short report
Donor-derived myelodysplastic syndrome and acute leukaemia after allogeneic haematopoietic stem cell transplantation: incidence, natural history and treatment response
Andrew C. Dietz,1 Todd E. DeFor,2 Claudio G. Brunstein2,3 and John E. Wagner Jr2,4 1
Division of Hematology Oncology, and Blood
and Marrow Transplant, Department of Pediatrics, Rady Children’s Hospital, University of California San Diego, San Diego, CA, 2Blood and Marrow Transplant Program, University of Minnesota, 3Department of Medicine, University of Minnesota, and 4Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
Summary Donor-derived myelodysplastic syndrome/acute leukaemia (DD-MDS/AL) is a rare life-threatening complication of allogeneic haematopoietic stem cell (HSC) transplantation. However, it is unknown whether the risk differs by HSC source. Therefore, we evaluated the incidence of DD-MDS/AL in 2390 engrafted patients. With a median follow-up of 71 years (1–208), the incidence of DD-MDS/AL was 053% (95% confidence interval (CI), 001–141%], 056% (95%CI, 001–136%) and 056% (95%CI, 001–110%) in recipients of bone marrow (n = 1117), peripheral blood (n = 489) and umbilical cord blood (UCB, n = 784), respectively. While follow-up is shorter in recipients of UCB and peripheral blood, incidence of DD-MDS/AL is, thus far, similar between HSC sources.
Received 17 January 2014; accepted for publication 17 February 2014
Keywords: donor-derived leukaemia, haematopoietic cell transplantation.
Correspondence: John E. Wagner, Jr., MD, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA. E-mail [email protected]
Donor-derived myelodysplastic syndrome and acute leukaemia (DD-MDS/AL) are rare adverse events after allogeneic haematopoietic stem cell (HSC) transplantation. Originally identified in 1971 (Fialkow et al, 1971), nearly 90 cases have now been reported in the literature (Hertenstein et al, 2005; Ruiz-Arg€ uelles et al, 2007; Wang et al, 2011; Wiseman, 2011; Fraser et al, 2005; Matsunaga et al, 2005; Sevilla et al, 2006; Yamazaki et al, 2011; Gustafsson et al, 2011; Rodriquez-Macias et al, 2013; Nakamizo et al, 2011). Based on several reviews, the incidence of DD-MDS/AL has been estimated to be between 012% and 5% (Hertenstein et al, 2005; Ruiz-Arg€ uelles et al, 2007; Wang et al, 2011; Wiseman, 2011). While speculative in most cases, proposed mechanisms for the development of DD-MDS/AL include transplantation of donor haematopoietic progenitors with a cryptic translocation or a preleukaemic clone, presence of an underlying stromal defect either inherent in the host or acquired by preceding chemoradiotherapy, transformation of donor cells by viral or host antigenic stimulation, impaired immune surveillance, oncogene transfection by fusion of donor cells with residual leukaemic cells, prolonged use of granulocyte-colony stimulating factor (G-CSF, NEUPOGEN; Amgen, Thousand Oaks, CA, USA) and replicative stress during the period of marked HSC expansion after ª 2014 John Wiley & Sons Ltd, British Journal of Haematology
transplantation, or the presence of occult leukaemia in the donor (Hertenstein et al, 2005; Ruiz-Arg€ uelles et al, 2007; Wang et al, 2011; Wiseman, 2011). Since the first documented cases in 2005, reports of DD-MDS/DD-AL after umbilical cord blood (UCB) transplantation have been more frequent than with other HSC sources (Fraser et al, 2005; Matsunaga et al, 2005; Sevilla et al, 2006; Yamazaki et al, 2011; Gustafsson et al, 2011; RodriquezMacias et al, 2013; Nakamizo et al, 2011), causing some investigators to speculate that the incidence of DD-MDS/AL may be higher after UCB relative to bone marrow or mobilized peripheral blood transplantation (Greaves, 2006; Greaves et al, 2011). Greaves et al (2011) raised the important concern that UCB might carry an increased risk of DD-MDS/AL due to the presence of these pre-leukaemic clones previously shown to exist in a proportion of UCB samples (Greaves, 2006; Greaves et al, 2011). Because of the proliferative stress that invariably occurs after transplantation, it was hypothesized that a ‘second hit’ could enhance the risk of DD-MDS/DD-AL in cells already predisposed to leukaemogenesis. Therefore, we sought to determine the relative incidence of DD-MDS/AL between the three HSC sources in patients transplanted at the University of Minnesota after 1992, when molecular methods for evaluating chimerism were routine. In doi:10.1111/bjh.12847
Short Report Table I. Donor-derived myelodysplastic syndrome and acute leukaemia case characteristics. Age* (years)
CMV reactivation
Neutrophil recovery
056
Yes
Poor
42
AML
uUCB uUCB
042 020
Yes No
Good Good
19 3
MDS MDS
2007 1992
uUCB MSD BM
033 20
Yes No
Poor Good
1 180
MDS ALL
2000 1996 1998
MSD BM MSD PB MSD PB
No Yes No
Poor Good Poor
16 41 60
AML MDS AML
Primary diagnosis
Year of HSCT
Donor source
LCH
2000
uUCB
11 38
AML AML
2005 2005
57 6
MDS/AML AML
11 34† 47
FA CLL/tMDS MDS
1†
Cell dose (9108/kg)
10 72 195
Months to event
Event type
Treatment Chemo & 2nd Transplant 2nd Transplant Withdrawal of G-CSF Decitabine COG Protocol 1961 None Chemotherapy 2nd Transplant & DLI
Outcome (days after event) Dead (302) Dead (172) Alive at 6 years Dead (712) Alive at 6 years Dead (545) Dead (87) Dead (1537)
HSCT, haematopoietic stem cell transplantation; CMV, cytomegalovirus; LCH, Langerhans cell histiocytosis; AML, acute myeloid leukaemia; MDS, myelodysplastic syndrome; FA, Fanconi anaemia; CLL, chronic lymphocytic leukaemia; tMDS, therapy-related MDS; uUCB, unrelated umbilical cord blood; MSD, matched sibling donor; BM, bone marrow; PB, peripheral blood; Chemo, chemotherapy; G-CSF, granulocyte colonystimulating factor; COG, Children’s Oncology Group; DLI, donor lymphocyte infusion. *Age at initial diagnosis. †Previously reported cases.
addition, we describe the characteristics and outcomes in eight patients with proven DD-MDS/AL.
Methods A total of 2582 consecutive recipients of allogeneic HSC transplanted between January 1992 and December 2010 were identified (time points after 1 January, 2011 were excluded due to insufficient follow up). Patients with graft failure (n = 106) or who died prior to engraftment (n = 86) were excluded. For the 2390 evaluable patients, the donor was related (total n = 996; 502 marrow, 461 peripheral blood, 23 UCB and 10 mixed UCB and marrow) or unrelated (total n = 1394; 615 marrow, 19 peripheral blood and 760 UCB). The median follow up was 99 years [95% confidence interval (CI), 90–103], 63 years (95%CI, 59–73) and 55 years (95%CI, 51–60) for marrow, peripheral blood and UCB recipients, respectively (P < 001). Recipients of allogeneic HSC had marrow and/or peripheral blood examined for chimerism routinely at 1, 3, 6, 12 and 24 months after transplant and at the time of relapse when possible, and always when there was a change in the morphological and cytogenetic characteristics or phenotypic profile from the original diagnostic specimen. Chimerism was assessed by molecular methods as previously described (Fraser et al, 2005), using quantitative polymerase chain reaction (PCR) of informative polymorphic variable number tandem repeat or short tandem repeat regions in the recipient and donor on whole marrow or peripheral blood. Cases of DD-MDS/AL were confirmed by chimerism analysis. Charts of all identified cases were reviewed for details of natural history and treatment response. Cumulative 2
Fig 1. Incidence of donor-derived myelodysplastic syndrome and acute leukaemia by haematopoietic stem cell source. Incidence of donor-derived myelodysplastic syndrome and acute leukaemia was determined in 2390 engrafted patients transplanted either with bone marrow (BM, n = 1117), peripheral blood stem cells (PBSC, n = 489) or umbilical cord blood (UCB, n = 784).
incidence curves were created, treating non DD-MDS/AL death as a competing risk. Median follow-up by reverse censoring was 71 years (95%CI, 65–76). Statistics were performed using SAS 9.2 (SAS Institute Inc., Cary, ND, USA) with the dataset closed on 10 May, 2013. P-values 5 years in all groups, which is probably the
References Fialkow, P.J., Thomas, E.D., Bryant, J.I. & Neiman, P.E. (1971) Leukaemic transformation of engrafted human marrow cells in vivo. Lancet, 1, 251–255. Fraser, C.J., Hirsch, B.A., Dayton, V., Creer, M.H., Neglia, J.P., Wagner, J.E. & Baker, K.S. (2005) First report of donor cell-derived acute leukemia as a complication of umbilical cord blood transplantation. Blood, 106, 4377–4380. Greaves, M.F. (2006) Cord blood donor cell leukemia in recipients. Leukemia, 20, 1633– 1634.
highest risk period for the majority of patients based on this and other reports (Hertenstein et al, 2005; Ruiz-Arg€ uelles et al, 2007; Wang et al, 2011; Wiseman, 2011; Fraser et al, 2005; Matsunaga et al, 2005; Sevilla et al, 2006; Yamazaki et al, 2011; Gustafsson et al, 2011; Rodriquez-Macias et al, 2013; Nakamizo et al, 2011). Even if the follow-up period is restricted to an earlier time point, the incidence of DD-MDS/ AL after bone marrow transplant [010% (95%CI, 0–030%)] is not sufficiently different from that observed in recipients of peripheral blood or UCB transplant [056% (95%CI, 0–136%) and 056% (95%CI, 0–110%)] to reach statistical significance (P = 016). Importantly, abnormalities in chromosome 7 appear to be a common cytogenetic finding and some patients are curable simply by haematopoietic growth factor withdrawal, consistent with observations reported by others (Socie et al, 1999). In conclusion, these results provide a measure of reassurance that the incidence of DD-MDS/AL is low (1% or less) regardless of HSC source. However, longer follow up, particularly in recipients of UCB and peripheral blood, may be needed before making a definitive conclusion on the relative risks of DD-MDS/AL between the three HSC sources.
Support Supported by a Public Health Service grant P01-CA6549376518 (TED, CBG, JEWJ) from the National Cancer Institute, and the Children’s Cancer Research Fund (ACD, JEWJ).
Contributors ACD, TED, CGB and JEWJ contributed equally to study design, interpretation of data and drafting the manuscript. TED performed the statistical analysis. ACD, TED, JEWJ prepared the data file. ACD, TED, CGB, and JEWJ contributed to interpretation of data and critically reviewed the manuscript. All authors approved the final manuscript.
Conflict of interest The authors declare no conflicts of interest.
Greaves, M., Colman, S.M., Kearney, L. & Ford, A.M. (2011) Fusion genes in cord blood. Blood, 117, 369–370, author reply 370–361. Gustafsson, B., Moell, J., Leblanc, K., Barbany, G., S€ oderh€all, S. & Winiarski, J. (2011) Donor cellderived acute myeloid leukemia after second allogenic cord blood transplantation in a patient with Fanconi anemia. Pediatric Transplantation, 16, E241–E245. Hertenstein, B., Hambach, L., Bacigalupo, A., Schmitz, N., McCann, S., Slavin, S., Gratwohl, A., Ferrant, A., Elmaagacli, A., Schwertfeger, R., Locasciulli, A., Zander, A., Bornh€auser, M., Niederwieser, D., Ruutu, T., & Chronic Leukaemia
ª 2014 John Wiley & Sons Ltd, British Journal of Haematology
Working Party of the European Group for Blood and Marrow Transplantation (2005) Development of leukemia in donor cells after allogeneic stem cell transplantation–a survey of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica, 90, 969–975. Matsunaga, T., Murase, K., Yoshida, M., Fujimi, A., Iyama, S., Kuribayashi, K., Sato, T., Kogawa, K., Hirayama, Y., Sakamaki, S., Kohda, K. & Niitsu, Y. (2005) Donor cell derived acute myeloid leukemia after allogeneic cord blood transplantation in a patient with adult T-cell lymphoma. American Journal of Hematology, 9, 294–298.
3
Short Report Nakamizo, A., Akagi, Y., Amano, T., Suzuki, S.O., Otsuka, R., Abe, Y., Yoshimoto, K., Iwaki, T. & Sasaki, T. (2011) Donor-derived adult T-cell leukaemia. Lancet, 377, 1124. Rodriquez-Macias, G., Martinez-Laperche, C., Gayoso, J., Noriega, V., Serrano, D., Balsalobre, P., Munoz-Martinez, C., Diez-Martin, J.L. & Buno, I. (2013) Mutation of the NPM1 gene contributes to the development of donor-derived acute myeloid leukemia after unrelated cord blood transplantation for acute lymphoblastic leukemia. Human Pathology, 44, 1696–1699. Ruiz-Arg€ uelles, G.J., Ruiz-Arg€ uelles, A. & GarcesEisele, J. (2007) Donor cell leukemia: a critical review. Leukemia & Lymphoma, 48, 25–38. Sevilla, J., Querol, S., Molines, A., Gonzalez-Vicent, M., Balas, A., Carrio, A., Estella, J., Angel Diaz, M.
4
& Madero, L. (2006) Transient donor cell-derived myelodysplastic syndrome with monosomy 7 after unrelated cord blood transplantation. European Journal of Haematology, 77, 259–263. Socie, G., Stone, J.V., Wingard, J.R., Weisdorf, D., Henslee-Downey, P.J., Bredeson, C., Cahn, J.Y., Passweq, J.R., Rowlings, P.A., Schouten, H.C., Kolb, H.J. & Klein, J.P. (1999) Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. New England Journal of Medicine, 341, 14–21. Wang, E., Hutchinson, C.B., Huang, Q., Lu, C.M., Crow, J., Wang, F.F., Sebastian, S., Rehder, C., Lagoo, A., Horwitz, M., Rizzieri, D., Yu, J., Goodman, B., Datto, M. & Buckley, P. (2011)
Donor cell-derived leukemias/myelodysplastic neoplasms in allogeneic hematopoietic stem cell transplant recipients: a clinicopathologic study of 10 cases and a comprehensive review of the literature. American Journal of Clinical Pathology, 135, 525–540. Wiseman, D.H. (2011) Donor cell leukemia: a review. Biology of Blood and Marrow Transplantation, 17, 771–789. Yamazaki, R., Nakasone, H., Wada, H., Sakamoto, K., Ashizawa, M., Sato, M., Terasako, K., Kikuchi, M., Kimura, S., Okuda, S., Kako, S., Tanaka, Y., Tanihara, A. & Oshima, K. (2011) Recurrence of monoclonal gammopathy associated with donor-derived myelodysplastic syndrome after cord blood stem cell transplantation. Experimental Hematology, 39, 1119–1123.
ª 2014 John Wiley & Sons Ltd, British Journal of Haematology
Donor-derived myelodysplastic syndrome and acute leukaemia after allogeneic haematopoietic stem cell transplantation: incidence, natural history and treatment response
Andrew C. Dietz,1 Todd E. DeFor,2 Claudio G. Brunstein2,3 and John E. Wagner Jr2,4 1
Division of Hematology Oncology, and Blood
and Marrow Transplant, Department of Pediatrics, Rady Children’s Hospital, University of California San Diego, San Diego, CA, 2Blood and Marrow Transplant Program, University of Minnesota, 3Department of Medicine, University of Minnesota, and 4Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
Summary Donor-derived myelodysplastic syndrome/acute leukaemia (DD-MDS/AL) is a rare life-threatening complication of allogeneic haematopoietic stem cell (HSC) transplantation. However, it is unknown whether the risk differs by HSC source. Therefore, we evaluated the incidence of DD-MDS/AL in 2390 engrafted patients. With a median follow-up of 71 years (1–208), the incidence of DD-MDS/AL was 053% (95% confidence interval (CI), 001–141%], 056% (95%CI, 001–136%) and 056% (95%CI, 001–110%) in recipients of bone marrow (n = 1117), peripheral blood (n = 489) and umbilical cord blood (UCB, n = 784), respectively. While follow-up is shorter in recipients of UCB and peripheral blood, incidence of DD-MDS/AL is, thus far, similar between HSC sources.
Received 17 January 2014; accepted for publication 17 February 2014
Keywords: donor-derived leukaemia, haematopoietic cell transplantation.
Correspondence: John E. Wagner, Jr., MD, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA. E-mail [email protected]
Donor-derived myelodysplastic syndrome and acute leukaemia (DD-MDS/AL) are rare adverse events after allogeneic haematopoietic stem cell (HSC) transplantation. Originally identified in 1971 (Fialkow et al, 1971), nearly 90 cases have now been reported in the literature (Hertenstein et al, 2005; Ruiz-Arg€ uelles et al, 2007; Wang et al, 2011; Wiseman, 2011; Fraser et al, 2005; Matsunaga et al, 2005; Sevilla et al, 2006; Yamazaki et al, 2011; Gustafsson et al, 2011; Rodriquez-Macias et al, 2013; Nakamizo et al, 2011). Based on several reviews, the incidence of DD-MDS/AL has been estimated to be between 012% and 5% (Hertenstein et al, 2005; Ruiz-Arg€ uelles et al, 2007; Wang et al, 2011; Wiseman, 2011). While speculative in most cases, proposed mechanisms for the development of DD-MDS/AL include transplantation of donor haematopoietic progenitors with a cryptic translocation or a preleukaemic clone, presence of an underlying stromal defect either inherent in the host or acquired by preceding chemoradiotherapy, transformation of donor cells by viral or host antigenic stimulation, impaired immune surveillance, oncogene transfection by fusion of donor cells with residual leukaemic cells, prolonged use of granulocyte-colony stimulating factor (G-CSF, NEUPOGEN; Amgen, Thousand Oaks, CA, USA) and replicative stress during the period of marked HSC expansion after ª 2014 John Wiley & Sons Ltd, British Journal of Haematology
transplantation, or the presence of occult leukaemia in the donor (Hertenstein et al, 2005; Ruiz-Arg€ uelles et al, 2007; Wang et al, 2011; Wiseman, 2011). Since the first documented cases in 2005, reports of DD-MDS/DD-AL after umbilical cord blood (UCB) transplantation have been more frequent than with other HSC sources (Fraser et al, 2005; Matsunaga et al, 2005; Sevilla et al, 2006; Yamazaki et al, 2011; Gustafsson et al, 2011; RodriquezMacias et al, 2013; Nakamizo et al, 2011), causing some investigators to speculate that the incidence of DD-MDS/AL may be higher after UCB relative to bone marrow or mobilized peripheral blood transplantation (Greaves, 2006; Greaves et al, 2011). Greaves et al (2011) raised the important concern that UCB might carry an increased risk of DD-MDS/AL due to the presence of these pre-leukaemic clones previously shown to exist in a proportion of UCB samples (Greaves, 2006; Greaves et al, 2011). Because of the proliferative stress that invariably occurs after transplantation, it was hypothesized that a ‘second hit’ could enhance the risk of DD-MDS/DD-AL in cells already predisposed to leukaemogenesis. Therefore, we sought to determine the relative incidence of DD-MDS/AL between the three HSC sources in patients transplanted at the University of Minnesota after 1992, when molecular methods for evaluating chimerism were routine. In doi:10.1111/bjh.12847
Short Report Table I. Donor-derived myelodysplastic syndrome and acute leukaemia case characteristics. Age* (years)
CMV reactivation
Neutrophil recovery
056
Yes
Poor
42
AML
uUCB uUCB
042 020
Yes No
Good Good
19 3
MDS MDS
2007 1992
uUCB MSD BM
033 20
Yes No
Poor Good
1 180
MDS ALL
2000 1996 1998
MSD BM MSD PB MSD PB
No Yes No
Poor Good Poor
16 41 60
AML MDS AML
Primary diagnosis
Year of HSCT
Donor source
LCH
2000
uUCB
11 38
AML AML
2005 2005
57 6
MDS/AML AML
11 34† 47
FA CLL/tMDS MDS
1†
Cell dose (9108/kg)
10 72 195
Months to event
Event type
Treatment Chemo & 2nd Transplant 2nd Transplant Withdrawal of G-CSF Decitabine COG Protocol 1961 None Chemotherapy 2nd Transplant & DLI
Outcome (days after event) Dead (302) Dead (172) Alive at 6 years Dead (712) Alive at 6 years Dead (545) Dead (87) Dead (1537)
HSCT, haematopoietic stem cell transplantation; CMV, cytomegalovirus; LCH, Langerhans cell histiocytosis; AML, acute myeloid leukaemia; MDS, myelodysplastic syndrome; FA, Fanconi anaemia; CLL, chronic lymphocytic leukaemia; tMDS, therapy-related MDS; uUCB, unrelated umbilical cord blood; MSD, matched sibling donor; BM, bone marrow; PB, peripheral blood; Chemo, chemotherapy; G-CSF, granulocyte colonystimulating factor; COG, Children’s Oncology Group; DLI, donor lymphocyte infusion. *Age at initial diagnosis. †Previously reported cases.
addition, we describe the characteristics and outcomes in eight patients with proven DD-MDS/AL.
Methods A total of 2582 consecutive recipients of allogeneic HSC transplanted between January 1992 and December 2010 were identified (time points after 1 January, 2011 were excluded due to insufficient follow up). Patients with graft failure (n = 106) or who died prior to engraftment (n = 86) were excluded. For the 2390 evaluable patients, the donor was related (total n = 996; 502 marrow, 461 peripheral blood, 23 UCB and 10 mixed UCB and marrow) or unrelated (total n = 1394; 615 marrow, 19 peripheral blood and 760 UCB). The median follow up was 99 years [95% confidence interval (CI), 90–103], 63 years (95%CI, 59–73) and 55 years (95%CI, 51–60) for marrow, peripheral blood and UCB recipients, respectively (P < 001). Recipients of allogeneic HSC had marrow and/or peripheral blood examined for chimerism routinely at 1, 3, 6, 12 and 24 months after transplant and at the time of relapse when possible, and always when there was a change in the morphological and cytogenetic characteristics or phenotypic profile from the original diagnostic specimen. Chimerism was assessed by molecular methods as previously described (Fraser et al, 2005), using quantitative polymerase chain reaction (PCR) of informative polymorphic variable number tandem repeat or short tandem repeat regions in the recipient and donor on whole marrow or peripheral blood. Cases of DD-MDS/AL were confirmed by chimerism analysis. Charts of all identified cases were reviewed for details of natural history and treatment response. Cumulative 2
Fig 1. Incidence of donor-derived myelodysplastic syndrome and acute leukaemia by haematopoietic stem cell source. Incidence of donor-derived myelodysplastic syndrome and acute leukaemia was determined in 2390 engrafted patients transplanted either with bone marrow (BM, n = 1117), peripheral blood stem cells (PBSC, n = 489) or umbilical cord blood (UCB, n = 784).
incidence curves were created, treating non DD-MDS/AL death as a competing risk. Median follow-up by reverse censoring was 71 years (95%CI, 65–76). Statistics were performed using SAS 9.2 (SAS Institute Inc., Cary, ND, USA) with the dataset closed on 10 May, 2013. P-values 5 years in all groups, which is probably the
References Fialkow, P.J., Thomas, E.D., Bryant, J.I. & Neiman, P.E. (1971) Leukaemic transformation of engrafted human marrow cells in vivo. Lancet, 1, 251–255. Fraser, C.J., Hirsch, B.A., Dayton, V., Creer, M.H., Neglia, J.P., Wagner, J.E. & Baker, K.S. (2005) First report of donor cell-derived acute leukemia as a complication of umbilical cord blood transplantation. Blood, 106, 4377–4380. Greaves, M.F. (2006) Cord blood donor cell leukemia in recipients. Leukemia, 20, 1633– 1634.
highest risk period for the majority of patients based on this and other reports (Hertenstein et al, 2005; Ruiz-Arg€ uelles et al, 2007; Wang et al, 2011; Wiseman, 2011; Fraser et al, 2005; Matsunaga et al, 2005; Sevilla et al, 2006; Yamazaki et al, 2011; Gustafsson et al, 2011; Rodriquez-Macias et al, 2013; Nakamizo et al, 2011). Even if the follow-up period is restricted to an earlier time point, the incidence of DD-MDS/ AL after bone marrow transplant [010% (95%CI, 0–030%)] is not sufficiently different from that observed in recipients of peripheral blood or UCB transplant [056% (95%CI, 0–136%) and 056% (95%CI, 0–110%)] to reach statistical significance (P = 016). Importantly, abnormalities in chromosome 7 appear to be a common cytogenetic finding and some patients are curable simply by haematopoietic growth factor withdrawal, consistent with observations reported by others (Socie et al, 1999). In conclusion, these results provide a measure of reassurance that the incidence of DD-MDS/AL is low (1% or less) regardless of HSC source. However, longer follow up, particularly in recipients of UCB and peripheral blood, may be needed before making a definitive conclusion on the relative risks of DD-MDS/AL between the three HSC sources.
Support Supported by a Public Health Service grant P01-CA6549376518 (TED, CBG, JEWJ) from the National Cancer Institute, and the Children’s Cancer Research Fund (ACD, JEWJ).
Contributors ACD, TED, CGB and JEWJ contributed equally to study design, interpretation of data and drafting the manuscript. TED performed the statistical analysis. ACD, TED, JEWJ prepared the data file. ACD, TED, CGB, and JEWJ contributed to interpretation of data and critically reviewed the manuscript. All authors approved the final manuscript.
Conflict of interest The authors declare no conflicts of interest.
Greaves, M., Colman, S.M., Kearney, L. & Ford, A.M. (2011) Fusion genes in cord blood. Blood, 117, 369–370, author reply 370–361. Gustafsson, B., Moell, J., Leblanc, K., Barbany, G., S€ oderh€all, S. & Winiarski, J. (2011) Donor cellderived acute myeloid leukemia after second allogenic cord blood transplantation in a patient with Fanconi anemia. Pediatric Transplantation, 16, E241–E245. Hertenstein, B., Hambach, L., Bacigalupo, A., Schmitz, N., McCann, S., Slavin, S., Gratwohl, A., Ferrant, A., Elmaagacli, A., Schwertfeger, R., Locasciulli, A., Zander, A., Bornh€auser, M., Niederwieser, D., Ruutu, T., & Chronic Leukaemia
ª 2014 John Wiley & Sons Ltd, British Journal of Haematology
Working Party of the European Group for Blood and Marrow Transplantation (2005) Development of leukemia in donor cells after allogeneic stem cell transplantation–a survey of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica, 90, 969–975. Matsunaga, T., Murase, K., Yoshida, M., Fujimi, A., Iyama, S., Kuribayashi, K., Sato, T., Kogawa, K., Hirayama, Y., Sakamaki, S., Kohda, K. & Niitsu, Y. (2005) Donor cell derived acute myeloid leukemia after allogeneic cord blood transplantation in a patient with adult T-cell lymphoma. American Journal of Hematology, 9, 294–298.
3
Short Report Nakamizo, A., Akagi, Y., Amano, T., Suzuki, S.O., Otsuka, R., Abe, Y., Yoshimoto, K., Iwaki, T. & Sasaki, T. (2011) Donor-derived adult T-cell leukaemia. Lancet, 377, 1124. Rodriquez-Macias, G., Martinez-Laperche, C., Gayoso, J., Noriega, V., Serrano, D., Balsalobre, P., Munoz-Martinez, C., Diez-Martin, J.L. & Buno, I. (2013) Mutation of the NPM1 gene contributes to the development of donor-derived acute myeloid leukemia after unrelated cord blood transplantation for acute lymphoblastic leukemia. Human Pathology, 44, 1696–1699. Ruiz-Arg€ uelles, G.J., Ruiz-Arg€ uelles, A. & GarcesEisele, J. (2007) Donor cell leukemia: a critical review. Leukemia & Lymphoma, 48, 25–38. Sevilla, J., Querol, S., Molines, A., Gonzalez-Vicent, M., Balas, A., Carrio, A., Estella, J., Angel Diaz, M.
4
& Madero, L. (2006) Transient donor cell-derived myelodysplastic syndrome with monosomy 7 after unrelated cord blood transplantation. European Journal of Haematology, 77, 259–263. Socie, G., Stone, J.V., Wingard, J.R., Weisdorf, D., Henslee-Downey, P.J., Bredeson, C., Cahn, J.Y., Passweq, J.R., Rowlings, P.A., Schouten, H.C., Kolb, H.J. & Klein, J.P. (1999) Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. New England Journal of Medicine, 341, 14–21. Wang, E., Hutchinson, C.B., Huang, Q., Lu, C.M., Crow, J., Wang, F.F., Sebastian, S., Rehder, C., Lagoo, A., Horwitz, M., Rizzieri, D., Yu, J., Goodman, B., Datto, M. & Buckley, P. (2011)
Donor cell-derived leukemias/myelodysplastic neoplasms in allogeneic hematopoietic stem cell transplant recipients: a clinicopathologic study of 10 cases and a comprehensive review of the literature. American Journal of Clinical Pathology, 135, 525–540. Wiseman, D.H. (2011) Donor cell leukemia: a review. Biology of Blood and Marrow Transplantation, 17, 771–789. Yamazaki, R., Nakasone, H., Wada, H., Sakamoto, K., Ashizawa, M., Sato, M., Terasako, K., Kikuchi, M., Kimura, S., Okuda, S., Kako, S., Tanaka, Y., Tanihara, A. & Oshima, K. (2011) Recurrence of monoclonal gammopathy associated with donor-derived myelodysplastic syndrome after cord blood stem cell transplantation. Experimental Hematology, 39, 1119–1123.
ª 2014 John Wiley & Sons Ltd, British Journal of Haematology
