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1. Cord blood donor cell leukemia in recipients. Greaves MF. Leukemia. 2006; 20:1633-4.

The authors comment on a report by Ando et al (Donor cell-derived acute myeloid leukemia after unrelated umbilical cord blood transplantation. Ando T et al. Leukemia. 2006; 20:744-5) which describes a case of AML of donor cell origin following cord blood transplantation. They state that other cases have been observed including two cases not yet published. Although a similar phenomenon has been recorded in more than 20 cases following conventional BMT, the authors speculate that this event may be substantially more frequent with a cord blood source of stem cells. The authors discuss the possibility of testing of cord bloods for pre-leukemic clones. They point out that, although this might be desirable, it would not be very practical given the wide variety of chromosomal and mutational events that could initiate acute leukemia. Cord blood has been a very considerable success and it is unlikely that donor cell leukemia would seriously compromise its continued use. Nevertheless, there is not some urgency to establish the frequency of donor cell leukemia by more systematic screening of “relapse” cases and identifying whether or not this reflects transfer of pre-leukemic clones.

(NOTE: For further information about donor-cell leukemia following cord blood transplantation, see the citations below AND Annotated Bibliography XXIII. ASH Meeting December 2006, xii. Adverse events.)

2. First report of donor cell derived acute leukemia as a complication of umbilical cord blood transplantation. Christopher J Fraser, Betsy A Hirsch, Vanessa Dayton, Michael H Creer, Joseph P Neglia, John E Wagner, and K S Baker. Blood 2005:106:4377-4380.

The authors indicate that more than 6000 cord blood transplants have been performed worldwide and donor cell derived leukemia has not previously been reported, although there are approximately 25 such reports following hematopoietic cell transplantation.

A twelve month old boy underwent unrelated donor umbilical cord blood transplant (UCBT) for refractory Langerhan's cell histiocytosis. Forty months following transplant he developed acute myeloid leukemia. Cytogenetic and molecular analysis confirmed donor cell origin. The Cord Blood Bank (CBB) contacted the donor's family and established that the child, now seven years old, was healthy.

The identification of clonotypic gene fusion sequences in the neonatal blood spots of children who subsequently developed leukemias suggests that transmission of leukemic or pre-leukemic cells from a neonatal donor could occur. It has already been suggested that such data argue against the use of stored cord blood in an autologous setting for leukemia patients. In the present case no stored sample of the cord blood unit was available to test for the presence of the cytogenetic clone. A decision was made not to request a blood sample from the donor because of a desire not to create undue anxiety and the absence of any prophylactic treatment or validated screening strategy.

3. Development of leukemia in donor cells after allogeneic stem cell transplantation--a survey of the European Group for Blood and Marrow Transplantation (EBMT). Hertenstein B, Hambach L, Bacigalupo A, Schmitz N, McCann S, Slavin S, Gratwohl A, Ferrant A, Elmaagacli A, Schwertfeger R, Locasciulli A, Zander A, Bornhauser M, Niederwieser D, Ruutu T; Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2005;90:969-75.

The authors indicate that leukemia in donor cells (donor cell leukemia; DCL) has been reported as a rare but severe complication of allogeneic stem cell transplantation (SCT). A questionnaire survey was carried out within European Blood and Marrow Transplantation Group (EBMT) centers. Ninety-one EBMT centers participated in this survey, covering 10489 allogeneic SCT between 12/1982 and 09/2003.

Fourteen cases of DCL, most with a myeloid phenotype (7 cases of acute myeloid leukemia, 3 each of acute lymphocytic leukemia and 1 case of chronic myeloid leukemia) were identified. Demonstration of donor cell origin included molecular analysis of chimerism in most cases. DCL type and cytogenetic alterations were independent from the original disease. The median time between transplantation and diagnosis of DCL was 17 months (4-164). No type of conditioning, donor, graft manipulation, graft-versus-host disease prophylaxis or subsequent complications were identified as risk factors for DCL. Chemotherapy induced remissions in DCL and 2 of 5 patients remain alive in remission after a second transplant. None of the stem cell donors developed hematologic malignancies (median follow-up period of 9 years; range 6-30 years).

The authors concluded that DCL is an extremely rare complication of allogeneic SCT in which treatment attempts with chemotherapy and a second SCT are justified. Donors are not at an increased risk of developing hematologic malignancies.

4. Donor cell derived acute myeloid leukemia after allogeneic cord blood transplantation in a patient with adult T-cell lymphoma. Matsunaga T, Murase K, Yoshida M, Fujimi A, Iyama S, Kuribayashi K, Sato T, Kogawa K, Hirayama Y, Sakamaki S, Kohda K, Niitsu Y. Am J Hematol. 2005;79:294-8.

The authors report a patient with adult T-cell lymphoma who developed acute myeloid leukemia (AML) after allogeneic cord blood transplantation (CBT). Fluorescence in situ hybridization (FISH) studies and molecular analysis using short tandem repeat (STR) sequences proved the AML to be of donor origin. Although 25 cases of donor cell leukemia (DCL) occurring after allogeneic bone marrow transplantation have previously been reported, the authors considered that this case is the first-reported DCL patient after CBT.