Imatinib Mesilate Versus Allogeneic Bone Marrow Transplantation for Patients with Chronic Myeloid Leukemia in First Chronic Phase - A Brazilian Point of View.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1096-1096
Author(s):  
Henrique Bittencourt ◽  
Vaneuza Funke ◽  
Laura Fogliatto ◽  
Simone Magalhaes ◽  
Daniela Setubal ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Transplantation ◽  
Median Time ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Chronic Phase ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
First Line

Abstract Imatinib has profoundly change indication of allogeneic bone marrow transplantation (alloBMT) worldwide for CML and is now the first line of treatment in most countries. However, in Brazil, Imatinib for CML in first chronic phase is provided by Federal Health Agency only for patients refractory/intolerant to interferon (IFN). In order to study results of treatment with imatinib and alloBMT in this particular scenario we retrospectively analyzed 266 patients treated for CML in first chronic phase (less than 60 years-old) in three different institutions in Brazil. End points were event free survival (EFS = absence of hematological response, lost of hematological/cytogenetic response, relapse in accelerated phase/blast crisis or death) and overall survival (OS). From jan/2001 to dec/2006, 176 patients received imatinib 400 mg after failure or intolerance to IFN. Median time from diagnosis to imatinib treatment was 19 months (range: 2 to 205). At the same period of time, 90 patients received an allo-BMT from an HLA-matched sibling (n=83) or an unrelated donor (n=7). Patients receiving peripheral blood stem cell or umbilical cord blood were excluded. Eighty-two patients received busulfan+cyclophsphamide as conditioning regimen and all patients received cyclosporin+methotrexate±steroids as GVHD prophylaxis. Median time from diagnosis to allo-BMT was 16 (range: 5 to 104) months. Gender distribution was similar between groups. Imatinib group had a higher median age (40.7 vs. 32.8 years, P<0.001). With a median follow up of 3 years, 5-year estimate EFS was 67.6% for patients receiving imatinib and 51.8% for patients receiving an allo-BMT (P=0.0002). Estimate overall survival at 5 years was 92.7% for patients treated with imatinib and 58.8% for patients receiving an allo-BMT (P<0.0001). Allo-BMT should be no more recommended as a first line alternative treatment, even if imatinib is available only for patients refractory/intolerant to IFN. Impressively, OS in Imatinib group were quite similar to those seen at the imatinib arm of IRIS study (Druker BJ et al. N Engl J Med2006; 355: 2408).

scholarly journals Use of alpha interferon for the treatment of relapse of chronic myelogenous leukemia in chronic phase after allogeneic bone marrow transplantation

Blood ◽  
1992 ◽  
Vol 80 (6) ◽  
pp. 1437-1442 ◽  
Author(s):  
CS Higano ◽  
WH Raskind ◽  
JW Singer
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Chronic Phase ◽  
Allogeneic Bone Marrow ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Sex Marker

Eighteen patients with relapse of chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation (BMT) were treated with recombinant human alpha 2a interferon (IFN). Relapse was defined as greater than 90% metaphases containing the Philadelphia chromosome (Ph) and hematologic abnormalities consistent with chronic-phase (CP) CML. There were 11 males and seven females, with a median age of 38 years (range, 3 to 55). Three patients relapsed after second BMT. Only one patient had received T-cell-depleted marrow initially. The initial IFN dose of 3 x 10(6) U/m2/d was escalated to the maximum tolerated dose or to a maximum of 6 x 10(6) U/m2/d. IFN controlled the white blood cell (WBC) counts in 14 of 16 patients who had abnormal counts, and in all six patients with an elevated platelet count. Six patients (33%) have had a complete disappearance of the Ph and two have had a partial response (less than 35% Ph+ metaphases). One patient has a decrease in Ph+ metaphases after 9 months of IFN. Five patients had no significant cytogenetic response after 9 to 12 months, and four developed clinical accelerated phase or blast crisis after 3 to 6 months on therapy. Of four patients with a sex marker, the Ph- population was of donor origin in three and of host origin in one. Clonal cytogenetic abnormalities other than Ph were present in 13 patients and did not predict for lack of response to IFN. IFN is effective in suppressing the Ph clone in some patients who relapse with CML after allogeneic BMT and controls the blood counts in the majority.

Interferon- Before Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia Does Not Affect Outcome Adversely, Provided It Is Discontinued at Least 90 Days Before the Procedure

Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3668-3677 ◽  
Author(s):  
Rüdiger Hehlmann ◽  
Andreas Hochhaus ◽  
Hans-Jochem Kolb ◽  
Jörg Hasford ◽  
Alois Gratwohl ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Chronic Phase ◽  
Observation Time ◽  
Allogeneic Bone Marrow ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone

Abstract The influence of interferon- (IFN) pretreatment on the outcome after allogeneic bone marrow transplantation (BMT) in chronic myelogenous leukemia (CML) is controversial. One goal of the German randomized CML Studies I and II, which compare IFN ± chemotherapy versus chemotherapy alone, was the analysis of whether treatment with IFN as compared to chemotherapy had an influence on the outcome after BMT. One hundred ninety-seven (23%) of 856 Ph/bcr-abl–positive CML patients were transplanted. One hundred fifty-two patients transplanted in first chronic phase were analyzed: 86 had received IFN, 46 hydroxyurea, and 20 busulfan. Forty-eight patients (32%) had received transplants from unrelated donors. Median observation time after BMT was 4.7 (0.7 to 13.5) years. IFN and chemotherapy cohorts were compared with regard to transplantation risks, duration of treatments, interval from discontinuation of pretransplant treatment to BMT, conditioning therapy, graft-versus-host disease prophylaxis and risk profiles at diagnosis and transplantation, and IFN cohorts also with regard to performance and resistance to IFN. Outcome of patients receiving related or unrelated transplants pretreated with IFN, hydroxyurea, or busulfan was not significantly different. Five-year survival after transplantation was 58% for all patients (57% for IFN, 60% for hydroxyurea and busulfan patients). The outcome within the IFN group was not different by duration of prior IFN therapy more or less than 5 months, 1 year, or 2 years. In contrast, a different impact was observed in IFN-pretreated patients depending on the time of discontinuation of IFN before transplantation. Five-year survival was 46% for the 50 patients who received IFN within the last 90 days before BMT and 71% for the 36 patients who did not (P = .0057). Total IFN dosage had no impact on survival after BMT. We conclude that outcome after BMT is not compromised by pretreatment with IFN if it is discontinued at least 3 months before transplantation. Clear candidates for early transplantation should not be pretreated with IFN.

scholarly journals Treatment of chronic myeloid leukemia with allogeneic bone marrow transplantation after preparation with BuCy2

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1352-1357
Author(s):  
JC Biggs ◽  
J Szer ◽  
P Crilley ◽  
K Atkinson ◽  
K Downs ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Chronic Phase ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Significant Difference ◽  
Total Body

One hundred fifteen patients with chronic myelocytic leukemia (CML) were administered busulphan 4 mg/kg for 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from histocompatible sibling donors. For 62 patients in chronic phase, 26 in accelerated phase, and 27 in blast transformation, the actuarial survival at 3 years was 58%, 41%, and 25%, respectively. Actuarial probability of relapse was 3%, 12%, and 27%, respectively. Only two patients in chronic phase showed a transient cytogenetic relapse and one of these died from subsequent transplant-related complications, whereas the other remains cytogenetically normal 697 days posttransplant. Patients who were transplanted within 1 year of diagnosis in chronic phase had a survival of 70% compared with 40% when transplanted beyond 1 year from diagnosis. This significant difference in survival was due to transplant-related complications and was correlated with previous exposure to high doses of busulphan. This study indicates that BuCy2 is a useful conditioning regimen for marrow transplantation in patients with CML and results in similar survival statistics and transplant-related mortality as would be expected with conditioning regimens containing total body irradiation. It is possible that relapse after BuCy2 may be lower than expected with regimens containing total body irradiation, but larger analyses are required.

scholarly journals Cytogenetic conversion following allogeneic bone marrow transplantation for advanced chronic myelogenous leukemia

Blood ◽  
1981 ◽  
Vol 58 (5) ◽  
pp. 1050-1052 ◽  
Author(s):  
PB McGlave ◽  
WJ Miller ◽  
DD Hurd ◽  
DC Arthur ◽  
T Kim
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Blast Crisis ◽  
Allogeneic Bone Marrow Transplantation ◽  
Chronic Phase ◽  
Allogeneic Bone Marrow ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone

We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allogeneic bone marrow transplantation after preparation with busulfan, vincristine, cyclophosphamide, and fractionated total body irradiation. Engraftment and conversion to normal chromosome patterns after transplantation occurred in all five patients. None of the patients reverted to an abnormal chromosome pattern of demonstrated clinical or hematologic evidence of recurrent disease during the course of this study; however, longest survival from transplant was 248 days. Allogeneic bone marrow transplantation can eradicate the abnormal clone even in far advanced chronic myelogenous leukemia and can provide normal hematopoiesis. We suggest that clinical complications of chemotherapeutic toxicity and infection were responsible for the short survival in this group of patients, and that these complications could be decreased by performing transplantation in the chronic phase or early accelerated phase of the disease.

scholarly journals Use of alpha interferon for the treatment of relapse of chronic myelogenous leukemia in chronic phase after allogeneic bone marrow transplantation

Blood ◽  
1992 ◽  
Vol 80 (6) ◽  
pp. 1437-1442 ◽  
Author(s):  
CS Higano ◽  
WH Raskind ◽  
JW Singer
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Chronic Phase ◽  
Allogeneic Bone Marrow ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Sex Marker

Abstract Eighteen patients with relapse of chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation (BMT) were treated with recombinant human alpha 2a interferon (IFN). Relapse was defined as greater than 90% metaphases containing the Philadelphia chromosome (Ph) and hematologic abnormalities consistent with chronic-phase (CP) CML. There were 11 males and seven females, with a median age of 38 years (range, 3 to 55). Three patients relapsed after second BMT. Only one patient had received T-cell-depleted marrow initially. The initial IFN dose of 3 x 10(6) U/m2/d was escalated to the maximum tolerated dose or to a maximum of 6 x 10(6) U/m2/d. IFN controlled the white blood cell (WBC) counts in 14 of 16 patients who had abnormal counts, and in all six patients with an elevated platelet count. Six patients (33%) have had a complete disappearance of the Ph and two have had a partial response (less than 35% Ph+ metaphases). One patient has a decrease in Ph+ metaphases after 9 months of IFN. Five patients had no significant cytogenetic response after 9 to 12 months, and four developed clinical accelerated phase or blast crisis after 3 to 6 months on therapy. Of four patients with a sex marker, the Ph- population was of donor origin in three and of host origin in one. Clonal cytogenetic abnormalities other than Ph were present in 13 patients and did not predict for lack of response to IFN. IFN is effective in suppressing the Ph clone in some patients who relapse with CML after allogeneic BMT and controls the blood counts in the majority.

scholarly journals Allogeneic bone marrow transplantation as treatment for accelerating chronic myelogenous leukemia

Blood ◽  
1984 ◽  
Vol 63 (1) ◽  
pp. 219-222 ◽  
Author(s):  
PB McGlave ◽  
DC Arthur ◽  
D Weisdorf ◽  
T Kim ◽  
A Goldman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Blast Crisis ◽  
Allogeneic Bone Marrow Transplantation ◽  
Chronic Phase ◽  
Allogeneic Bone Marrow ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone

Abstract Sixteen patients with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) when they presented with or developed objective signs suggesting acceleration of disease. Patients have been followed for a median of 515 days (range 216–806 days). Seven patients are alive from 319 to 732 days (median 538 days). Four patients are in complete remission 501–732 days after BMT. Three patients have developed cytogenetic evidence of relapse after BMT; however, these patients are alive and not dependent on therapy and have normal activity levels at 319, 515, and 550 days following BMT. Three additional patients have developed cytogenetic and hematologic evidence of relapse after BMT, progressed to blast crisis, and died. Six patients have died of other causes. Allogeneic BMT can eradicate the abnormal clone and provide normal hematopoiesis when performed during the accelerated phase of CML; however, this approach is associated with relapse and with relatively high mortality. The long-term efficacy of this approach and the relative efficacy of transplant during acceleration rather than during the chronic phase of CML have yet to be established.

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