Cytogenetic Relapse Research Articles

Cytogenetic patterns following bone marrow transplantation for chronic granulocytic leukemia

Allogeneic bone marrow transplantation (BMT) is the only treatment with a potential to cure chronic granulocytic leukemia (CGL). Cytogenetic markers, including the Philadelphia chromosome (Ph), t(9;22)(q34;q11), allow follow-up of these patients after BMT for engraftment and remission status. A variety of cytogenetic patterns have been observed after BMT for CGL. A number of patients experience cytogenetic relapse or mixed chimerism with normal cytogenetics. Furthermore, these types of complications may increase after T-cell depleted BMT. We have closely followed six patients with Ph-positive CGL treated with T-cell depleted bone marrow for 169–720 days after BMT. A number of different cytogenetic patterns were found. The first patient, transplanted while in accelerated phase, relapsed at 155 days with the same clonal abnormalities and died in blast crisis. Four other patients were found to have cytogenetic relapses between days +41 and +233. In every case the Ph reappeared along with other clonal and nonclonal abnormalities, some of which were transient. All four patients presented with hematologic relapse several months after cytogenetic relapse. The final patient has mixed chimerism with Ph-negative cells and continues to be in clinical remission. Close cytogenetic follow-up of CGL patients after BMT can provide important information about early changes in engraftment and remission status.

Competition between recipient and donor cells after bone marrow transplantation for chronic myeloid leukaemia.

The cytogenetic and clinical course of three patients allografted for Ph positive chronic myeloid leukaemia are reported. All patients had a peculiar pattern of relapse. Two out of three patients had donor marrow graft pretreated with monoclonal antibody for graft versus host prevention. The cytogenetic relapse was invariably associated with major morphological changes in the marrow indicating that these were also haematological relapses. However, no changes in the peripheral blood count were observed. When relapse occurred in these patients, Ph positive marrow metaphases and host red blood cells ranged from 75% to 100% of the total cell population: thereafter they spontaneously reverted to complete chimaerism. Therefore the presence of leukaemic cells even in considerable amount was not sufficient, per se, to prevail over normal marrow. In addition these observations indicate that relapse was not associated with elimination of the graft: while haemopoiesis was entirely of recipient origin the donor normal stem cells were present and vital although functionally silent. These data suggest that, although TBI remains the more effective tool for eradicating the majority of leukaemic cells, haemopoietic competition between host and donor marrow may have a major impact on leukaemic relapse.

Competition between recipient and donor cells after bone marrow transplantation for chronic myeloid leukaemia

The cytogenetic and clinical course of three patients allografted for Ph positive chronic myeloid leukaemia are reported. All patients had a peculiar pattern of relapse. Two out of three patients had donor marrow graft pretreated with monoclonal antibody for graft versus host prevention. The cytogenetic relapse was invariably associated with major morphological changes in the marrow indicating that these were also haematological relapses. However, no changes in the peripheral blood count were observed. When relapse occurred in these patients, Ph positive marrow metaphases and host red blood cells ranged from 75% to 100% of the total cell population: thereafter they spontaneously reverted to complete chimaerism. Therefore the presence of leukaemic cells even in considerable amount was not sufficient, per se, to prevail over normal marrow. In addition these observations indicate that relapse was not associated with elimination of the graft: while haemopoiesis was entirely of recipient origin the donor normal stem cells were present and vital although functionally silent. These data suggest that, although TBI remains the more effective tool for eradicating the majority of leukaemic cells, haemopoietic competition between host and donor marrow may have a major impact on leukaemic relapse.

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A retrospective analysis is presented of results obtained with allogeneic bone marrow transplantation (BMT) in three phases of Philadelphia chromosome-positive chronic granulocytic leukemia. At BMT, 23 patients were in blastic phase (BP), 33 were in accelerated phase (AP), and 45 were in chronic phase (CP). With a follow-up time of 1-8 years after BMT, the probability of long-term survival was 14, 10, and 58%, respectively, for patients transplanted in BP, AP, or CP. The probability of cytogenetic relapse with or without clinical hematologic relapse at 3 years after BMT was 80, 38, and 31%, respectively, for patients transplanted in BP, AP, or CP. Splenectomy did not influence posttransplant survival. Given the dismal prognosis on conventional therapy, patients younger than 50 in BP or AP should be considered for BMT. For the patient in CP, BMT offers the possibility of cure but with a significant risk of early death. Patients under 40 who fully understand the risks and potential benefits of BMT should be offered BMT early in CP before any change to AP occurs.

Treatment of Chronic Granulocytic Leukemia with Chemoradiotherapy and Transplantation of Marrow from Identical Twins

Twelve patients in the chronic phase of Ph1 (Philadelphia)-positive chronic granulocytic leukemia (CGL) received chemoradiotherapy and marrow from their normal, identical twins. All had a complete remission, with disappearance of all Ph1-positive cells. One patient died of pneumonitis while in remission. Three had a cytogenetic relapse 22 to 30 months after grafting; only one of these three entered blast crisis and died. Eight remain in complete remission 21 to 65 months (median, 30) after transplantation. Thus, the Ph1-positive clone can be ablated and blast crisis delayed or prevented. Of 10 patients with CGL who received transplants during the terminal phase, eight died soon after, one is in complete remission 11 months after receiving a second graft, and one remains in complete remission 71 months after transplantation. This experience suggests to us that every patient with CGL and an identical twin should receive a marrow graft, preferably in the chronic phase. On the basis of our results, trials of allogeneic-marrow transplantation for CGL seem justified.