Bone marrow transplantation for acute nonlymphocytic leukemia in first remission: analysis of prognostic factors.
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Biomedical subjects
Publications and source records attributed to S J Forman.
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Infiltration of extrahemopoietic tissue with leukemic cells was evaluated as a prognostic indicator in 18 patients with acute leukemia undergoing bone marrow transplantation. When compared to 107 patients who did not have extramedullary leukemia at any time prior to marrow grafting, the patients with leukemic invasion into organs outside the hemopoietic system had a significant increase of leukemic recurrence and a significant decrease in survival after marrow transplantation. Extramedullary leukemia may be a negative prognostic indicator for bone marrow transplantation candidates.
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Bone marrow transplantation has become the treatment of choice for patients with severe aplastic anemia who are fortunate enough to have allogeneic sibling donors. As patients have been transplanted earlier in the course of their disease, significant improvements have been obtained in long-term survival. However, in patients who have been sensitized by previous blood product transfusions, graft rejection continues to be a significant problem and second transplants when performed are frequently unsuccessful. This case report deals with a patient with myositis ossificans progressiva (MOP) who developed severe idiopathic aplastic anemia. He rejected his first graft after 160 days. However, he was successfully reingrafted with marrow from the same donor using a different conditioning regimen.
Of 33 patients who had undergone allogeneic bone marrow transplantation during first complete remission of acute nonlymphocytic leukemia, 21 patients have now been followed in continued complete remission for 6-64 mo (median greater than 18 mo) without maintenance chemotherapy. The median age of the surviving patients is 27 yr. Transplant-related complications occurring throughout the first year after marrow grafting were fatal in 7 patients, and leukemic recurrence led to the death of 5 patients. The actuarial long-term disease-free survival is 60% and the actuarial remission rate is 79%.
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Although rare cases of chronic lymphocytic leukemia (CLL) of the T-cell type have been reported, CLL is more commonly found to be a neoplastic lymphoproliferative disease of B-cell origin. In this article, we describe a patient with long-standing CLL that was immunologically shown to be of the B-cell type, who, during the course of his disease, developed cutaneous T-cell lymphoma (CTCL), which was shown to be of the helper/inducer subtype. The neoplastic lymphoid cells in the skin infiltrate differed morphologically and immunologically from those in the peripheral blood. The occurrence of CTCL during this patient's clinical course represents a second neoplasm arising from a different cell line, rather than a tissue manifestation of the patient's CLL. To our knowledge, this is the first report in which the occurrence of CTCL is documented in a patient with immunologically known B-cell CLL. In addition to establishing the presence of B-cell CLL and CTCL of the helper/inducer T-cell type in the same patient, this case report demonstrates the usefulness and necessity of evaluating lymphoproliferative disorders by means of a multidisciplinary approach.
Fifteen adult patients with biopsy-proven convoluted T-lymphoblastic lymphoma were treated with an aggressive regimen, modified from the LSA2-L2 protocol used for childhood lymphoma. The treatment schema consisted of induction phase, including cyclophosphamide, vincristine, prednisone, adriamycin, and 2000 rads to mediastinum, as well as intrathecal methotrexate. Consolidation phase included cytosine arabinoside, 6-thioguanine, L-asparaginase, and CCNU, along with cranial irradiation and further intrathecal methotrexate. Maintenance consisted of cyclical chemotherapy and intrathecal methotrexate, continuing for a total of 3 yr. Median age in the group was 25 yr (range 16-73). There were 8 males and 7 females. At diagnosis, 9 patients had mediastinal involvement, and 9 had bone marrow involvement. Five of these demonstrated malignant cells in the peripheral blood. Complete clinical response was attained in 11 patients. Three patients achieved partial response. Four complete responders have relapsed, 1 in the central nervous system at 6 mo. and 1 in nodal sites at 3 mo, 1 in multiple sites at 24 mo. and 1 in bone marrow at 42 mo while off all chemotherapy for 6 mos. At this time, median survival of all patients is 28.3 mo. and median relapse-free survival is 21 mo. The median survival for complete responders in excess of 71 mo. while the median relapse-free survival for this group is 41 mo.
We have studied the clinical and pathologic features of three patients with a distinctive non-Hodgkin's lymphoma of the diffuse mixed cell type. The tumors were characterized by a mixture of lymphoid cells of widely varying size and degree of nuclear transformation. A distinctive feature of the neoplastic cells was the presence of cerebriform nuclear contours identical to those seen in mycosis fungoides. Immunologic studies performed on lymph nodes from two patients revealed that the neoplastic cells were T-cells. Characteristic clinical features of the patients were an advanced stage of disease at diagnosis, absence of skin lesions, presence of lung involvement, poor response to aggressive chemotherapy, and a short survival time (9-13 months). The features described closely resemble those of the pleomorphic variant of Japanese adult T-cell leukemia-lymphoma.
Allogeneic and syngeneic bone marrow transplantation has developed into an important treatment for hematologic malignancies such as acute myelogenous or lymphoblastic leukemia, chronic granulocytic leukemia in accelerated phase, acute malignant myelosclerosis, and various forms of lymphoma. So far, more than 500 patients with these disorders have been transplanted at centers throughout the world. Marrow transplantation is still surrounded by several significant clinical problems. However, optimal results are obtained when marrow grafting is performed early during the clinical course of the respective disorders.
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Human cyclic neutropenia shows many features in common with the animal model of cyclic neutropenia in grey collie dogs. Until now, however, evidence was lacking that cyclic neutropenia in man as in the dog is caused by a defect in a transplantable hematopoietic stem cell. A patient is presented who, while undergoing bone marrow transplantation as treatment for acute lymphoblastic leukemia in relapse, acquired cyclic neutropenia from her histocompatible sibling donor.