Original Article
Brief Report
Donor-Derived Acute Promyelocytic Leukemia in a Liver-Transplant Recipient
N Engl J Med 1999; 341:807-813September 9, 1999
- Article
The long-term survival of donor lymphoid cells in recipients of solid-organ transplants or of fetal lymphocytes that cross the placenta and enter the maternal circulation has been established,1-3 but the fate of other hematopoietic progenitors in organ allografts, especially those of the myeloid lineage, is not known. We describe a case in which acute promyelocytic leukemia developed in a recipient of a liver transplant two years after transplantation. The leukemic clone had genetic and phenotypic markers of the donor, a previously healthy 16-year-old boy who died of a head injury. Our findings indicate that leukemic transformation of donor myeloid cells that were resident in the transplanted liver occurred in this patient.
Case Report
A 57-year-old woman presented with fatigue, palpitations, malaise, and diarrhea. She had a history of primary biliary cirrhosis and had received a liver transplant two years earlier from an unrelated 16-year-old boy who suffered a head injury while playing football and subsequently died of a subdural hematoma. The patient had two episodes of acute graft rejection 2.5 and 17 months after transplantation but never had symptoms or signs of graft-versus-host disease. At the time of the most recent presentation, she was taking prednisone (7.5 mg per day) and cyclosporine (100 mg twice daily) for post-transplantation immunosuppression. The patient had no history of exposure to radiation or alkylating agents and no family history of cancer.
The patient appeared pale and ill and had cushingoid features. There were multiple ecchymoses on her arms and legs. There was no mucosal bleeding or gingival hyperplasia. The hemoglobin level was 10.7 g per deciliter, the white-cell count was 5200 per cubic millimeter, and the platelet count was 41,000 per cubic millimeter. A blood smear showed 18 percent leukemic cells (blasts and dysplastic promyelocytes). The results of coagulation tests were consistent with findings of disseminated intravascular coagulation and were as follows: prothrombin time, 17.2 seconds (normal range, 11.0 to 13.0); partial-thromboplastin time, 29.7 seconds (normal range, 21.1 to 32.1); fibrin- and fibrinogen-degradation products, 128 mg per liter (normal value, <8 mg per liter); and fibrinogen, 35 mg per deciliter (normal range, 150 to 360 mg per deciliter).
Bone marrow aspiration and biopsy confirmed the diagnosis of the microgranular variant of acute promyelocytic leukemia, with 80 percent blast cells. As determined by flow cytometry, the leukemic cells expressed CD33, CD13, and CD34, but not HLA-DR, results that are consistent with the diagnosis of acute promyelocytic leukemia.
Antibiotics, cryoprecipitate, and heparin (600 U per hour) were administered. All-trans-retinoic acid (tretinoin), at a dose of 45 mg per square meter of body-surface area per day, was begun the day after diagnosis. Mild respiratory distress developed several hours before the first dose of all-trans-retinoic acid. The patient's clinical status deteriorated rapidly, and within 12 hours severe hypotension, respiratory distress, and metabolic acidosis (pH 6.9) developed. The white-cell count increased to 62,000 per cubic millimeter, consisting predominantly of leukemic cells. The clinical picture was consistent with the presence of sepsis, all-trans-retinoic acid syndrome (characterized by fever, respiratory distress, and pulmonary infiltrates, which develop in 25 percent of patients with promyelocytic leukemia during treatment with all-trans -retinoic acid4), or both. Despite the administration of fluid and vasopressors and mechanical ventilation, the patient's clinical status continued to deteriorate and she died within 24 hours after the first dose of all-trans -retinoic acid. Permission for autopsy was denied.
Methods
Tissue Samples
A sample of the patient's cirrhotic liver, taken at the time of the liver transplantation, was frozen within 48 hours. Liver-biopsy specimens obtained at the time of the two episodes of graft rejection were fixed in formalin and embedded in paraffin within 24 hours. Bone marrow cells aspirated at the time the patient presented with leukemia were stored in 70 percent ethanol at 4°C. Tissue from the donor before transplantation was not available.
Cytogenetic Analysis
Bone marrow samples were transported in RPMI 1640 medium with 15 percent fetal-calf serum. On arrival, cells were cultured for 24 hours at 37°C. Cells were exposed to colcemid (0.05 μg per milliliter) for 30 minutes at 37°C and harvested. Routine slide preparation and G banding were performed.
DNA and RNA Extraction
DNA and RNA were extracted from paraffin-embedded tissue specimens according to an adaptation of a previously described method5 with the use of the Puregene DNA and Purescript RNA isolation kits (Gentra Systems, Minneapolis). After DNA and RNA extraction, 10 μl of the nucleic acid solution was used for amplification.
Assay for Variable Number of Tandem Repeats and Molecular HLA Typing
A semiquantitative, nonisotopic method involving markers for variable-number tandem repeats (VNTR) and short tandem repeats for monitoring donor-cell engraftment was used as described previously.6 With the polymerase chain reaction (PCR), DNA was amplified with primers for D1S80 (chromosome 1), 33.6 (chromosome 1), and SE33 (chromosome 6) and analyzed by electrophoresis on a 6 percent polyacrylamide gel, with visualization by silver staining. We evaluated hematopoietic chimerism semiquantitatively by comparing the intensity of staining of the bands representing the alleles we studied. Molecular HLA typing was performed with the reverse-blot sequence-specific oligonucleotide-probe hybridization system developed by Roche Molecular Systems (Pleasanton, Calif.), according to the manufacturer's instructions.7,8
Analysis by Reverse-Transcription PCR
A two-step, nested reverse-transcription PCR (RT-PCR) was used to amplify chimeric PML–RARα messenger RNA (mRNA) and the reciprocal RARα–PML mRNA with published primer sequences.9,10 After amplification, the sample was electrophoresed through a 6.5 percent polyacrylamide gel, stained with ethidium bromide, and photographed.
The assay, which detects all three known isoforms of the PML–RARα fusion gene, had a sensitivity of 1 leukemic cell in 1000 normal cells. These isoforms differ only in the PML breakpoint. Exon 2 of the RARα gene is joined to exon 6 (long form) or exon 3 (short form) of the PML gene.10 A variable form has also been described.10 The clinical influence of these isoforms is controversial.11-15 The sensitivity of detection was 0.0001 for the reciprocal RARα–PML fusion gene, which is expressed in approximately 70 percent of patients with acute promyelocytic leukemia.
For all RT-PCR assays, positive control RNA from the NB4 cell line was used. This line exhibits the long form. Negative controls included both water and K562 RNA. A separate amplification of exons 1 and 2 of the N-ras gene was used to test RNA integrity.16 Precautions to eliminate the risk of contamination included the use of separate rooms for procedures performed before amplification, the use of disposable pipette tips that contained filters, and the use of water as negative controls in all amplifications.
Immunohistochemical Analysis
To demonstrate directly that the leukemic cells came from the donor, we developed an immunohistochemical method in which a monoclonal antibody directed against the donor-specific HLA marker B14 was used as a probe for donor cells, and the presence of the t(15;17) translocation was detected by in situ hybridization. The monospecific anti-B14 monoclonal antibody was selected because of the absence of this antigen on recipient cells.
Briefly, air-dried bone marrow smears were fixed in cold acetone for 10 minutes. Endogenous peroxidase activity was blocked with hydrogen peroxide and azide. After a blocking step with 1.5 percent normal goat serum at room temperature, the slides were incubated with a monospecific antihuman HLA-B14 monoclonal antibody (IgM, One Lambda, Canoga Park, Calif.) at 4°C overnight. A biotinylated goat antimouse IgM antibody and avidin–biotin complex labeled with horseradish peroxidase (Vectastatin, Vector Laboratories, Burlingame, Calif.) for 60 minutes at room temperature, followed by metal-enhanced diaminobenzidine (Pierce, Rockford, Ill.) for 60 minutes at room temperature, were used for detection. Counterstaining with hematoxylin was then performed.
Fluorescence in Situ Hybridization
To detect the t(15;17) translocation, we used dual-color fluorescence in situ hybridization with probes (Vysis, Downers Grove, Ill.) for the PML and RARα genes on chromosomes 15 and 17, respectively, hybridized to marrow cells in interphase. The melting temperature was 78°C, and the melting time was two minutes. Hybridization was performed overnight at a temperature of 37°C. 4,6-Diamidino-2-phenylindole was used as the counterstain. The Quips mFISH Capture computerized imaging system (Vysis) was used for image analysis.
Results
Cytogenetic Analysis
A male karyotype was found in 22 cells in metaphase (Figure 1AFigure 1
Cytogenetic Analysis.), all of which contained the t(15;17) translocation characteristic of acute promyelocytic leukemia: 46,XY,der(5)t(5;?9)(p15;q12), t(15;17) (q22; q12). Three residual female cells without clonal changes were also seen (46,XX) (Figure 1B).VNTR Assay
Of the three loci examined, D1S80 had a unique recipient allele and an allele shared with the donor, 33.6 had a unique donor allele and an allele shared with the recipient, and SE33 had a unique donor allele, a unique recipient allele, and a shared allele. Although no DNA from the donor before the transplantation was available, we demonstrated chimerism by comparing the DNA obtained at the time of the two liver biopsies (after transplantation) with the patient's pretransplantation DNA (Figure 2Figure 2
Variable-Number Tandem-Repeat Analysis of Samples Obtained before and after Transplantation. and Table 1Table 1
Results of DNA and RNA Analysis.). At each locus, the same mixed chimeric pattern was seen in the leukemic marrow, ruling out the possibility that the malignant clone originated from a male blood donor. The SE33 locus was chosen for semiquantitative analysis of the donor:recipient ratio (Table 1). Two and a half months after the liver transplantation, 65 to 75 percent of the DNA obtained from the liver was of donor origin. Seventeen months after transplantation, this proportion was 45 to 55 percent. This small shift probably represents repopulation of the nonhepatocytic tissue in the donor liver by cells from the recipient. The leukemic marrow had 55 to 65 percent donor DNA.RT-PCR Analysis
We investigated whether leukemic cells could be detected, before clinical presentation, in the liver-biopsy specimens obtained at the time of graft rejection. As expected, the PML–RARα gene product was detected in cells from the marrow aspirate. The patient expressed the short isoform of PML–RARα (Figure 3Figure 3
RT-PCR for the PML–RARα Fusion-Gene Product (Panel A) and the Reciprocal RARα–PML Fusion-Gene Product (Panel B).). The expected junction between exon 3 of the PML gene and exon 2 of the RARα gene was confirmed by direct sequencing of the PCR product (data not shown). In contrast with the marrow aspirate, the two liver-biopsy specimens obtained 21.5 and 7 months before the diagnosis of acute promyelocytic leukemia did not have a detectable PML–RARα fusion-gene product, in spite of the intact RNA integrity as judged by the presence of amplifiable N-ras (Figure 3 and Table 1). Therefore, leukemic infiltration of the liver at the time of the two liver biopsies was ruled out within the limits of sensitivity of this assay (1 leukemic cell in 1000 cells).Molecular HLA Typing
The results of serologic HLA typing of the donor were as follows: HLA-A1,26; HLA-B14,57; and HLA-DR6,7. (The former DR6 type has since been split into DR13 and DR14 by higher-resolution typing.) Molecular DRB1 typing of DNA derived from the recipient's cirrhotic liver before transplantation showed homozygous DRB1*08. Typing of DNA from the two liver-biopsy specimens obtained after transplantation and the leukemic marrow showed the presence of DRB1*08 from the recipient and DRB1*13,07 from the donor. The limited amount of tissue available made further molecular typing of the recipient impossible. However, HLA-B typing of the leukemic marrow showed the presence of HLA-B*14,57 (the known type of the donor) and HLA-B*07,49 or 50 (for technical reasons, it was not possible to differentiate between HLA-B*49 and HLA-B*50 in this chimeric specimen). Since a person can have only two alleles at any locus, the recipient had to have HLA-B*07,49 or 50. These results again confirm the presence in the leukemic marrow of cells with genetic markers of the donor and the recipient. Furthermore, the donor and the recipient were incompatible at both tested HLA loci.
Immunohistochemical Analysis and Fluorescence in Situ Hybridization
Leukemic cells stained for HLA-B14 (from the donor) at the surface; however, the intensity of staining varied from very dense to undetectable (Figure 4Figure 4
Analysis of the Leukemic Bone Marrow by Immunohistochemistry and Fluorescence in Situ Hybridization.). Analysis of 100 cells showed that 30 cells were negative for HLA-B14, whereas 70 cells were positive. Of the 30 HLA-B14–negative cells, 7 had evidence of a t(15;17) translocation and 23 did not (Table 2Table 2
Results of Immunohistochemical Staining and Fluorescence in Situ Hybridization. and Figure 4). The 7 cells with a hybridization signal indicating a PML–RARα fusion gene were leukemic cells morphologically, whereas the other 23 cells were not. Of the 70 HLA-B14–positive cells, 45 clearly had a fusion signal indicative of a t(15;17) translocation (Figure 4). In the other 25 HLA-B14–positive cells, the hybridization signal was obscured by the HLA-B14 staining on the surface (Table 2); however, all 70 HLA-B14–positive cells were leukemia cells morphologically. Review of the entire smear revealed that all cells with normal morphologic features, including erythroid precursors, lymphocytes, eosinophils, and megakaryocytes, were negative for HLA-B14, and all cells exhibiting a normal hybridization pattern were negative for HLA-B14.Discussion
This report describes the development of donor-derived acute promyelocytic leukemia in a female recipient of a liver transplant from a male donor. The presence of unique sex-chromosome and HLA markers, which enabled identification of donor and recipient cells, and a leukemia-specific marker — the t(15;17) translocation — provided an opportunity to pinpoint the origin of the leukemic cells in donor myeloid cells that had been transferred to the recipient in the graft two years earlier.
Several lines of evidence support the notion that the leukemic cells in the recipient came from the donor of the liver. First, cytogenetic analysis demonstrated that all leukemic cells with the t(15;17) translocation, which is pathognomonic of acute promyelocytic leukemia, had a male karyotype, whereas all cells without this translocation had a female karyotype. Second, molecular HLA typing of the leukemic marrow at two loci (HLA-B and HLA-DRB1) confirmed that both donor and recipient cells were present and showed the presence of all expected donor-specific alleles. Third, in the bone marrow, blasts and dysplastic promyelocytes expressed the donor-specific HLA marker B14, whereas residual normal hematopoietic cells did not. Fourth, leukemic cells that expressed the donor-specific HLA-B14 antigen also harbored the t(15;17) translocation, as detected by fluorescence in situ hybridization, whereas morphologically normal cells did not. Finally, quantitative VNTR analysis detected the presence of 55 to 65 percent donor DNA in the recipient's marrow, corresponding approximately to the extent of leukemic involvement estimated by morphologic examination.
Leukemia originating in donor cells has been described after bone marrow transplantation in 23 cases.17-36 Since all these cases entailed donor transplants from relatives of the recipients, mechanisms for the development of donor-cell leukemia have been thought to involve inherited genetic factors,35,37 transmissible viral agents,17,18,20,21,24,25,29,33 or the persistence of an undefined environmental factor in the marrow affecting leukemic cells.17,18,20,26,28,33 Since our patient had a liver graft from an unrelated donor and no preexisting malignant condition, these conjectures are not relevant.
Hematopoietic stem cells are present in the liver, a site of hematopoiesis in fetuses and, under certain pathologic conditions, in adults.38 Although donor-derived lymphoid cells are able to survive over the long term in the recipient of a solid-organ transplant,1 the fate of other hematopoietic lineages is unknown. Multilineage engraftment is the best indication of the persistence of multipotent stem cells, but it is very rare after solid-organ transplantation. The only well-described case38 of multilineage engraftment was a patient who underwent liver transplantation, had severe graft-versus-host disease 32 days after transplantation, and died of graft-versus-host disease on day 135. Microchimerism is another recently described phenomenon, in which foreign cells remain detectable in the host for years.2,3,39 Normal hematopoietic cells of donor origin were not detectable at the time of diagnosis of acute promyelocytic leukemia in our patient, because normal hematopoietic elements expressing the donor-specific HLA-B14 antigen were not found (Table 2 and Figure 4) and cytogenetic analysis showed no male cells with a normal karyotype (Figure 1). The presence of donor-derived leukemia two years after liver transplantation suggests the prior existence of normal donor-type myeloid precursors that underwent leukemic transformation in the recipient.
To test the validity of this conclusion, we tried to ascertain the timing of the postulated leukemic transformation. Although donor tissue was not available for testing, a complete blood count and automated differential cell count obtained before liver donation did not suggest the presence of any hematologic disorder. RT-PCR, which can detect 1 leukemic cell in a population of 1000 normal cells, failed to detect the PML–RARα fusion gene product in two liver-biopsy specimens obtained 2.5 and 17 months after transplantation. This result rules out gross leukemic infiltration of the liver at the time of the biopsies, but does not rule out the possibility of undetectable involvement in the liver or the presence of leukemic cells in another organ, such as the bone marrow.
The donor and recipient were unrelated and were incompatible for both tested HLA loci. The ability of an HLA-incompatible leukemic clone to proliferate in this patient is remarkable. Factors that may have contributed to the survival of donor leukemic cells include the immunocompromised state of the patient and the disruption of the PML gene in the donor cells. In mice, the PML gene controls the expression of major-histocompatibility-complex (MHC) class I genes.40 Our finding of low-to-variable expression of the donor-specific HLA-B14 antigen on leukemic cells is compatible with interference with expression of MHC class I genes, possibly from disruption of the PML locus. Reduced expression of HLA class I antigens on acute promyelocytic leukemia cells may have contributed to the lack of a response by the recipient's immune system.
We are indebted to Drs. J. Evan Sadler and Mary Zutter for their insightful counsel and support; to Jane Rodney and Paula Ladne for their invaluable technical assistance with immunohistochemistry and RT-PCR, respectively; and to Anajane Smith for her dedicated and skillful help with the VNTR analysis and molecular HLA typing.
Source Information
From the Departments of Medicine (I.B., M.P., M.B., S.N., R.B., J.D., D.A.), Pathology (J.H.), Pediatrics (M.S.W., R.V.R.), and Surgery (J.A.L.), Washington University School of Medicine, St. Louis; and the Fred Hutchinson Cancer Research Center, Seattle (J.P.R.).
Address reprint requests to Dr. Bodó at Euro-Med-Net, 5-7 Gyýri Ut., Budapest H-1123, Hungary, or at bodoimre@elender.hu.
- References
References
1
Rao AS ,Starzl TE ,Demetris AJ , et al. The two-way paradigm of transplantation immunology. Clin Immunol Immunopathol 1996;80:Suppl:S46-S51
CrossRef | Medline2
Artlett CM ,Smith JB ,Jimenez SA . Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N Engl J Med 1998;338:1186-1191
Full Text | Web of Science | Medline3
Bianchi DW ,Zickwolf GK ,Weil GJ ,Sylvester S ,DeMaria MA . Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acad Sci U S A 1996;93:705-708
CrossRef | Web of Science | Medline4
Frankel SR ,Eardley A ,Lauwers G ,Weiss M ,Warrell RP Jr . The “retinoic acid syndrome“ in acute promyelocytic leukemia. Ann Intern Med 1992;117:292-296
Web of Science | Medline5
Sarkar FH ,Li YW ,Crissman JD . A method for PCR sequencing of the p53 gene from a single 10-microns frozen or paraffin-embedded tissue section. Biotechniques 1993;15:36-38
Web of Science | Medline6
Smith AG ,Martin PJ ,McFarland C ,Regen L ,Hansen JA . Evaluation of engraftment in the stem cell transplant setting by PCR DNA amplification and analysis of variable number tandem repeat loci. ASHI Quarterly 1998;22:3-97
Bugawan TL ,Apple R ,Erlich HA . A method for typing polymorphism at the HLA-A locus using PCR amplification and immobilized oligonucleotide probes. Tissue Antigens 1994;44:137-147
CrossRef | Web of Science | Medline8
Erlich H ,Bugawan T ,Begovich AB , et al. HLA-DR, DQ and DP typing using PCR amplification and immobilized probes. Eur J Immunogenet 1991;18:33-55
CrossRef | Medline9
Tobal K ,Saunders MJ ,Grey MR ,Yin JA . Persistence of RAR alpha-PML fusion mRNA detected by reverse transcriptase polymerase chain reaction in patients in long-term remission of acute promyelocytic leukaemia. Br J Haematol 1995;90:615-618
CrossRef | Web of Science | Medline10
Gallagher RE ,Li YP ,Rao S , et al. Characterization of acute promyelocytic leukemia cases with PML-RAR alpha break/fusion sites in PML exon 6: identification of a subgroup with decreased in vitro responsiveness to all-trans retinoic acid. Blood 1995;86:1540-1547
Web of Science | Medline11
Gallagher RE ,Willman CL ,Slack JL , et al. Association of PML-RAR alpha fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia: an intergroup molecular study. Blood 1997;90:1656-1663
Web of Science | Medline12
Huang W ,Sun GL ,Li XS , et al. Acute promyelocytic leukemia: clinical relevance of two major PML-RAR alpha isoforms and detection of minimal residual disease by retrotranscriptase/polymerase chain reaction to predict relapse. Blood 1993;82:1264-1269
Web of Science | Medline13
Vahdat L ,Maslak P ,Miller WH Jr , et al. Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-alpha isoform, and CD13 expression in patients treated with all-trans retinoic acid. Blood 1994;84:3843-3849
Web of Science | Medline14
Fukutani H ,Naoe T ,Ohno R , et al. Isoforms of PML-retinoic acid receptor alpha fused transcripts affect neither clinical features of acute promyelocytic leukemia nor prognosis after treatment with all-trans retinoic acid. Leukemia 1995;9:1478-1482
Web of Science | Medline15
Borrow J ,Goddard AD ,Gibbons B , et al. Diagnosis of acute promyelocytic leukaemia by RT-PCR: detection of PML-RARA and RARA-PML fusion transcripts. Br J Haematol 1992;82:529-540
CrossRef | Web of Science | Medline16
Radich JP ,Kopecky KJ ,Willman CL , et al. N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance. Blood 1990;76:801-807
Web of Science | Medline17
Fialkow PJ ,Thomas ED ,Bryant JI ,Neiman PE . Leukaemic transformation of engrafted human marrow cells in vivo. Lancet 1971;1:251-255
CrossRef | Web of Science | Medline18
Thomas ED ,Bryant JI ,Buckner CD , et al. Leukaemic transformation of engrafted human marrow cells in vivo. Lancet 1972;1:1310-1313
CrossRef | Web of Science | Medline19
Goh K ,Klemperer MR . In vivo leukemic transformation: cytogenetic evidence of in vivo leukemic transformation of engrafted marrow cell. Am J Hematol 1977;2:283-290
CrossRef | Web of Science | Medline20
Elfenbein GJ ,Brogaonkar DS ,Bias WB , et al. Cytogenetic evidence for recurrence of acute myelogenous leukemia after allogeneic bone marrow transplantation in donor hematopoietic cells. Blood 1978;52:627-636
Web of Science | Medline21
Newburger PE ,Latt SA ,Pesando JM , et al. Leukemia relapse in donor cells after allogeneic bone-marrow transplantation. N Engl J Med 1981;304:712-714
Full Text | Web of Science | Medline22
Boyd CN ,Ramberg RC ,Thomas ED . The incidence of recurrence of leukemia in donor cells after allogeneic bone marrow transplantation. Leuk Res 1982;6:833-837
CrossRef | Web of Science | Medline23
Marmont A ,Frassoni F ,Bacigalupo A , et al. Recurrence of Ph'-positive leukemia in donor cells after marrow transplantation for chronic granulocytic leukemia. N Engl J Med 1984;310:903-906
Full Text | Web of Science | Medline24
McCann SR ,Lawler M ,Humphries P , et al. Recurrence of Philadelphia chromosome-positive leukemia in donor cells after marrow transplantation for chronic granulocytic leukemia: confirmation by microsatellite studies. Blood 1992;79:2803-2805
Web of Science | Medline25
Witherspoon RP ,Schubach W ,Neiman P ,Martin P ,Thomas ED . Donor cell leukemia developing six years after marrow grafting for acute leukemia. Blood 1985;65:1172-1174
Web of Science | Medline26
Smith JL ,Heerema NA ,Provisor AJ . Leukaemic transformation of engrafted bone marrow cells. Br J Haematol 1985;60:415-422
CrossRef | Web of Science | Medline27
Schmitz N ,Johannson W ,Schmidt G ,von der Helm K ,Loffler H . Recurrence of acute lymphoblastic leukemia in donor cells after allogeneic marrow transplantation associated with a deletion of the long arm of chromosome 6. Blood 1987;70:1099-1104
Web of Science | Medline28
Feig SA ,Dreazen O ,Simon M ,Wiley F ,Schreck R ,Gale RP . B cell acute lymphoblastic leukemia (ALL) in donor cells following bone marrow transplantation for T cell ALL. Bone Marrow Transplant 1988;3:331-337
Web of Science | Medline29
Witherspoon RP ,Fisher LD ,Schoch G , et al. Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia. N Engl J Med 1989;321:784-789
Full Text | Web of Science | Medline30
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 | Medline31
Palka G ,Calabrese G ,Di Girolamo G , et al. Cytogenetic survey of 31 patients treated with bone marrow transplantation for acute nonlymphocytic and acute lymphoblastic leukemias. Cancer Genet Cytogenet 1991;51:223-233
CrossRef | Web of Science | Medline32
Browne PV ,Lawler M ,Humphries P ,McCann SR . Donor-cell leukemia after bone marrow transplantation for severe aplastic anemia. N Engl J Med 1991;325:710-713
Full Text | Web of Science | Medline33
Cransac M ,Boiron JM ,Merel P , et al. Burkitt-type acute lymphoblastic leukemia in donor cells after allogeneic bone marrow transplantation for acute nonlymphoblastic leukemia. Transplantation 1993;56:120-123
CrossRef | Web of Science | Medline34
Mouratidou M ,Sotiropoulos D ,Deremitzaki K , et al. Recurrence of acute leukemia in donor cells after bone marrow transplantation: documentation by in situ DNA hybridization. Bone Marrow Transplant 1993;12:77-80
Web of Science | Medline35
Katz F ,Reeves BR ,Alexander S ,Kearney L ,Chessells J . Leukaemia arising in donor cells following allogeneic bone marrow transplantation for beta thalassaemia demonstrated by immunological, DNA and molecular cytogenetic analysis. Br J Haematol 1993;85:326-331
CrossRef | Web of Science | Medline36
Lowsky R ,Fyles G ,Minden M , et al. Detection of donor cell derived acute myelogenous leukaemia in a patient transplanted for chronic myelogenous leukaemia using fluorescence in situ hybridization. Br J Haematol 1996;93:163-165
CrossRef | Web of Science | Medline37
Brown SA ,Bashey A ,Schey SA . Donor cell leukaemia -- an unresolved problem. Eur J Haematol 1995;54:198-199
CrossRef | Web of Science | Medline38
Collins RH Jr ,Anastasi J ,Terstappen LWMM , et al. Donor-derived long-term multilineage hematopoiesis in a liver-transplant recipient. N Engl J Med 1993;328:762-765
Full Text | Web of Science | Medline39
Hohaus S ,Horvath C ,Nierhoff D , et al. Microchimerism in bone marrow-derived CD34+ cells of patients after liver transplantation. Blood 1998;92:Suppl I:132a-132a abstract.
Web of Science40
Zheng P ,Guo Y ,Niu Q , et al. Proto-oncogene PML controls genes devoted to MHC class I antigen presentation. Nature 1998;396:373-376
CrossRef | Web of Science | Medline
- Citing Articles (18)
Citing Articles
1
Laura J. Wozniak, Hui-Min Yang, Charles R. Lassman, Noah Federman, Steven S. Wu. (2011) Extramedullary Acute Myelocytic Leukemia Following Liver Transplantation for VOD With Immunodeficiency. Journal of Pediatric Gastroenterology and Nutrition 53:3, 346-349
CrossRef2
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
CrossRef3
Nan Jiang, Hua LI, Gen-Shu Wang, Jian Zhang, Jun-Feng Zhang, Shu-Hong Yi, Yang Yang, Chang-Jie Cai, Min-Qiang Lu, Gui-Hua Chen. (2009) Acute leukemia, a rare but fatal complication after liver transplantation. Leukemia Research 33:10, 1349-1351
CrossRef4
M. G. Ison, J. Hager, E. Blumberg, J. Burdick, K. Carney, J. Cutler, J. M. DiMaio, R. Hasz, M. J. Kuehnert, E. Ortiz-Rios, L. Teperman, M. Nalesnik. (2009) Donor-Derived Disease Transmission Events in the United States: Data Reviewed by the OPTN/UNOS Disease Transmission Advisory Committee. American Journal of Transplantation 9:8, 1929-1935
CrossRef5
Manish J. Gandhi, D. Michael Strong. (2007) Donor derived malignancy following transplantation: a review. Cell and Tissue Banking 8:4, 267-286
CrossRef6
Thomas Lowe, Smita Bhatia, George Somlo. (2007) Second Malignancies after Allogeneic Hematopoietic Cell Transplantation. Biology of Blood and Marrow Transplantation 13:10, 1121-1134
CrossRef7
Allan Concejero, Chao-Long Chen, Chih-Chi Wang, Shih-Ho Wang, Chih-Che Lin, Yueh-Wei Liu, Chin-Hsiang Yang, Chee-Chien Yong, Ming-Chung Wang, Hock-Liu Eng. (2007) Chronic Myeloid Leukemia After Living Donor Liver Transplantation. Transplantation 83:11, 1521-1522
CrossRef8
Gustaf Edgren, Henrik Hjalgrim, Marie Reilly, Trung Nam Tran, Klaus Rostgaard, Agneta Shanwell, Kjell Titlestad, Johanna Adami, Agneta Wikman, Casper Jersild, Gloria Gridley, Louise Wideroff, Olof Nyrén, Mads Melbye. (2007) Risk of cancer after blood transfusion from donors with subclinical cancer: a retrospective cohort study. The Lancet 369:9574, 1724-1730
CrossRef9
Taketoshi Yoshida, Hirokazu Kanegane, Keisuke Otsubo, Keiko Nomura, Shinichiro Hirokawa, Koichi Tsuneyama, Hiroto Egawa, Toshio Miyawaki. (2005) Acute lymphoblastic leukemia after living donor liver transplantation. Pediatrics International 47:5, 579-582
CrossRef10
Christian Morath, Vedat Schwenger, Jan Schmidt, Martin Zeier. (2005) Transmission of Malignancy with Solid Organ Transplants. Transplantation 80:Supplement, S164-S166
CrossRef11
Tomonobu Sato, Ryoji Kobayashi, Akihiro Iguchi, Masahide Nakajima, Saeko Koizumi, Hiroyuki Furukawa, Satoru Todoh, Kunihiko Kobayashi. (2005) Acute promyelocytic leukemia after living donor partial orthotopic liver transplantation in two Japanese girls. Leukemia & Lymphoma 46:7, 1057-1060
CrossRef12
Paola Pedotti, Francesca Poli, Elena Longhi, Sara Frison, Rossana Caldara, Stefano Chiaramonte, Eliana Gotti, Francesco Marchini, Cristina Maresca, Silvio Sandrini, Mario Scalamogna, Emanuela Taioli. (2004) Epidemiologic study on the origin of cancer after kidney transplantation. Transplantation 77:3, 426-428
CrossRef13
Mireia Cam??s, Jordi Esteve, Antoni Rimola, Luis Grande, Mar??a Rozman, Dolors Colomer, Neus Villamor, Dolors Costa, Emili Montserrat. (2004) Increased incidence of acute myeloid leukemia after liver transplantation? Description of three new cases and review of the literature1. Transplantation 77:2, 311-313
CrossRef14
H. Myron Kauffman, Maureen A. McBride, Wida S. Cherikh, Pamela C. Spain, William H. Marks, Allan M. Roza. (2002) Transplant tumor registry: donor related malignancies. Transplantation 74:3, 358-362
CrossRef15
E. J. Chow. (2002) Blood Transfusions as a Risk Factor for Non-Hodgkin's Lymphoma in the San Francisco Bay Area: A Population-based Study. American Journal of Epidemiology 155:8, 725-731
CrossRef16
Berg, Karin D., Brinster, Nooshin K., Huhn, Karen M., Goggins, Michael G., Jones, Richard J., Makary, Adel, Murphy, Kathleen M., Griffin, Constance A., Rosenblum-Vos, Lynne S., Borowitz, Michael J., Nousari, Hossein C., Eshleman, James R., . (2001) Transmission of a T-Cell Lymphoma by Allogeneic Bone Marrow Transplantation. New England Journal of Medicine 345:20, 1458-1463
Full Text17
Carlos A. Doti, Gabriel E. Gondolesi, Patricia A. Sheiner, Sukru Emre, Charles M. Miller, Louis M. Aledort. (2001) LEUKEMIA AFTER LIVER TRANSPLANT. Transplantation 72:10, 1643-1646
CrossRef18
Sigurdur Bodvarsson, William Burlingham, Satoshi Kusaka, Gholam-Reza Hafez, Bryan N. Becker, Thomas Pintar, Hans W. Sollinger, Mark R. Albertini. (2001) Donor-derived small cell lung carcinoma in a kidney transplant recipient. Cancer 92:9, 2429-2434
CrossRef
