scholarly journals Allogeneic stem-cell transplantation in patients with AML and MDS using myeloablative versus reduced-intensity doses of intravenous busulfan (Busulfex): The role of dose intensity

2005 ◽  
Vol 11 (2) ◽  
pp. 59 ◽  
Author(s):  
A. Shimoni ◽  
M. Yeshurun ◽  
I. Hardan ◽  
A. Avigdor ◽  
N. Shem-Tove ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Dose Intensity ◽  
Reduced Intensity

Allogeneic Stem-Cell Transplantation in Patients with AML and MDS Using Myeloablative Versus Reduced-Intensity Doses of Intravenous Busulfan : The Role of Dose Intensity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2308-2308
Author(s):  
Avichai Shimoni ◽  
Moshe Yeshurun ◽  
Izhar Hardan ◽  
Abraham Avigdor ◽  
Noga Shem-Tov ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Allogeneic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Dose Intensity ◽  
Refractory Disease ◽  
Secondary Aml ◽  
Reduced Intensity

Abstract Allogeneic stem cell transplantation (SCT) is a potentially curative approach in patients (pts) with AML and MDS. Intravenous busulfan (Busulfex, ivBu) was shown to reduce treatment-related mortality (TRM) and improve outcome after standard ablative conditioning. Reduced-intensity regimens allows SCT in pts not eligible for standard conditioning. It is not yet well established what are the dose intensities of ivBu predicting of better outcome in different settings. Eighty-six pts were included in this analysis; median age 50 years (range, 18–69). Seventy-one had AML; 31 of them had secondary AML following prior MDS (n=19) or prior chemotherapy (n=12, including 6 prior autologous SCT), and 15 had MDS (all with excess of blasts). The donors were HLA-matched siblings (n=42), 1-Ag mismatched relatives (n=6) or matched-unrelated (n=38). Thirty-six pts were in first or second remission at the time of SCT, or with less than 10% marrow blasts, 32 were chemo-refractory, and 18 had untreated MDS or relapsed AML and > 10% marrow blasts. Forty-two pts had myeloablative conditioning with ivBu (12.8 mg/kg) and cyclophosphamide. Forty-four pts considered not eligible for myeloablative therapy due to advanced age, comorbidities or extensive prior therapy were given fludarabine and reduced intensity doses of ivBu (6.4–12.8 mg/kg). With a median follow-up of 13 months, the 1-year overall (OS) and disease-free survival (DFS) rates of all pts were 47% and 44%, respectively. The cumulative incidence of TRM was relatively low at 17% and relapse rate was 40%. The most important predictive factor for survival in multivariant analysis was chemo-refractory disease at SCT (HR 3.2, p=0.001). Age, gender, secondary AML/MDS, donor type and conditioning regimen used were not significant. In particular there was no difference in survival between pts given different doses of ivBu. The OS and DFS of pts given 12.8 mg/kg (Bu16) (with cyclophosphamide or fludarabine) were 47% and 45%, compared with 50% and 45% in pts given 6.4–9.6 mg/kg (Bu8–12). Pts given Bu16 had higher risk of TRM (21% vs 7%) and lower relapse rate (33% vs 50%), not reaching statistical significance. However, the conditioning regimen had a significant influence when only pts with chemo-refractory disease were analyzed. OS, DFS, TRM and relapse rates were 39%, 38%, 26%, and 36% in pts given Bu16 compared with 0% (p=0.06), 0% (p=0.06), 19% (p=NS), and 81% (p=0.03) after Bu8–12, respectively. ivBu dose intensity did not influence outcome in chemo-sensitive disease. Pts previously untreated with > 10% marrow blasts had similar outcome to pts with chemo-sensitive disease if given Bu16, but similar to refractory disease if given Bu8–12. In conclusion, ivBu containing regimens are well tolerated with relatively low TRM rates, in particular in chemo-sensitive disease, and after reduced intensity conditioning. Busulfan dose intensity is not predictive of outcome in chemo-sensitive disease. However, pts with chemo-refractory or untreated disease could only be salvaged if given myeloablative doses of ivBu. Pts considered not eligible for standard ablative conditioning tolerated fludarabine and myeloablative doses of ivBu relatively well, and could be salvaged with this regimen even when treated for chemo-refractory disease. TRM remains acceptable even in these high-risk settings. Randomized studies will be needed to further determine the best dose-intensity in each setting.

Prognostic role of PET scanning before and after reduced-intensity allogeneic stem cell transplantation for lymphoma

Blood ◽  
2010 ◽  
Vol 115 (14) ◽  
pp. 2763-2768 ◽  
Author(s):  
Jonathan R. Lambert ◽  
Jamshed B. Bomanji ◽  
Karl S. Peggs ◽  
Kirsty J. Thomson ◽  
Ronjon K. Chakraverty ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Prospective Trial ◽  
Ct Scanning ◽  
Ct Scans ◽  
Pet Scanning ◽  
Reduced Intensity

Abstract Allogeneic stem cell transplantation (SCT) is an established therapy for patients with relapsed lymphoma, but the role of positron emission tomography (PET) scanning preallogeneic and postallogeneic SCT is uncertain. We investigated whether pretransplantation PET status predicted outcome after allogeneic SCT and whether PET surveillance after transplantation provided additional information compared with computed tomography (CT) scanning. Eighty consecutive patients with lymphoma who received a reduced-intensity allogeneic SCT were entered onto a prospective trial. PET and CT scans were performed before transplantation and up to 36 months after transplantation. Forty-two patients were PET-positive before transplantation. Pretransplantation PET status had no significant impact on either relapse rate or overall survival. Thirty-four relapses were observed, of which 17 were PET-positive with a normal CT scan at relapse. Donor lymphocyte infusion (DLI) was administered in 26 episodes of relapse and was guided by PET alone in 14 patients. These findings suggest that, in contrast to autologous SCT, pretransplantation PET status is not predictive of relapse and survival after allogeneic SCT for lymphoma. Posttransplantation surveillance by PET detected relapse before CT in half of episodes, often allowing earlier administration of DLI in patients with recurrent lymphoma, and permitted withholding of potentially harmful DLI in those with PET-negative masses on CT scans.

Allogeneic Hematopoietic Stem-Cell Transplantation in AML and MDS Using Myeloablative Versus Reduced Intensity Conditioning: The Role of Dose-Intensity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 47-47 ◽  
Author(s):  
Avichai Shimoni ◽  
Izhar Hardan ◽  
Noga Shem-Tov ◽  
Moshe Yeshurun ◽  
Ronit Yerushalmi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Dose Intensity ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Low Toxicity ◽  
Active Disease ◽  
Reduced Intensity

Abstract Allogeneic stem-cell transplantation (SCT) with both myeloablative and reduced-intensity conditioning (RIC) is effective therapy in AML/MDS. However, the relative merits of each may differ in different settings. To define the role of dose-intensity we analyzed SCT outcomes of 112 consecutive patients (pts) with AML/MDS transplanted over a 5-year period. The median age was 50 years (18–70). Eighty-five patients had AML (39 secondary) and 17 had MDS (all with excess of blasts). Fifty-eight had active disease at SCT (>10% marrow blasts) and 54 were in remission. The donor was HLA-matched sibling (n=58), 1-ag mismatched related (n=6) and matched-unrelated (n=48). Forty-five pts met eligibility criteria for standard myeloablative conditioning and were given intravenous-busulfan (12.8 mg/kg) and cyclophosphamide (ivBuCy). Sixty-seven pts were considered non-eligible for standard myeloablation due to advanced age (over 55 years for sibling SCT or over 50 years for mismatched or unrelated SCT), extensive prior therapy, organ dysfunction, recent fungal infection or poor performance status. These pts were given RIC with fludarabine and intravenous-busulfan (6.4 mg/kg, FB2, n=41) or modified myeloablative regimen with fludarabine and myeloablative doses of intravenous-busulfan (12.8 mg/kg, FB4, n=26). The median age of this group was 55 years compared with 42 years in the first group, and a larger proportion had SCT from unrelated donors. With a median follow-up of 22 months (2-62), 63 pts are alive and 49 have died (34 relapse, 15 non-relapse causes). Overall survival (OS) at 2 years was 50%, 49%, and 47% after ivBuCy, FB4, and FB2, respectively (p=NS). Non-relapse mortality was higher after ivBuCy, 22% Vs 8% and 8%, respectively (p=0.05) although these patients were younger and in a better medical condition. This difference was related to higher risk of acute GVHD grade III-IV after ivBuCy while deaths due to organ toxicity were rare in all groups. Relapse rates were lower after ivBuCy but not reaching statistical significance. Active disease at SCT was the most significant predictor of reduced survival in multivariable analysis (HR 4.5, p=0.0001). SCT from unrelated donor and poor prognosis cytogenetics had borderline significance while advanced age and secondary disease had no prognostic significance. Myeloablative and RIC regimens had similar outcomes when leukemia was in remission at SCT with a trend for better outcome with RIC; estimated 2-year OS been 60%, 68% and 80% after ivBuCy, FB4, and FB2, respectively (p=NS). However patients with active disease could only be salvaged by myeloablative conditioning (classical or modified). Among the later group, OS was 45% and 39% after ivBuCy and FB4, respectively, but no FB2 recipient survived (p=0.02). These observations suggest that RIC is associated with favorable outcome and low toxicity in pts in remission at SCT and therefore can be further studied in prospective trials comparing it to myeloablative regimens even in pts eligible for the later. However, RIC is a poor option for pts with active disease. Those not eligible for standard myeloablation could still tolerate modified myeloablation and enjoy its merits. The modified myeloablative regimen has low toxicity and similar cytoreductive effect and therefore can be further studied in prospective studies comparing it to standard myeloablative regimens even in pts eligible for the later.

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