father (Table 1). The patient was plateletransfusion dependent and developed 2 episodes of life-hreatening intracranial hemorrhage while receiving im-unosuppressive therapy. Marrow engraftment was

chieved by using stem cell transplantation with relatedllogeneic cord blood and bone marrow from an HLA-atched sibling.

To our knowledge, our case is the first report ofhe successful treatment of severe aplastic anemia bysing only autologous cord blood. Of note, because Tells derived from the cord will develop in the settingf exposure to the HLA-disparate liver graft, there islso the possibility of inducing HLA-disparate toler-nce; thus, the recipient may not require chronic im-

able 1. Cases of Hematopoietic Transplantation in Children with Seve

Patient Liver Transplant Type

Hem

Source

.6-year-old boy Living–related, HLAhaploidentical father

Cord bloo

-year-old boy [8] Living–related, HLAhaploidentical father

Cord bloo

-year-old boy [5] Orthotopic Marrow.5-year-old boy [6] Orthotopic Marrow.5-year-old boy [7] Orthotopic Marrow

Indicates recovery defined as platelets � 20,000/mm3. In other cases,

unosuppression.

42

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. Dallorso S, Dufour C, Bertolini F, Dini G, Sirchia G, Mori PG.Combined transplantation with related HLA-identical cordblood and bone marrow in a child with severe aplastic anemia.Eur J Haematol. 1996;56:256-258.

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. Hagglund H, Winiarski J, Ringden O, et al. Successful alloge-neic bone marrow transplantation in a 2.5-year-old boy withongoing cytomegalovirus viremia and severe aplastic anemiaafter orthotopic liver transplantation for non-A, non-B, non-Chepatitis. Transplantation. 1997;64:1207-1208.

. Umeda K, Adachi S, Watanabe K, Kimura N, Lin Y, NakahataT. Successful hematopoietic stem cell transplantation for aplasticanemia following living-related liver transplantation. Bone Mar-

stic Anemia Post-Liver Transplantation

ietic Transplantation Time to Engraftment

Donor WBC Neutrophils Platelets*

Self 11 d 14d*

HLA-matched, ABOincompatible sister

12 d 45 d

HLA-matched brother 20 dHLA-matched sister 23 d 19d*HLA-matched sister,

Group A identical11 d 12 d

y defined as platelets � 50,000/mm3.

re Apla

atopo

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row Transplant. 2002;30:531-534.