Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Secondary Acute Myelogenous Leukemia (AML) or High Risk Myelodysplastic Syndromes (MDS).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5416-5416
Author(s):  
Jean El-Cheikh ◽  
Catherine Faucher ◽  
Mohamad Mohty ◽  
Anne-Marie Stoppa ◽  
Marina Lafage-Pochitaloff ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Conditioning Regimen ◽  
High Risk Group ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Group 13 ◽  
Secondary Aml ◽  
Poor Risk ◽  
First Line Therapy

Abstract Secondary AML and high risk MDS represent a poor risk group of myeloid malignancies. We report here the results of a single center retrospective study of allo-SCT in 28 patients (median age, 42 y.) with secondary AML (n=19; 68%) and MDS (n=9; 22%). Eleven patients (39%) had therapy-related AML (t-AML). FAB categories included: AR/ARS: 3, AREB/AREBt: 6, M0: 1, M1–M2: 9, M4–M5: 5, M6: 3, and one patient could not be classified. Cytogenetics features were: poor risk in 20 patients (71%), normal in 5 patients (19%) and not evaluated in 3 (10%). Allo-SCT was performed as first line therapy in 9 patients (32%) of whom 7 MDS and 2 sAML. The remaining 19 patients (68%), were transplanted after initial induction chemotherapy of whom 17 sAML (89%), and 2 MDS (11%). Median interval between diagnosis and allo-SCT was 3.6 months (range, 1–12). 12 patients (43%) were in complete remission at time of allo-SCT, while 9 patients (32%) were refractory or in progression after treatment, and 7 patients (25%) had stable disease. In 25 cases (89%) donor was a HLA identical sibling, and in 3 cases (11%) a matched unrelated donor. The conditioning regimen was fully myeloablative in 19 patients (68%) including Cy-TBI or BU-Mel or a reduced intensity conditioning (RIC) in 9 patients (32%). Nineteen patients (68%) died after transplantation, of whom 12 patients from non relapse causes (GVHD: 5; infections: 6; multi-organ failure: 1). Seven patients (25%) died from relapse or progression of the disease including 5 patients (18%) with AML and 2 patients (7%) with MDS. The one-year cumulative incidence of transplant related mortality (TRM) was 38%, with TRM being significantly lower in the RIC allo-SCT group (13% vs. 43%; P=0.06). With a median follow-up of 30 months, the probability of progression after transplantation at 5 years was 51% (95%CI, 39–73). Five-year overall survival (OS) was 26% (95%CI, 13–48). Most importantly, none of the pre-transplant parameters influenced OS or DFS. In all, these results suggest that standard allo-SCT is associated with a high TRM rate not allowing a breakthrough in the outcome of patients with secondary AML and high-risk MDS. The use of a RIC regimen significantly decreased TRM in this high risk group of patients, likely representing an attractive modality to develop novel strategies and further refine the allogeneic anti-leukemic activity for a better outcome.

Allogeneic Transplantation (HCT) for Myelodysplastic Syndrome:Recent MDACC Experience.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1131-1131
Author(s):  
Uday Popat ◽  
Marcos J de Lima ◽  
Touch Ativitavas ◽  
Gabriela Rondon ◽  
Leandro de Padua Silva ◽  
...  
Keyword(s):  
High Risk ◽  
Median Time ◽  
Cumulative Incidence ◽  
Risk Group ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
High Risk Group ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Very High

Abstract BACKGROUND: Many recent advances have occurred in the field of MDS including hypomethylating agents, lenalidomide, and WHO classification. Likewise the field of HCT has also undergone major new developments including non ablative conditioning, better supportive care, better HLA typing, selection of unrelated donors and development of reduced toxicity ablative regimens like Busulfan and Fludarabine. The role of HCT therefore needs to be redefined in light of these developments. The purpose of this study is to report our recent results. PATIENTS AND METHODS: 89 consecutive patients with MDS as defined by WHO criteria treated at our institution between Jan 2002 and April 2008 are included in this report. There were 60 males and 29 female with a median age of 54 (23–67). There were 5(6%) patients with RA, 1(1%) RARS, 9(10%) RCMD, 22(25%) RAEB 1, 17(19%) RAEB 2, and 35(39%) therapy related MDS(t MDS). Their IPSS scores were 25(28%) patients with Intermediate 1, 49(55%) Intermediate 2, 15(17%) high. Their WPSS categories were 5(6%) patients Low, 9(10%) Intermediate, 49(55%) high, and 26(29%) very high. 51(57%) patients had a matched related donor and 38(43%) had an unrelated donor. Conditioning regimen were Flu/Bu in 56(63%) patients, Bu/Cy 1(1%), Flu/Mel 32(36%). According to HCT-CI index, the comorbidity scores were 0 in 16(18%) patients, 1 or 2 in 19(21%) and greater then 2 in 54(61%). Median time from diagnosis to transplant was 8 months (range 1–51 months). RESULTS: With a median follow up of 28 (3–73) months, 2 year overall(OS) and disease free survival were 54%(95% CI; 42%–66%) and 52%(95% CI; 40%–64%) respectively. Cumulative incidence of non relapse mortality at 2 years was 23% (95% CI; 16%–35%). Cumulative incidence of relapse mortality at 2 years was 23% (95% CI; 15%–34%). As per WHO grouping, OS was 63%, 60%, 46% and 48% in patients with Low blast count (RA, RARS, RAMD), RAEB1, RAEB2 and t MDS( p=0.46) respectively. WPSS score was significantly(P=0.01) predictive of overall survival (see fig): 27% surviving in very high risk group, 61% in high risk group and 78% in Low and intermediate risk group. Likewise cytogenetic risk group and IPSS were significantly predictive of survival. Donor type or graft source did not predict outcome. Five patients developed primary(3) or secondary(2) graft failure. Median time to neutrophil engraftment was 13 days (8–26 days) and to platelet engraftment was 16 days (9–89 days). CONCLUSION: These results in patients with comorbidities and with a median age of 54 years are promising. Cytogenetics and prognostic scores based on cytogenetics predict outcome after HCT. Figure Figure

scholarly journals Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1382-1388 ◽  
Author(s):  
PJ Tutschka ◽  
EA Copelan ◽  
JP Klein
Keyword(s):  
High Risk ◽  
Acute Leukemia ◽  
Marrow Transplantation ◽  
Risk Group ◽  
Chronic Phase ◽  
Length Of Hospital Stay ◽  
High Risk Group ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Standard Risk

Abstract Busulfan 16 mg/kg and cyclophosphamide 120 mg/kg were used as conditioning prior to allogeneic marrow transplantation in 50 adult patients with acute nonlymphocytic leukemia (ANLL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML). A standard risk group of 20 patients included those with acute leukemia in remission and CML in chronic phase. A high-risk group of 30 patients included individuals with refractory acute leukemia, acute leukemia in relapse, acute leukemia following preleukemia, and CML in accelerated and blastic phase. Complete remission and sustained complete engraftment were achieved in all evaluable patients. The duration of aplasia was remarkably short (median of 8 days), resulting in a low infection rate during the period of neutropenia, a reduced need for blood product support, and a short length of hospital stay. Three-year actuarial relapse-free survival in both standard-risk (88.9% +/- 10.5%) and high- risk (50.5% +/- 9.6%) groups compares favorably with that reported with total body irradiation (TBI) containing regimens.

Maintenance Therapy with 5-Azacytidine (5-AC) after Allogeneic Stem Cell Transplantation (allo-SCT) for Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS): A Dose and Schedule Finding Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3668-3668 ◽  
Author(s):  
Andres O. Soriano ◽  
Richard Champlin ◽  
Gloria McCormick ◽  
Sergio Giralt ◽  
Peter Thall ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Mononuclear Cells ◽  
Methylation Status ◽  
Conditioning Regimen ◽  
Surrogate Marker ◽  
Dose Schedule ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Post Transplant

Abstract Background: Relapse is the most frequent cause of treatment failure after allo-SCT in patients (pts) with AML or MDS. Median time to relapse after reduced-intensity allo-SCT is 3–5 months, indicating that if post-transplant interventions are to be proposed, they have to be implemented early. 5-AC is a DNA hypomethylating agent that may induce leukemic cell differentiation and increased immunogenicity, therefore potentially increasing the graft-versus-leukemia effect. Furthermore, lower doses are likely to be better tolerated after allo-SCT and to be as effective as larger doses in inducing hypomethylation. We hypothesized that 5-AC after allo-SCT will result in lower relapse rates, and designed a phase I clinical trial to determine the safest dose and schedule combination of 5-AC used as maintenance therapy after allo-SCT in pts with AML or MDS. Methods: Pts with AML or high-risk MDS not in first remission are eligible. Donors are HLA-compatible related or unrelated. Conditioning regimen is gemtuzumab ozogamicin 2 mg/m2 (day -12), fludarabine, and melphalan 140 mg/m2. GVHD prophylaxis is tacrolimus and mini-methotrexate. ATG is administered to recipients of unrelated donor transplants. Three doses of 5-AC are to be studied: 8, 16, and 24 mg/m2 daily × 5 starting on day 42 post transplant. Four schedules consisting of 1, 2, 3 or 4 28-day courses of 5-AC are being explored for a total of 3×4 = 12 dose-schedule combinations. The continual reassessment method with toxicity probabilities is used to determine the safest dose schedule combination. Results: Twelve pts were evaluable. Median age was 55.5 years (range 25–66). Eight pts had AML and 4 had MDS. At the time of the transplant 4 pts were in remission and 8 had refractory disease. Donors were HLA compatible related (n=7) and unrelated (n=5). Based on the Bayesian model, 3 pts (25 %) were assigned to 8 mg/m2 × 1 cycle, 2 pts (16%) to 8 mg/m2× 2 cycles, 2 (16%) to 8 mg/m2× 3 cycles and 3 to 16 mg/m2×3 cycles. All evaluable pts have received the assigned 5AC doses, and there has been no major drug-related toxicity (at 8 or 16 mg/m2). Two pts died before receiving 5-AC due to bleeding (n=1, in CR) and bacterial sepsis (n=1) post allo-SCT. With a median follow up of 5 months (2–9) after allo-SCT, none of the pts has relapsed and no drug related induction of GVHD has been observed. All pts were 100% donor chimeras at start of 5AC. To assess the DNA hypomethylating effect of 5-AC, the methylation status of long interspersed nuclear elements (LINE) was analyzed by pyrosequencing and used as a surrogate marker of global DNA methylation in mononuclear cells of 7 patients that have completed 1 cycle at the dose of 8 mg/m2. Mean LINE methylation pretreatment was 64.9%(±5), while it was 60.7%(±2.5) by day 5 (p=0.06) (last day of 5-AC administration), returning to baseline by day 1 of the next cycle. Analysis of gene specific methylation is ongoing. Conclusions: At the dose of 8 mg/m2 5AC is well tolerated and may produce detectable levels of hypomethylation. It is unknown if this effect will translate in reduced relapse rate or if higher doses will be as well tolerated.

Stem Cell Transplantation in Elderly Patients with Acute Lymphoblastic Leukemia (ALL) in First Complete Remission (CR1).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1966-1966
Author(s):  
Renate Arnold ◽  
Dietrich Beelen ◽  
Martin Bornhaeuser ◽  
Donald Bunjes ◽  
Juergen Finke ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
High Risk ◽  
Elderly Patients ◽  
Risk Group ◽  
High Risk Group ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Conditioning Regimens ◽  
Very High

Abstract In the German Multicenter ALL studies (GMALL) patients aged >55 years with high risk (B-lineage ALL with WBC at diagnosis >30000, late CR, t (4; 11), complex aberrant karyotype or prae-T or mature T-ALL) or very high risk (Ph+/BCR-ABL+) ALL are increasingly candidates for allogeneic stem cell transplantation (allogeneic SCT with a HLA identical sibling donor, MRD or a matched unrelated donor, MUD) or autologous SCT. Here, we report on 31 elderly patients transplanted within the GMALL studies 06/99 and 07/03. Median age of the patients was 61 years (56–65). 22 patients belonged to the very high risk group (VHR), 8 patients to the high risk group (HR) and 1 patient from the standard risk group (SR) was transplanted because of detection of minimal residual disease.17/31 patients were transplanted from a matched unrelated donor, 9/31 patients from a HLA identical sibling donor and 5/31 patients underwent autologous SCT. Conditioning regimens for MRD SCT were myeloablative (MAC) in 6 patients (TBI 12 Gy and chemotherapy n=2, radioimmunotherapy + chemotherapy n=2, chemotherapy only n=2) and 3 patients received reduced intensity conditioning (RIC).Conditioning regimens for MUD SCT changed over time with an increasing number of RIC in the study 07/03. In total, 7/17 patients received MAC (TBI 12 Gy and chemotherapy n=5, chemotherapy only n=2) and 10/17 patients received RIC. Conditioning regimens in autologous SCT were myeloablative (MAC) in 5/5 patients. Results: After allogeneic MRD SCT 4/9 patients (44%) are alive in CCR (d+ 24, d+ 611, d+ 1721, d+ 2321), 3/9 patients died due to leukemia, 2/9 due to transplant related mortality (TRM). After allogeneic MUD SCT 8/17 patients (46%) are alive in CCR (from d+ 165 to d+ 2176). 1 further patient is alive after re- SCT for treatment of relapse. 7/17 patients died due to TRM and 1 patient died due to relapse. After autologous SCT 2/5 patients are alive in CCR (d+ 1703, d+ 1731), 3/5 died due to relapse. Risk factors for TRM: In allo SCT and MAC 8/13 patients died due to TRM in contrast to 1/13 patients with RIC. In auto SCT none of the patients died due to TRM. Risk factors for relapse: In allogeneic MRD SCT 3/9 patients died due to relapse and 2/17 patients relapsed after MUD SCT. Due to the small number of patients, no difference between MAC and RIC could be found. In autologous SCT 3/5 patients died due to relapse. In conclusion: The study shows that allo MRD but also MUD SCT is very effective in a selected population of elderly ALL patients. Since the survival of elderly patients with chemotherapy only is about 25%, more patients should be encouraged to have a MRD or MUD SCT.

Reduced Intensity Conditioning with Thiotepa and Fludarabine for Allogeneic Transplantation: Evidence for Low Toxicity and Long-Lasting Disease Control in MDS with Low/Intermediate-1 IPSS Score and in AML from MDS in Complete Remission.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3285-3285
Author(s):  
Emilio Paolo Alessandrino ◽  
Luca Malcovati ◽  
Giorgio La Nasa ◽  
Paolo de Fabritiis ◽  
Massimo Bernardi ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Cox Regression ◽  
Risk Group ◽  
Prognostic Score ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Risk Groups ◽  
High Risk Group ◽  
Valvular Stenosis

Abstract This study investigated Thiotepa (TT) and Fludarabine (Fluda) as a preparative regimen for allogeneic peripheral stem cell transplantation in patients with myelodysplastic syndrome (MDS) or acute leukemia from MDS (MDS-AML) older than 50 or with comorbidities contraindicating standard conditioning. Patients were prepared with TT, given over 3 hours as an i.v. infusion at a dose of 10 mg/kg over two days (day -8 and day -7) and Fluda at the dose of 125 mg/m2 i.v. over five days ( from day -7 to day -3). Fresh or cryopreserved allogeneic peripheral stem cells were infused on day 0 or +1. Graft-versus-Host Disease (GvHD) prophylaxis consisted of cyclosporine A (CyA) at the dose of 1.5 mg/kg day as a continuous iv infusion from day -5 until engraftment. The CyA was then administered orally at the dose of 3 mg/kg twice a day. Doses were adjusted to maintain plasma level concentrations between 150–350 mg/dL. From day +60, in the absence of acute GvHD, the CyA was tapered down by 20% every 2 weeks until withdrawal. In addition, patients received methotrexate 10 mg/m2 on day +1, and 8 mg/m2 on days + 3, +6 and +11 after transplantation. At the time of transplantation, patients were classified in two risk groups (low vs high risk) according to IPSS score (low/intermediate-1 vs. intermediate-2/high) for MDS patients, and disease status (CR vs. not CR) for MDS-AML. Kaplan-Meier survival analysis was carried out to compare Overall Survival (OS), Transplant-Related Mortality (TRM) and probability of relapse. Fifty patients (29 males, 21 females) entered the study; the median age was 54 years (range 38–71). Sixteen MDS patients had a low/intermediate 1 score according to the International Prognostic Score System (IPSS), 16 had an intermediate 2/high IPSS score, 18 had MDS-AML. Thirty patients underwent transplantation as front-line therapy, 20 received one or more cycles of chemotherapy before transplant. Among the latter, nine with MDS-AML were in complete remission at the time of their transplant, while four were in a partial remission. The interval from diagnosis to transplantation ranged from 1 to 52 months (median value 11 months). Contraindications to a standard conditioning regimen were liver disease, hypertrophic cardiomyopathy secondary to hypertension or valvular stenosis, cardiac arrhythmia, diabetes mellitus, hypothyroidism, previous CNS bleeding, and a history of sepsis. All but one patient achieved engraftment, with full donor chimerism by day +30. Patients were followed up for a median time of 21 months (range 0.2–87). TRM at 1 and 2 years after transplantation was 25% and 33%; the 5-year probability of relapse was 27%. Twenty-six patients are alive in complete remission, and the 5-year OS is 50%. The 5-year OS was 73% and 28% in low- and high-risk patients respectively (p=0.002). TRM at 1 and 2 years after transplantation was 13% and 21% in the low-risk group and 39% and 45% in the high-risk group (p=0.046); the 5-year probability of relapse was 10% and 50% in the low- and high-risk group respectively (p=0.015). In a multivariate Cox regression, risk group retained a borderline significance (HR=2.6, p=0.07) when adjusted by age at transplantation (p=0.03) and interval from diagnosis to transplant (n.s.). The combination of Thiotepa and Fludarabine is an effective and well-tolerated conditioning regimen in patients with MDS or MDS-AML who are poor candidates for standard myeloablative transplantation, particularly in MDS patients with low/intermediate-1 IPSS score and MDS-AML patients in CR.

A Simple Clinical Prognostic Scoring System for Newly Diagnosed Cytogenetically Normal Acute Myeloid Leukemia: a Retrospective Analysis on 530 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4848-4848
Author(s):  
Michele Malagola ◽  
Crisitina Skert ◽  
Marco Vignetti ◽  
Alfonso Piciocchi ◽  
Giovanni Martinelli ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Regression Coefficient ◽  
Risk Group ◽  
High Risk Group ◽  
Newly Diagnosed ◽  
Training Set ◽  
Secondary Aml ◽  
Induction Regimen ◽  
Validation Set

Abstract Abstract 4848 Objectives: the prognosis of patients with cytogenetically normal acute myeloid leukemia (CN-AML) is highly variable and can be influenced by several clinical and biological variables. Nevertheless, some biological data may be conflicting and difficult to combine with the clinical ones. Methods: in order to propose a simple scoring system, we retrospectively analysed the clinical data of 337 patients newly diagnosed with CN-AMLs, aged less than 65 years, consecutively treated in eleven hematological Italian Centres from 1990 to 2005. Two hundred nineteen patients (65%) received a fludarabine-based induction regimen. All the other patients received a conventional induction regimen, including cytarabine, one anthracycline with or without etoposide. Univariate and multivariate analysis on event free survival and overall survival (EFS and OS) were performed. Patients addressed to allogeneic stem cell transplantation were censored at the time of transplant. Factors found to be significant in univariate analysis were tested in multivariate analysis. A numerical score was derived from the regression coefficients of each independent prognostic variable. The Prognostic Index Score (PIS) for each patient was then calculated by totalling up the score of each independent variable. Patients could thus be stratified into low-risk (score = 0–1), intermediate-risk (score = 2) and high-risk group (score grater than 3). The score obtained in this group of patients (training set) was then tested on 193 patients with newly diagnosed with CN-AMLs, aged less than 65 years, enrolled in the GIMEMA LAM99p clinical trial (validation set). Results: the clinical variables that were independent prognostic factors on EFS in the training set of patients were: age > 50 yrs (regression coefficient: 0.39, HR 1.5, score = 1), secondary AML (regression coefficient: 0.90, HR 2.5, score = 2) and WBC > 20 × 10^9/L (regression coefficient: 0.83, HR 2.3, score = 2). For what concerns the OS, the same variables showed the followings statistical data: age > 50 yrs (regression coefficient: 0.48, HR 1.6, score = 1), secondary AML (regression coefficient: 0.99, HR 2.7, score = 2) and WBC > 20 × 10^ 9/L (regression coefficient: 0.87, HR 2.4, score = 2). In the training set of patients, the median EFS was 22, 12 and 8 months in the low, intermediate and high-risk group (p<0.0001). The median OS was not reached in the low-risk group and was 20 and 10 months in the intermediate and high-risk group (p<0.0001). In the validation set of patients, the median EFS was 66, 16 and 3 months in the low, intermediate and high-risk group (p<0.0001). The median OS was 66, 16 and 4 months in the low, intermediate and high-risk group (p<0.0001). Conclusions: this simple and reproducible prognostic score may be useful for clinical-decision making in newly diagnosed patients with CN-AMLs, aged less than 65 yrs. Moreover, it can be clinically useful when the molecular prognostic markers are lacking (e.g. in emerging laboratories of some developing countries) or give contradictory results. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Identification of two risk groups in childhood acute myelogenous leukemia after therapy intensification in study AML-BFM-83 as compared with study AML-BFM-78. AML-BFM Study Group

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 1932-1940
Author(s):  
U Creutzig ◽  
J Ritter ◽  
G Schellong
Keyword(s):  
High Risk ◽  
Acute Myelogenous Leukemia ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Myelogenous Leukemia ◽  
Induction Treatment ◽  
Granulocytic Differentiation ◽  
Acute Myelogenous ◽  
The Difference

The main difference between the two cooperative studies on therapy of childhood acute myelogenous leukemia AML-BFM-78 and AML-BFM-83 was the addition of an 8-day ADE (cytosine arabinoside, daunorubicin, etoposide) induction treatment in the second study. Due to this intensification, the relapse rate, but not the rate of induction failures, was reduced. The probability of a 6-year event-free survival increased from 38%, SD 4%, in study AML-BFM-78 to 49%, SD 4%, in study AML-BFM-83, P = .08. The improvement of the 6-year event-free interval (EFI) was significant in the second study (61%, SD 4%, versus 47%, SD 5%, P less than .05); it was restricted to the FAB types M1 through M4 (EFI: 67%, SD 5%, versus 45%, SD 5%, P less than .01). The difference in EFI seen in FAB M5 was not statistically significant (EFI: 40%, SD 10%, versus 63%, SD 11%, NS). According to the results of the second study, two different risk groups (low and high) could be identified by combinations of predominantly pretherapeutic parameters. The low risk group, comprising 37% of the patients who achieved complete remission, included the FAB types with granulocytic differentiation and specific additional features: FAB M1 with Auer rods, FAB M2 with white blood cell count of less than 20,000/microL, FAB M3 all patients, and FAB M4 with eosinophilia. The 6-year Kaplan-Meier estimation of EFI is 91%, SD 4%, compared with 42%, SD 6% in the high risk group. In future studies based on the AML-BFM-83 treatment, bone marrow transplantation in first remission should be mandatory only for children of the high risk group.

scholarly journals Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1382-1388 ◽  
Author(s):  
PJ Tutschka ◽  
EA Copelan ◽  
JP Klein
Keyword(s):  
High Risk ◽  
Acute Leukemia ◽  
Marrow Transplantation ◽  
Risk Group ◽  
Chronic Phase ◽  
Length Of Hospital Stay ◽  
High Risk Group ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Standard Risk

Busulfan 16 mg/kg and cyclophosphamide 120 mg/kg were used as conditioning prior to allogeneic marrow transplantation in 50 adult patients with acute nonlymphocytic leukemia (ANLL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML). A standard risk group of 20 patients included those with acute leukemia in remission and CML in chronic phase. A high-risk group of 30 patients included individuals with refractory acute leukemia, acute leukemia in relapse, acute leukemia following preleukemia, and CML in accelerated and blastic phase. Complete remission and sustained complete engraftment were achieved in all evaluable patients. The duration of aplasia was remarkably short (median of 8 days), resulting in a low infection rate during the period of neutropenia, a reduced need for blood product support, and a short length of hospital stay. Three-year actuarial relapse-free survival in both standard-risk (88.9% +/- 10.5%) and high- risk (50.5% +/- 9.6%) groups compares favorably with that reported with total body irradiation (TBI) containing regimens.

Improved Outcome for Patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) with Poor Risk Cytogenetics – Result from An Analysis on 172 Patients Receiving FLAMSA-RIC Conditioning for Allogeneic Stem Cell Transplantatioin (SCT).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1971-1971
Author(s):  
Tim Pfeiffer ◽  
Michael Schleuning ◽  
Matthias Eder ◽  
Marta Krejci ◽  
Karin Kolbe ◽  
...  
Keyword(s):  
Cox Regression ◽  
De Novo ◽  
Conditioning Regimen ◽  
Chromosome 7 ◽  
Published Data ◽  
Unrelated Donor ◽  
Complex Karyotype ◽  
Chromosome 5 ◽  
Secondary Aml ◽  
Poor Risk

Abstract To improve the results of allogeneic SCT for high-risk AML and MDS, the FLAMSA-RIC conditioning regimen for allogeneic SCT combines cytoreductive chemotherapy (fludarabine, HD AraC, amsacrine), followed three days later by reduced intensity conditioning (4Gy TBI/EDX). Since in particular patients with an unfavorable karyotype seemed to benefit from this approach (Schmid et al., JCO, 2005), we analysed the outcome of 172 patients with poor risk cytogenetics according to NCCN criteria, who had been allografted following FLAMSA-RIC conditioning in 11 European centres between 1999 and 2008. Median time from diagnosis to transplantation was 5 months. Donors were matched siblings, matched unrelated, or mismatched unrelated donors in 34%, 47%, and 19%. Patients suffered from progressive MDS (10%), de novo AML (47.5%), or secondary AML (43.5%). SCT was performed upfront, after primary induction failure, in CR1 and in relapsed disease in 17%, 33%, 22% and 28% of patients, respectively. Median patient age was 53 (18–71) years. 95 patients (56%) had a complex aberrant karyotype, 55 and 65 had abnormalities of chromosome 5 (−5/5q-) and 7 (−7/7q-), respectively. After a median follow up of 20 months, overall survival (OS) at 2 and 4 years was 46.4% and 40.5%, the respective leukemia-free survival was 37.7% and 32.0%. Causes of death were leukemia in 30%, and non-relapse mortality in 21%. Encouraging results were observed in patients with chromosome 7 aberrations or with a complex karyotype leukemia (4y OS=49.3% and 40.3%). In contrast, results were inferior in patients with chromosome 5 aberrations (4y OS=30%), mainly due to an increased rate of leukemia-associated death (p=.008). Patiens with MDS, who received allogeneic SCT as first line treatment, achieved a 4y OS of 80% despite unfavorable cytogenetics. Unlike, patients with secondary AML after MDS had an inferior outcome (4y OS=28%, p=.018). In a Cox regression model, a stage of remission at transplantation, a 8/8 or 10/10 matched family or unrelated donor, and lack of monosomy 5 or deletion 5q were associated with superior OS (p=.025, .05, and .05). In conclusion, allogeneic SCT following the FLAMSA-RIC regimen is a highly effective treatment for MDS and AML with unfavorable karyotype, comparing favourably with published data. In MDS, SCT should be performed before transformation into sAML. Long term remission is achieved in a substantial percentage of patients with complex karyotype disease and aberrations of chromosome 7. Aberrations of chromosome 5 may require alternative or additive strategies.

Sign in / Sign up

Export Citation Format

Share Document