Correspondence

Transmission of Chronic Myeloid Leukemia through Peripheral-Blood Stem-Cell Transplantation

N Engl J Med 2003; 349:913-914August 28, 2003

Article

To the Editor:

Although secondary cancer is a well-established long-term complication of hematopoietic stem-cell transplantation,1 the transmission of hematologic cancers through marrow or solid-organ transplantation is exceptional.2 Moreover, to our knowledge, it has not been reported after peripheral-blood stem-cell transplantation.

A nine-year-old African child received a diagnosis of sickle cell disease (hemoglobin SC) in 1991. Between 1991 and 2001, he had multiple vaso-occlusive crises, despite hydroxyurea therapy. He was referred to us at the age of 19 years for transplantation of peripheral-blood stem-cells from an HLA-identical brother who was heterozygous for sickle cell disease.3,4 Before peripheral-blood stem-cell mobilization with a six-day regimen of granulocyte colony-stimulating factor at a dose of 10 μg per kilogram of body weight, the donor's physical examination and hematologic studies were unremarkable, except for a slight inversion of the neutrophil:lymphocyte ratio, as is frequently observed in African persons (Table 1Table 1Hematologic Values in the Donor before and after Peripheral-Blood Stem-Cell Donation.).

After conditioning with oral busulfan (16 mg per kilogram), intravenous cyclophosphamide (200 mg per kilogram), and antithymocyte globulin (90 mg per kilogram), the patient received a CD34-selected peripheral-blood stem-cell graft containing 4×10⁶ CD34+ cells per kilogram and 0.01×10⁶ CD3+ cells per kilogram. Prophylaxis against graft-versus-host disease was carried out with cyclosporine alone. The immediate post-transplantation course was complicated by cyclosporine-associated pancreatitis that resolved after the withdrawal of cyclosporine on day 21, and the patient was discharged on day 35. Neither acute nor chronic graft-versus-host disease developed.

The results of bone marrow evaluation on day 100 were normal, with more than 95 percent chimerism, but the karyotype showed a Philadelphia chromosome in 9 of 31 metaphases. Fluorescence in situ hybridization analysis confirmed the BCR-ABL rearrangement in 14 percent of marrow cells. Bone marrow evaluation in the donor showed chronic-phase chronic myeloid leukemia with the Philadelphia chromosome in 95 percent of the cells. The recipient was treated with STI571, and a complete cytogenetic and molecular remission was achieved three and six months later, respectively. Now, more than one year after the transplantation, the patient is well, without any sign of chronic graft-versus-host disease, and is heterozygous for sickle cell disease (the status of the donor). The donor initially received interferon alfa but did not tolerate it and then received STI571; a complete cytogenetic response was achieved, but a complete molecular response has not yet occurred.

Transmission of acute myeloid leukemia as well as T-cell lymphoma through bone marrow transplantation has been reported previously.2,5 However, this case shows that chronic myeloid leukemia can also be transmitted through transplantation of peripheral-blood stem cells from a donor with no sign of chronic myeloid leukemia in the peripheral blood. This raises the issue of routine bone marrow and karyotype examination in donors of peripheral-blood stem cells.4 However dramatic such cases are, it would be costly and ineffective, as well as uncomfortable for the donor, to carry out these investigations systematically in all donors.

Frederic Baron, M.D., Ph.D.
Marie-Françoise Dresse, M.D.
Yves Beguin, M.D., Ph.D.
University of Liège, 4000 Liège, Belgium
yves.beguin@chu.ulg.ac.be

5 References

1. 1

   Curtis RE, Rowlings PA, Deeg HJ, et al. Solid cancers after bone marrow transplantation. N Engl J Med 1997;336:897-904
   Full Text | Web of Science | Medline

2. 2

   Niederwieser DW, Appelbaum FR, Gastl G, et al. Inadvertent transmission of a donor's acute myeloid leukemia in bone marrow transplantation for chronic myelocytic leukemia. N Engl J Med 1990;322:1794-1796
   Full Text | Web of Science | Medline

3. 3

   Walters MC, Patience M, Leisenring W, et al. Bone marrow transplantation for sickle cell disease. N Engl J Med 1996;335:369-376
   Full Text | Web of Science | Medline

4. 4

   Vermylen C, Cornu G, Ferster A, et al. Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium. Bone Marrow Transplant 1998;22:1-6
   CrossRef | Web of Science | Medline

5. 5

   Berg KD, Brinster NK, Huhn KM, et al. Transmission of a T-cell lymphoma by allogeneic bone marrow transplantation. N Engl J Med 2001;345:1458-1463
   Full Text | Web of Science | Medline

Citing Articles (12)

Citing Articles

1. 1

   Daniel H. Wiseman. (2011) Donor Cell Leukemia: A Review. Biology of Blood and Marrow Transplantation 17:6, 771-789
   CrossRef

2. 2

   Sergey V. Anisimov, Asuka Morizane, Ana S. Correia. (2010) Risks and Mechanisms of Oncological Disease Following Stem Cell Transplantation. Stem Cell Reviews and Reports 6:3, 411-424
   CrossRef

3. 3

   Hung Yang, June Lee, Clive R. Seed, Anthony J. Keller. (2010) Can Blood Tranfusion Transmit Cancer? A Literature Review. Transfusion Medicine Reviews 24:3, 235-243
   CrossRef

4. 4

   Lewis Glasser, Aurelia Meloni-Ehrig, Wesley Greaves, Kurt C. Demel, James Butera. (2009) Synchronous development of acute myeloid leukemia in recipient and donor after allogeneic bone marrow transplantation: report of a case with comments on donor evaluation. Transfusion 49:3, 555-562
   CrossRef

5. 5

   Noelle V. Frey, Christopher E. Leid, Peter C. Nowell, Ewa Tomczak, Honore T. Strauser, Margaret Kasner, Steven Goldstein, Alison Loren, Edward Stadtmauer, Selina Luger, Elizabeth Hexner, Joanne Hinkle, David L. Porter. (2008) Trisomy 8 in an allogeneic stem cell transplant recipient representative of a donor-derived constitutional abnormality. American Journal of Hematology 83:11, 846-849
   CrossRef

6. 6

   A Kolstad, G Tjønnfjord, V Jønsson. (2008) High frequency of unrecognized indolent hematological disorders among HLA-matched siblings of patients with lymphoproliferative malignancies eligible for allo-SCT. Bone Marrow Transplantation 42:6, 427-428
   CrossRef

7. 7

   Manish J. Gandhi, D. Michael Strong. (2007) Donor derived malignancy following transplantation: a review. Cell and Tissue Banking 8:4, 267-286
   CrossRef

8. 8

   F Baron, B M Sandmaier. (2006) Chimerism and outcomes after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. Leukemia 20:10, 1690-1700
   CrossRef

9. 9

   Julian Sevilla, Sergio Querol, Antonio Molines, Marta Gonzalez-Vicent, Antonio Balas, Ana Carrio, Jesus Estella, Miguel Angel Diaz, Luis Madero. (2006) Transient donor cell-derived myelodysplastic syndrome with monosomy 7 after unrelated cord blood transplantation. European Journal of Haematology 77:3, 259-263
   CrossRef

10. 10

    Olga Sala-Torra, Colleen Hanna, Michael R. Loken, Mary E.D. Flowers, Michael Maris, Paula A. Ladne, James R. Mason, David Senitzer, Roberto Rodriguez, Stephen J. Forman, H. Joachim Deeg, Jerald P. Radich. (2006) Evidence of Donor-Derived Hematologic Malignancies after Hematopoietic Stem Cell Transplantation. Biology of Blood and Marrow Transplantation 12:5, 511-517
    CrossRef

11. 11

    Hideki Mitsui, Norimitsu Saito, Atsushi Satake, Tsuyoshi Nakazawa, Takahiro Karasuno, Akira Hiraoka. (2005) A Novel Chromosomal Abnormality, t(6;10)(q27;q22), Found in a Polycythemic Potential Donor for Allogeneic Hematopoietic Stem Cell Transplantation. International Journal of Hematology 82:1, 72-74
    CrossRef

12. 12

    H. B. Pralle, C. Weber. (2005) Hmatologische Neoplasien und Schwangerschaft. Der Gynkologe 38:2, 119-126
    CrossRef