scholarly journals T Cell–Depleted Stem Cell Transplantation for Adults with High-Risk Acute Lymphoblastic Leukemia: Long-Term Survival for Patients in First Complete Remission with a Decreased Risk of Graft-versus-Host Disease

2013 ◽  
Vol 19 (2) ◽  
pp. 208-213 ◽  
Author(s):  
Jenna D. Goldberg ◽  
Alex Linker ◽  
Deborah Kuk ◽  
Ravin Ratan ◽  
Joseph Jurcic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Term Survival ◽  
Graft Versus Host ◽  
First Complete Remission

A High Long-Term Survival Were Produced by Early Sequential Intensive Consolidation Chemotherapy Followed by Autologous Stem Cell Transplantation in First Complete Remission in Patients with Adult Acute Lymphoblastic Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3324-3324
Author(s):  
Dehui Zou ◽  
Lugui Qiu ◽  
Yenan Li ◽  
Yaozhong Zhao ◽  
Mingzhe Han ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Consolidation Chemotherapy ◽  
Term Survival ◽  
First Complete Remission

Abstract Objective: To investigate the efficiency of our designed protocol with early sequential intensive consolidation chemotherapy followed by autologous stem cell transplantation (ASCT) in first complete remission (CR1)on adult acute lymphoblastic leukemia (ALL) patients who lack of matched sibling donors. Methods: The ALL patients were given a median 4 intensive/ consolidation therapy courses including high-dose of methotrexate, cytarabine and/or cyclophosphamide in CR1, followed by ASCT with total body irradiation (TBI)-based conditioning regimen. A 1 to 1.5 year maintenance chemotherapy with 6-mercaptopurine, methotrexate and vincristine-prednisone in combination with interleukin-2/IFN-α immunotherapy were administered after adequate hematological recovery. Results: A total of 83 patients were enrolled in this study. 78 patients reconstituted hematopoiesis except 5 patients died of early toxicity. By a median 47(3– 218) months follow-up after ASCT, the 5-year probabilities of leukemia free survival (LFS) and overall survival (OS) were 53.2%±5.9% and 54.4%±5.8%, respectively. The 5-year cumulative relapse rate (RR) was 35.7%±6.1%, and no patients relapsed more than 3 years after transplantation. According to the adverse features, age ≥35 years, WBC >30×109/L for B-cell ALL or >100×109/L for T-ALL, Pro-B and early T immunotyping, more than 4 weeks to attain remission, and high-risk karyotypes including t(9;22)/BCRABL, t(4;11)/ALL1-AF4 or t(1;19)/E2A-PBX1, the patients were identified in 3 prognostic risk groups of standard (24, 29.0%), intermediate(32, 38.5%), and high(27, 32.5%) with 0, 1, 2 or high-risk karyotypes adverse features, respectively. The 5-year probabilities of DFS were 80.36%±9.0%, 59.39%±9.2% and 24.78%±8.9% in these 3 group s, respectively. While, the 5-year cumulative incidences of relapse was 16.7%,37.5% and 70.4%, respectively.. The standard and intermediate -risk groups had significantly better OS and LFS than the high-risk group. Conclusion: Theses results indicated our designed protocol with early sequential intensive consolidation chemotherapy followed by autologous stem cell transplantation (ASCT) in first complete remission (CR1) could produced a relatively high log-term survival in standard and intermediate-risk group of adult ALL patients.

Allogeneic Stem Cell Transplantation Should Be Performed in First Complete Remission in Adults with Acute Lymphoblastic Leukemia; Strong Antileukemic Activity of Chronic Graft-Versus-Host Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2992-2992
Author(s):  
Seok Lee ◽  
Byung-Shik Cho ◽  
Sung-Yong Kim ◽  
Ki-Seong Eom ◽  
Yoo-Jin Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Graft Versus Host ◽  
First Complete Remission

Abstract Purpose: The role of allogeneic stem cell transplantation (SCT) for adult acute lymphoblastic leukemia (ALL) remains unclear because interpretation of transplantation outcome is complicated by the criteria used to select patients for transplantation and by the relatively small number of patients studied. Moreover, whether SCT from an unrelated donor could be a treatment option of equal value in a case lacking a compatible related donor remains controversial. The aim of the present study was to determine the graft-versus-leukemia (GVL) effect and risk factors affecting outcome of 218 adults with ALL who received allogeneic SCT during the last 10 years (1995 to 2004). Patients and Methods: The study population was 218 consecutive adults receiving an allogeneic SCT from matched sibling (n=162) or unrelated (n=56; 40 matched, 16 mismatched) donors at the Catholic Hematopoietic Stem Cell Transplantation Center in Korea. Their median age was 30 years (range, 15–61 years). One hundred eighty-three (83.9%) patients had high-risk criteria, and of these, 69 (31.7%) had t(9;22)/BCR-ABL and 7 (3.2%) had t(4;11)/MLL-AF4. One hundred sixty-five patients (75.7%) were transplanted in first complete remission (CR1); 23 (10.5%) in CR2; and 30 (13.8%) were resistant to chemotherapy before transplantation. Most patients (n=206, 94.5%) received a preparative treatment of total body irradiation (TBI)-containing regimen (TBI/cyclophosphamide for CR1, TBI/cytarabine/melphalan for >CR1). Graft-versus-host disease (GVHD) prophylaxis was attempted by administering calcineurin inhibitor (cyclosporine for sibling, tacrolimus for unrelated) plus methotrexate. Results: With a median follow-up of 52 months (range, 15+ to 130+ months) after SCT, the 5-year probability of disease-free survival (DFS) was 51.3%±3.5% for all patients; 62.4%±4.3% for patients in CR1; and 11.3%±4.4% for patients in >CR1 at transplantation. There was no difference in DFS for sibling and unrelated transplant patients in CR1 (65.2%±4.3% v 62.3%±8.0%). Multivariate Cox regression analysis showed that the most powerful predictive factor affecting relapse and DFS was disease status at transplantation (CR1 v >CR1, p<0.001). The presence of chronic GVHD was also found to be significantly associated with favorable outcome (p<0.001). Conclusion: Our data in combination with recent studies suggest that matched related or unrelated allogeneic SCT should be performed in CR1 in adults with ALL. Further studies to develop treatment strategies to reduce leukemic cell burden and to enhance GVL effect are needed. The indications for allogeneic SCT also should be continuously evaluated.

Allogeneic Hematopoietic Stem-Cell Transplantation in Adult Acute Lymphoblastic Leukemia: Better Outcome in Transplantation during First Complete Remission and with Myeloablative Conditioning

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3295-3295
Author(s):  
Avichai Shimoni ◽  
Avital Rand ◽  
Izhar Hardan ◽  
Noga Shem-Tov ◽  
Anfisa Stanevsky ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Refractory Disease ◽  
Myeloablative Conditioning ◽  
Standard Risk ◽  
First Complete Remission

Abstract Allogeneic stem-cell transplantation (SCT) is potentially curative therapy in acute lymphoblastic leukemia (ALL). However, the timing of SCT during disease course and the prognostic factors for outcome are still under debate. We retrospectively analyzed all allogeneic transplants given for ALL over a 7-year period in a single institution. During this period we have used a uniform policy according to the GMALL protocols. Patients determined to be at high-risk at presentation were transplanted in the first complete remission (CR1) most often after first consolidation. Patients at standard risk at presentation were only transplanted after failure of induction or at relapse. Patients were transplanted from the best available donor and sibling donor availability was not a pre-request in any setting when referring to SCT. Patients considered eligible for myeloablative conditioning were given high-dose cyclophosphamide and TBI (12 cGy in 6 fractions). Patients considered non-eligible for myeloablative conditioning were given a reduced-intensity conditioning regimen (RIC) consisting of fludarabine and melphalan (total 140/m2). Patients with unrelated donors were also given ATG during conditioning. The study group included 81 patients, median age 40 years (range, 17–65). Immunophenotyping was B (n=31), T (n=48) and NK (n=2). Twenty-nine patients had high-risk cytogenetics [Ph+-24, t(4;11)-4, t(1;19)-1]. The donor was an HLA-matched sibling (n=48), matched unrelated (n=23), haplo-identical relative (n=8) and double umbilical cord blood (n=2). At the time of SCT, 36 patients were in high-risk CR1 (by the GMALL criteria), 12 were in CR after salvage therapy given for induction failure (CRIF), 13 patients were in CR2, and 20 patients were given SCT during active chemo-refractory disease. With a median follow-up of 27 months (range, 1–79), 31 patients are alive and 50 died (31 relapse, 19 non-relapse causes). Five patients are alive after relapse, all with isolated extra-medullary relapse (CNS-2, breast-1, bone-1, mediastinum-1). All patients with systemic relapse died of their disease. Overall and disease-free survival at 3 years were 33% (95CI, 22–44%) and 26% (95CI, 15–37%), respectively. The status of disease at SCT was the most important factor predicting for OS; the 3-year OS rates are 52%, 28%, 28% and 5% for patients transplanted in CR1, CRIF, CR2 and active disease respectively (p=0.0004). Donor type was also predicting for outcome in the univariable analysis; 3-year OS was 35%, 42% and 10% after sibling, unrelated and alternative donor transplants, respectively (p=0.04). OS rates after myeloablative conditioning and RIC were 37% and 20%, respectively (p=0.02). High-risk cytogenetics was not a risk factor for survival. Ph+ and Ph− patients had an OS of 38% and 30%, respectively, and when only analyzing patients in CR1, 48% and 53%, respectively (p=NS). Age, gender and immunophenotype were also not predicting for OS. Multivariable analysis identified two factors; SCT during CR1 was a favorable factor with HR of 0.3 (0.1–0.5, P=0.0005), while SCT with RIC was an adverse factor, HR 2.7 (1.4–5.2, P=0.004). Patients transplanted in high-risk CR1 with myeloablative conditioning had a 3-year OS of 55% (95CI, 36–75). In conclusion, best results are achieved in ALL in SCT during CR1. One can extrapolate that even better results may be expected in SCT in standard-risk ALL in CR1. Outcome after relapse and especially in chemo-refractory disease is poorer. RIC should only be used when there is an absolute contraindication for standard myeloablative conditioning.

Outcome of Allogeneic Hematopoietic Stem-Cell Transplantation in Adult Patients With Acute Lymphoblastic Leukemia: No Difference in Related Compared With Unrelated Transplant in First Complete Remission

2004 ◽  
Vol 22 (14) ◽  
pp. 2816-2825 ◽  
Author(s):  
Michael G. Kiehl ◽  
Ludwig Kraut ◽  
Rainer Schwerdtfeger ◽  
Bernd Hertenstein ◽  
Mats Remberger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Hematopoietic Stem ◽  
First Complete Remission

Purpose The role of unrelated allogeneic stem-cell transplantation in acute lymphoblastic leukemia (ALL) patients is still not clear, and only limited data are available from the literature. We analyzed factors affecting clinical outcome of ALL patients receiving a related or unrelated stem-cell graft from matched donors. Patients and Methods The total study population was 264 adult patients receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone marrow transplantation centers between 1990 and 2002. Of these, 221 patients receiving a matched related or unrelated graft were analyzed. One hundred forty-eight patients received transplantation in complete remission; 62 patients were in relapse; and 11 patients were refractory to chemotherapy before transplant. Fifty percent of patients received bone marrow, and 50% received peripheral blood stem cell from a human leukocyte antigen–identical related (n = 103), or matched unrelated (n = 118) donor. Results Disease-free survival (DFS) at 5 years was 28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation), and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an advantage regarding DFS in favor of patients receiving transplantation during their first complete remission (CR) in comparison with patients receiving transplantation in or after second CR (P = .014) or who relapsed (P < .001). We observed a clear trend toward improved survival in favor of B-lineage ALL patients compared with T-lineage ALL patients (P = .052), and Philadelphia chromosome–positive patients had no poorer outcome than Philadelphia chromosome–negative patients. Total-body irradiation–based conditioning improved DFS in comparison with busulfan (P = .041). Conclusion Myeloablative matched related or matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL patients should be performed in first CR.

scholarly journals Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Blood ◽  
2015 ◽  
Vol 125 (16) ◽  
pp. 2486-2496 ◽  
Author(s):  
Nathalie Dhédin ◽  
Anne Huynh ◽  
Sébastien Maury ◽  
Reza Tabrizi ◽  
Kheira Beldjord ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Key Points ◽  
First Complete Remission

Key Points SCT in first complete remission is associated with 69.5% 3-year overall survival in high-risk ALL adult patients treated with intensified pediatric-like protocol. Poor early MRD response is a powerful tool to select patients who may benefit from SCT in first complete remission.

Prognostic Impact of Different High Risk Features in Allogeneic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in First Complete Remission.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2303-2303
Author(s):  
Theis Terwey ◽  
Philipp Hemmati ◽  
Gero Massenkeil ◽  
Bernd Dörken ◽  
Renate Arnold
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Prognostic Impact ◽  
Very High ◽  
First Complete Remission

Abstract Abstract 2303 Poster Board II-280 Introduction: In acute lymphoblastic leukemia (ALL) specific clinical and biological features confer high relapse risk and inferior overall survival (OS) after treatment with conventional chemotherapy alone. The differential prognostic impact of these high risk features after treatment with allogeneic hematopoietic stem cell transplantation (HCT) has not been well studied. Patients and Methods: 79 adult ALL patients in first complete remission (CR) received allogeneic HCT at our center between 1995 and 2008. All patients were high or very high risk according to German Multicenter Study Group for Adult ALL (GMALL) criteria. Median age was 36 years (range: 17-68). Patients received high-dose conditioning consisting of 12 Gy total body irradiation ± etoposide ± cyclophosphamide (n=69, 87%) or reduced intensity conditioning (RIC) consisting of fludarabine/busulfan/ATG (n=10, 13%) and HSCT from related (n=34, 43%) or unrelated (n=45, 57%) donors. Bone marrow (n=17, 22%) or peripheral blood stem cells (n=62, 78%) were given. Graft-versus-host-disease prophylaxis was CSA/MTX for high-dose conditioning or CSA/MMF for RIC. Results: Patients were classified as high risk or very high risk due to Philadelphia chromosome-positive disease (Ph+) (n=30, 38%), leukocytosis>30/nl at diagnosis in B-ALL (n=25, 23%), late response to induction therapy in B-ALL (>week 4) (n=13, 16%), early or mature T-ALL (n=13, 16%), pro-B-ALL/t(4;11) (n=8, 10%), persistence of minimal residual disease (MRD) (>week 16) (n=8, 10%) or complex aberrant karyotype (n=6, 8%). 57 patients (72%) presented with one high risk feature, whereas 20 patients (25%) and 2 patients (3%) presented with two or three features, respectively. Currently, after a median follow-up of 56 months (7-169) 49 patients (62%) remain alive. Projected OS of the whole cohort at 1, 2 and 5 years was 78%, 70% and 55% and leukemia-free survival was 77%, 66% and 55%. Cumulative incidence of non-relapse mortality (NRM) and relapse mortality (RM) at 5 years was 23% and 18%, respectively. In multivariate Cox regression analysis, a non-significant trend for inferior OS was seen for patients with early or mature T-ALL (hazard ratio (HR): 2.03 (95%CI: 0.92-4.52), p=0.082), whereas no differential effect on OS, NRM or RM was seen for any other high risk feature (Table 1). In additional analyses, inferior OS (HR 1.81 (95%CI: 1.02-3.29), p=0.043) and increased RM (HR 2.17 (95%CI 1.16-4.05), p=0.015) was observed for patients with more than one high risk feature. Conclusions: In summary, this single center study on allogeneic HCT in high risk ALL found a negative prognostic trend for early or mature T cell immunophenotype. No differential prognostic impact on OS, NRM and RM was seen for other high risk features as defined by GMALL criteria, however this conclusion is limited by the low patient number in some of the subgroups. Overall survival for the whole cohort was 55% at 5 years, with inferior OS and higher RM being observed in patients with more than one high risk feature. Disclosures: No relevant conflicts of interest to declare.

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