Secondary malignancies after bone marrow transplantation in adults.

PURPOSE The records of 557 consecutive adult recipients of allogeneic-related and -unrelated and syngeneic bone marrow transplants (BMTs) were reviewed to determine the incidence of secondary cancers. PATIENTS AND METHODS Four hundred fifty-six patients were transplanted for acute lymphocytic leukemia (ALL; n = 79), acute myelogenous leukemia (AML; n = 182), and chronic myelogenous leukemia (CML; n = 195); 42 patients were transplanted for aplastic anemia (AA) and 59 for a variety of other hematologic and nonhematologic disorders, malignant and nonmalignant. Conditioning regimens included high-dose chemotherapy with or without total-body irradiation (TBI). Statistical analyses determined the cumulative incidence of developing a secondary cancer and elucidated the associated risk factors. Complete records (1 to 24 years of follow-up) on all patients were available. RESULTS Nine patients developed 10 secondary cancers for a cumulative actuarial risk of 12% (95% confidence interval [CI], 4.3 to 23.0) 11 years after transplant. The age-adjusted incidence of secondary cancer was 4.2 times higher than that of primary cancer in the general population. Eight of the 10 were epithelial in origin and three were cutaneous. TBI and acute graft-versus-host disease (GVHD) with a severity > or = grade II were associated with the development of any secondary cancer. On the other hand, chronic GVHD was a risk factor only for the development of secondary skin neoplasms. CONCLUSION Adult recipients of BMT face a significant risk of developing a secondary malignancy. Their risk is similar to that of other patients with hematologic malignancies who are treated with chemoradiotherapy only. Epithelial tumors, rather than the more commonly reported Epstein-Barr virus (EBV)-associated lymphomas, were most common. The fact that we did not routinely use T-cell-depleted marrow grafts nor anti-T-cell immunoglobulin for the treatment of acute GVHD may explain this variance.

[1]  P. Cony-Makhoul,et al.  BURKITT‐TYPE ACUTE LYMPHOBLASTIC LEUKEMIA IN DONOR CELLS AFTER ALLOGENEIC BONE MARROW TRANSPLANTATION FOR ACUTE NONLYMPHOBLASTIC LEUKEMIA , 1993, Transplantation.

[2]  Deeg Hj,et al.  Risk factors for the development of secondary malignancies after marrow transplantation. , 1993 .

[3]  D. Tritchler,et al.  Long-term results of bone marrow transplantation for patients with AML, ALL and CML prepared with single dose total body irradiation of 500 cGy delivered with a high dose rate. , 1991, Bone marrow transplantation.

[4]  P. Humphries,et al.  Donor-cell leukemia after bone marrow transplantation for severe aplastic anemia. , 1991, The New England journal of medicine.

[5]  H. Kolb,et al.  Late complications after allogeneic bone marrow transplantation for leukaemia. , 1990, Bone marrow transplantation.

[6]  H. Prentice,et al.  MYELODYSPLASIA AND ACUTE MYELOID LEUKAEMIA FOLLOWING BONE MARROW TRANSPLANTATION FOR ACUTE LYMPHOBLASTIC LEUKAEMIA: SECONDARY LEUKAEMIA OR STEM‐CELL RELAPSE? , 1989, British journal of haematology.

[7]  H. Deeg,et al.  Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia. , 1989, The New England journal of medicine.

[8]  B. Burke,et al.  Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation. , 1988, Blood.

[9]  M. Tucker,et al.  Risk of second cancers after treatment for Hodgkin's disease. , 1988, The New England journal of medicine.

[10]  P. Duffey,et al.  Decreasing risk of leukemia with prolonged follow-up after chemotherapy and radiotherapy for Hodgkin's disease. , 1987, The New England journal of medicine.

[11]  H. Deeg,et al.  Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. , 1986, The New England journal of medicine.

[12]  M. Greene,et al.  Second cancer following lymphatic and hematopoietic cancers in Connecticut, 1935-82. , 1985, National Cancer Institute monograph.

[13]  P. Neiman,et al.  Donor cell leukemia developing six years after marrow grafting for acute leukemia. , 1985, Blood.

[14]  H. Deeg,et al.  Secondary malignancies after marrow transplantation. , 1984, Experimental hematology.

[15]  S. Latt,et al.  Leukemia relapse in donor cells after allogeneic bone-marrow transplantation. , 1981, The New England journal of medicine.

[16]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[17]  S. Finch The study of atomic bomb survivors in Japan. , 1979, The American journal of medicine.

[18]  John C. Bailar,et al.  202. Note: Significance Factors for the Ratio of a Poisson Variable to Its Expectation , 1964 .

[19]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[20]  M. Horowitz,et al.  Cancer after bone marrow transplantation , 1992 .

[21]  M. Pepe,et al.  Cumulative incidence of secondary solid malignant tumors in aplastic anemia patients given marrow grafts after conditioning with chemotherapy alone. , 1992, Blood.