Molecular Relapse of Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation Can Be Successfully Treated with Donor Lymphocyte Infusions.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5122-5122
Author(s):  
Alida Dominietto ◽  
Anna Maria Raiola ◽  
Raffaella Grasso ◽  
Anna Garuti ◽  
Carmen di Grazia ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Donor Lymphocyte Infusions

Abstract Background. Hematologic relapse is seen in 20–40% of adult acute lymphoblastic leukemia (ALL) patients undergoing an allogeneic hematopoietic stem cell transplant (HSCT) and is usually non responsive to donor lymphocyte infusions (DLI). This has suggested a lack of graft vs leukemia effect (GvL) in ALL patients. It is currently possible to monitor minimal residual disease (MRD) post-HSCT and this may allow to identify patients at high risk of hematological relapse. Objectives. To monitor MRD in B-ALL patients post-HSCT and to treat MRD positive patients with DLI. Patients and Methods. MRD was evaluated on bone marrow samples using nested polymerase chain reaction (PCR) and real time PCR (RT-PCR) assay to analyze respectively IgH VDJ and BCR-ABL gene rearrangement. Molecular positivity/relapse was defined with two consecutive positive PCR assays. MRD monitoring was performed in 28 patients grafted from an HLA-identical sibling (n=19), family mismatched related donor (n=2) or matched unrelated donor (n=7). Median follow-up was 47 months (range 5–163). Sixteen patients (57%) were in early disease phase at the time of transplant. Results. We identified 3 groups of patients. A) 14 patients (50%) had no evidence of MRD after HSCT. B) 6 (21%) had a positive MRD and received escalating dose DLI, within 60 days and C) 8 (29%) had a positive MRD, but did not received DLI, because not available or because of an early hematological relapse. Median time from HSCT to molecular relapse was 139 days (range 46–1048). The median follow up was 1385 days (144 – 4877). Median number of infused CD3+ cells was 0.6x10^7/Kg of recipient body weight (range 0.01–7). Hematological relapse was seen in 0%, 0% and 88% respectively of group A,B,C (p=0.0001) and disease-free survival (DFS) was 100% , 67% , 12% (p=0.0001). Conclusions. This study shows that (1) MRD monitoring of ALL patients post-transplant identifies patients at high risk of hematologic relapse and (2) that treatment with DLI, on the basis of MRD positivity, significantly reduces the risk of leukemia relapse and may improve DFS. These data also confirm the existence of a GvL effect, previously shown in this disease (Weiden et.al NEJM, 300, 1068; 1979).

Risk Factors for Outcome after Haploidentical Hematopoietic Stem Cell Transplant in Children with Very High Risk Acute Lymphoblastic Leukemia: Impact of Centre Experience. A Survey on Behalf of the ALWP and PDWP of the EBMT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 438-438 ◽  
Author(s):  
Thomas Klingebiel ◽  
Jacqueline Cornish ◽  
Myriam Labopin ◽  
Franco Locatelli ◽  
Adriana Balduzzi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Alternative Option ◽  
Significant Difference ◽  
Very High

Abstract In the absence of an HLA identical donor, T-cell depleted haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) is an alternative option to treat children with very high risk acute lymphoblastic leukemia (ALL). However, little data is available in children. We have analyzed 118 children (≤16 years old) with ALL transplanted with a myeloablative Haplo-HSCT from 1995 to 2004 in Europe. Only transplants with 2 or more HLA disparities out of 6 (A, B and DRB1) were included. The median age was 8.5 years and median follow-up 56 months (8–116). At transplant, 21 (18%) were in CR1, 72 (61%) in CR2 or CR3 and 25 (21%) in more advanced phase. The 3-year leukemia free survival was 32±10%, 28±5% and 0%, respectively. Therefore we restricted the analysis to patients in remission (n=93) transplanted in 30 EBMT centers. Thirty-four (37%) patients were treated in centres performing more than 10 Haplo-HSCT in the study period (3 centres). The median age of recipient and donor was 8.7 and 37 years, respectively. Fifty four (65%) received a full Haplo-HSCT and 95% of the donors were parental. Twenty seven (29%) had t(9;21) or t(4;11). The majority of patients did not receive drugs for GVHD prophylaxis, ATG/ALG was used in conditioning in 74%, and 73% received TBI. The Clinimacs® device was used in 74% of selections. The median number of CD34+ cells infused was 12.8 106/Kg. Cumulative incidence with competing risk and KM estimates were used to calculate outcome probabilities. The median days of neutrophil recovery was 15 days (8–55) and 90% of patients had signs of engraftment. Acute GVHD II–IV was observed in 24% of the patients. In univariate analysis for LFS there was a trend towards better results for patients receiving higher CD34 cell dose (p=0.08) and a significant difference for patients transplanted in centres performing more Haplo-HSCT (49% versus 17%, p=0.002). Relapse incidence (RI) and non relapse mortality NRM) tended to be different between the experienced and less experienced centres. In less experienced centres NRM was 41% vs 27% (p=0.13) and RI 41% vs. 24% (p=0.10). There were patient, donor and transplant related differences between less and more experienced centres, specifically related to donor sex, Philadelphia positivity, year of transplantation, use of TBI, ATG and DLI and previous autograft. In conclusion, Haplo-HSCT is an alternative option to treat children with very high risk ALL in the absence of HLA identical donor. Centres with more experience have better LFS.

Results of T Cell Depleted (TCD) Myeloablative Hematopoietic Stem Cell Transplants (HSCT) in Patients with Hematologic Malignancies ≥ 55 yrs of Age.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3660-3660
Author(s):  
Ann A. Jakubowski ◽  
Esperanza B. Papadopoulos ◽  
Hugo R. Castro-Malaspina ◽  
Katharine Hsu ◽  
Miguel-Angel Perales ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
High Risk Patient ◽  
Disease Status ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Conditioning Regimens ◽  
Good Risk

Abstract Allogeneic HSCT remains the only curative therapy for many patients(pts) with hematologic diseases. Studies have suggested that older pts experience greater toxicity from the intensive chemo-radiotherapy used in myeloablative conditioning regimens. As a consequence, many older pts are now offered non-myeloablative transplants (NMAT) for malignant conditions where a graft vs. tumor effect (GvT) is expected to provide the antitumor effect in place of the chemo-radiotherapy. Unfortunately, graft vs. host disease (GvHD) remains a common occurrence after conventional transplants, occurring more frequently in older pts and unrelated donor transplant recipients, resulting in significant morbidity and mortality. Furthermore, the efficacy of NMAT is limited by the disease status at time of transplant and by the susceptibility of the hematologic disease to a GvT effect. TCD of hematopoietic stem cell grafts offers an alternative to older pts, in particular those requiring unrelated donor transplants (URD), with the advantage of a reduced incidence of GvHD. From 1995–2005, 57 patients ≥55 yrs received myeloablative TCD transplants at our institution. The median age was 58.2 (range 55–69.2) yrs. Stem cell sources were TCD bone marrow, PBSC or both. Thirty-seven received transplants from related donors (RD), including two mismatched, and 20 received transplants from unrelated donors (URD), 9 of whom were mismatched. In addition to their advanced age, many of these pts were considered high risk based on the status of disease, HLA mismatch, and history of previous therapy. Twenty-three pts were considered “good risk” by disease status (CML-CP1, AML-CR1, CR2) and 34 pts were considered poor risk (>CML-CP1, >AML CR2, MDS, NHL, >ALL CR1, ABL.) BM was TCD by soybean agglutination followed by sheep red blood cell rosetting (E), and PBSCs by CD34+ selection and E-rosetting. Conditioning regimens included total body irradiation (TBI) in addition to thiotepa and cyclophosphamide, or thiotepa and fludarabine. The non-TBI preparative regimen consisted of busulphan, melphalan and fludarabine. Anti-thymocyte globulin was used as rejection prophylaxis for all TCD transplants until 2001 when it was eliminated from the TBI containing regimen for matched RD transplants. A total of 25 pts (15 matched RD and 10 URD, 6 of whom were mismatched) are alive following TCD transplants with a median follow up of 24 mos. for RDs and 12 for URDs. Of the survivors, 2/10 URD and 14/15 RD recipients received TBI containing regimens based on the triage system at our center. Three pts with CML-CP1, one with CML-acc and one with AML-CR1 showed evidence of minimal residual disease, received donor leukocyte infusions and subsequently achieved longterm continued CR. The incidence of post-transplant GvHD was low despite the high number of mismatched URD transplants - 1 Grade IV (RD), 2 Grade 3 and 1 Grade 1 (URD). The 100 day mortality was 15%. Overall and current disease free survival for ‘good risk’ patients based on disease status is 58% for RD and 60% for URD. Although longer follow up is necessary to confirm these results, the promising DFS rates in association with a low incidence of GvHD in this older and relatively high risk patient population support further investigation of myeloablative TCD HSCT in these patients.

A Single-Center Retrospective Analysis of a Pediatric Salvage Chemotherapy Regimen for Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4919-4919
Author(s):  
Ben A. Blomberg ◽  
Hendrik W. Van Deventer ◽  
Stuart Gold ◽  
Katarzyna Joanna Jamieson ◽  
Joshua F. Zeidner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Salvage Chemotherapy ◽  
Adult Patients ◽  
Intrathecal Methotrexate ◽  
Cell Transplant ◽  
Single Center ◽  
Hematopoietic Stem

Abstract Background: Relapsed or refractory acute lymphoblastic leukemia (ALL) remains challenging to treat with an extremely poor prognosis. Salvage chemotherapy regimens can achieve complete remission (CR) rates of 30-50%, but CRs are not durable without hematopoietic stem cell transplant (HSCT). Outcomes in untreated adolescents and young adults have improved with the use of pediatric chemotherapy regimens, but data on the use of pediatric chemotherapy regimens in relapsed/refractory adult ALL is lacking. We chose to retrospectively examine the outcomes of adult patients with relapsed ALL at our institution treated with the CCG-1941 pediatric salvage protocol (Gaynon PS, et al. J Clin Oncol 2006). Methods: We conducted a single-center retrospective cohort study of patients aged 18 and older with relapsed/refractory ALL who were treated with the CCG-1941 protocol. Patients received induction with vincristine, dexamethasone, ifosfamide, etoposide, PEG-asparaginase, and methotrexate, as well as intrathecal methotrexate, cytarabine, and hydrocortisone prophylaxis, followed by intensification and continuation phases. This regimen was offered to relapsed/refractory patients who, in the judgement of treating physician, were likely to tolerate multiagent chemotherapy. All adult patients who received this regimen between 2006 and 2015 were included in the analysis. Outcomes of interest were: the CR rate, duration of remission (DOR), toxicity, 30-day mortality, and the rate of patients undergoing HSCT. Results: Between January 2006 and April 2015, 15 patients aged 20-54 (median 31) with first relapse (n=12) or refractory (n=3) ALL were treated with the CCG-1941 regimen. Baseline patient characteristics are described in the Table 1. Seven patients (47%) had alterations to the induction protocol. The majority of these modifications were reduction or omission of PEG-asparaginase or vincristine. All patients experienced infectious complications, most commonly neutropenic fever (n= 12, 80%, 95% CI 52-96). There was one death due to infection, which occurred during an intensification phase. Two patients had grade 3 pancreatitis and two patients had hemorrhage (one grade 2, and one grade 5). 30-day mortality was 7% (95% CI 0-32) due to one fatal intracranial hemorrhage. Median length of hospitalization for induction was 28 days (range 10-61). Twelve patients (80%, 95% CI 52-96) achieved CR, and six of these patients received 1-2 cycles of intensification or continuation. Among the remaining 6 CR patients, one proceeded immediately to HSCT, two received other consolidation, two had early relapse, and one was lost to follow up. Six patients proceeded directly to HSCT, and one more underwent HSCT after receiving subsequent therapies for relapsed disease. The DOR was 81% at 6 months, 54% at 12 months, 36% at 18+ months and 18% at 24 months. One patient has been followed for 63 months and has not recurred. Median follow-up for survivors was 16 months (range 3.6-63). Conclusions: The CCG-1941 regimen appears to be tolerable and efficacious in adult patients with relapsed/refractory ALL. This regimen has been previously reported only in children. Despite the regimen's toxicities, a substantial proportion of patients underwent subsequent stem cell transplantation. Such salvage therapies remain important options for patients with T-ALL and for those B-ALL patients who are not candidates for, or who have failed phenotype-specific immunotherapies. Further prospective, multicenter study is warranted for use of pediatric salvage regimens in the adult patient population. Disclosures Foster: Celgene: Research Funding.

Inotuzumab Ozogamicin (IO) Is An Effective Salvage Therapy That Allows for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Remission in Patients with Advanced Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3102-3102
Author(s):  
Partow Kebriaei ◽  
Kaci Wilhelm ◽  
Farhad Ravandi ◽  
Rima M. Saliba ◽  
Marcos De Lima ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Salvage Therapy ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Inotuzumab Ozogamicin ◽  
Hematopoietic Stem ◽  
Conditioning Regimens

Abstract Abstract 3102 No highly effective salvage therapy exists for patients with relapsed acute lymphoblastic leukemia (ALL). Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody attached to calicheamycin and targets B lymphocytes in early stages of development. A 56% overall response rate was noted in a Phase I study of single agent IO in patients with refractory ALL (Jabbour ASCO 2011), enabling subsequent transplant in remission in a relatively large number of patients. Of note, in the year prior to the availability of IO, we consulted on 13 patients will ALL beyond second remission and transplanted 5 (38%), and after the availability of IO, we consulted on 41 patients and transplanted 27 (67%). Methods: We describe our findings in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) following treatment with IO between June 2010 and May 2011. IO was administered at 1.8 mg/m2 IV every 3 weeks. Results: 19 patients with median age 32 years (range 5–60) received an allogeneic matched sibling (n=6), matched unrelated donor (n=8), mismatched unrelated donor (n=4), or cord blood HSCT (n=1) in complete remission (CR) (n=2), CR without platelet recovery (n=14), and active disease (n=3); 10 patients were MRD negative at time of HSCT as determined by multiparameter flow cytometry. Patients had received 2 (n=3), 3 (n=9), 4 (n=4), 5 (n=2), or 6 (n=1) lines of salvage therapy prior to HSCT, including 3 patients who had received a prior allogeneic HSCT; IO was the last agent in 17 patients (2 patients refractory to IO received other therapy prior to HSCT). Patients received 1 (n=1), 2 (n=9), 3 (n=6), 4 (n=2), or 5 (n=1) courses of IO a median of 35 days (range 18–69) prior to transplant conditioning with busulfan (Bu) and colafarabine (Clo) (n=8), BuClo+ thiotepa (TT) (n=4), fludarabine (Flu) and melphalan (Mel) (n=1), FluMelTT (n=3), or etoposide and total body irradiation (TBI) (n=3); GVHD prophylaxis was tacrolimus-based for all patients, with post-HSCT cyclophosphamide added for patients receiving mismatched unrelated donors. With a median follow-up of 3 months among surviving patients (0.6–8.2), overall and progression-free survival is 59% at 3 months. There were 11 deaths, 6 from relapse, 4 from multi-organ failure involving VOD, and 1 from pneumonia. Transient liver enzyme elevations were noted in all of the patients, with 26% (n=5) patients developing VOD. The development of VOD was associated with greater lines of prior therapy prior to HSCT (3–5 lines prior salvage therapy, including 2 patients who had a prior allo-HSCT) and more intense transplant conditioning regimens (4 of the 5 patients received BuCloTT or FluMelTT). Conclusions: IO is an effective salvage therapy in patients with advanced ALL, allowing more patients to receive HSCT with encouraging response rates. Longer follow-up is needed to more completely assess disease control. Using reduced intensity HSCT conditioning regimens and avoiding multiple lines of prior therapies may result in less hepatic toxicity. Disclosures: O'Brien: Pfizer: Consultancy. Kantarjian:Pfizer: Research Funding.

Nelarabine-Based Salvage Therapy in Adult Patients with T-Cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma (T-ALL/LL) Relapsing After Allogeneic Stem Cell Transplantation: A French Experience on Behalf of the Group for Research in Adult Lymphoblastic Leukemia (GRAAL),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4095-4095
Author(s):  
Edouard Forcade ◽  
Thibaut Leguay ◽  
Norbert Vey ◽  
Andre Baruchel ◽  
Jacques Delaunay ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
High Risk ◽  
Salvage Therapy ◽  
Acute Gvhd ◽  
Response Rate ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem

Abstract Abstract 4095 Backgroud: The prognosis of patients with T-ALL/LL has been recently re-assessed, based on monitoring of minimal residual disease (MRD) levels and new insights in pathogenesis (NOTCH1 pathway mutations). To date, allogeneic hematopoietic stem cell transplant (HSCT) in first complete remission (CR) remains the standard option in patients identified with a high risk of relapse. In this context, patients relapsing after HSCT represent a very difficult challenge to get a second CR. Nelarabine, a pro-drug of Ara-G, has been associated with a high response rate in relapsing ALL (Gökbuget N et al., Blood 2011), but very few data are available on its efficacy and safety in the post-HSCT setting. Patients: Medical records of 11 T-ALL/LL patients who received nelarabine-based salvage therapy for a relapse after HSCT were retrospectively reviewed. These patients were treated with nelarabine alone (1,5g/m2/day (D) D1, D3, D5, every 28 days) (N=5) or nelarabine associated with hyperfractionated cyclophosphamide (HyperC; N=6). Results: Ten patients had T-ALL and one had T-LL. Median age was 23 years (14–62) at time of diagnosis. Ten patients underwent HSCT in first CR (median time between diagnosis and HSCT: 141 days). HSCT conditioning regimen was myeloablative for 7 patients including Total Body Irradiation for 6 of them (reduced intensity conditioning for 4 patients). Source of stem cells was hematopoietic peripheral blood stem cells in 6 patients, bone marrow in 4 patients and unrelated cord blood in one patient. Four patients received a transplant from an HLA matched sibling donor and 7 from an unrelated donor (HLA-matched 10/10 in 3 patients). GVHD prophylaxis consisted in ciclosporine for all patients, either associated with methotrexate for 8 patients, mycophenolate for 2 patients or alone for one patient. Eight patients presented grade I-II acute GVHD (no patient had grade III-IV). Two patients developed chronic GVHD (1 extensive). Relapse occurred with a median duration of 199 days (119–2099). Six patients were still under immunosuppressive agents, because of slow tapering off or context of GVHD, which was stopped quickly. One patient presented a relapse in the context of cGVHD. Of the 11 patients treated with nelarabine-based salvage therapy, 81% achieved hematological CR within a median delay of 48 days. At one year, disease-free and overall survivals were 56% and 90%, respectively. Eight patients received additional nelarabine consolidation cycles (median, 4 cycles) and 2 CR patients received Donor Lymphocytes Infusion (1 complete molecular CR). One patient presented acute GVHD following nelarabine-based first cycle, requiring immunosuppressive treatment. Main toxicity was neurological (Grade 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events), with 2 patients presenting sensitive neuropathy and cerebellar ataxia. Conclusion: In patients with T-ALL/LL relapsing after allogeneic HSCT, nelarabine-based salvage therapy was well tolerated with 2 neurological complications grade 2 and one acute GVHD. Moreover, this treatment was associated with a very high (81%) response rate with some patients experiencing prolonged remission. Post-HSCT nelarabine maintenance might thus be a valuable option to investigate in high-risk patients, possibly driven by MRD detection. Assessing immune responses in this particular setting could also be of particular interest. Disclosures: Peffault de Latour: Alexion: Consultancy, Research Funding.

The Superiority of Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated Donor Over Chemotherapy As Post-Remission Treatment for Patients with High-Risk Acute Lymphoblastic Leukemia in First Remission

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1986-1986
Author(s):  
Jiong Hu ◽  
han-Bo Dou ◽  
Ling Wang ◽  
Wei Tang
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Relapse Rate ◽  
Lymphoblastic Leukemia ◽  
P Value ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Chemotherapy Group

Abstract Abstract 1986 For adult patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched related donor (MSD) is recommended for standard and high-risk patients. The role of unrelated donor transplantation (URD) is not fully determined. In this single-center retrospective analysis, we included all consecutive adult patients with high-risk ALL in 1st complete remission (CR) without sibling donor between Jan 2007 to June 2012. Overall, 74 patients were included in the analysis in which 32 patients received URD allo-HSCT during 1st CR with busulfan-cyclophophamide preparation regimen and in vivo T cell depletion with anti-T-lymphoglobulin (ATG). The median time from remission to transplantation was 4.5 months (3∼13). Forty-two patients in the chemotherapy group with 1st CR more than 6 months received consolidation chemotherapy alone either due to lack of suitable URD (n=21), refuse to URD search (n=14), unwillingness to undergo transplantation with available URD (n=5) and donor refuse to donate (n=2). Salvage allo-HSCT was allowed after relapse and actually 5 patients in the chemotherapy group received transplantation from URD donor (n=2) or haplo-identical donor (n=2) in the subsequent remission. The clinical characteristics such age, sex, initial WBC, and Philadelphia chromosome are all distributed equally in the two groups. With a median follow-up of 18 months for the whole group, 30 patients relapsed with estimated 3-year relapse rate (RR) at 58.1±8.5%. The 3-year event-free survival (LFS), non-relapse mortality (NRM) and overall survival (OS) were 38.0±7.9%, 11.1±4.4% and 46.0±9.0% respectively. In the URD allo-HSCT group, RR was 30.6±11.4% which was significantly lower than chemotherapy group (80.5±10.1%, p<0.001) while NRM was higher (16.4±6.7% vs. 0, p=0.028). Overall, 3-year LFS was superior in URD allo-HSCT group compared to chemotherapy (57.8±10.6% vs. 19.5±10.5%; median not reached vs. 13 months, p=0.002) and 3-year OS was also improved in URD allo-HSCT group (63.5±13.3%, median not reached versus 31.6±10.6%, median 24 months, p=0.016). Based on our data, URD allo-HSCT significantly reduced the relapse rate in high-risk ALL and the benefit translated into improvement in both LFS and OS. Prospective randomized study based on availability of HLA matched URD is warranted to confirm the exact role of URD transplantation in adult ALL. Table 1. Patient's characteristics Chemotherapy URD-allo-HSCT P value No of patients N=42 N=32 Median Follow-up (months) 15 (7.7∼48) 22 (8.2∼49) Sex (M/F) 19/23 21/11 0.08 Age 24.5 (16∼60) 25 (16∼57) 0.10     >35 14 9 0.61     <=35 28 23 Initial WBC (×109/L) 80.3 (15.3∼97.9) 61.5 (3.2∼98.4) 0.12 Cytogenetics     Ph+ 8 10 0.33     Ph− 33 22 Table 2. Clinical outcome in different treatment strategies Chemotherapy URD-allo-HSCT P value No of patients N=42 N=32 OS 31.6 ± 10.6% 63.5 ± 13.3% 0.016     median 24.9 months not reached LFS 19.5 ± 10.5% 57.8 ± 10.6% 0.002     median 13.2 months not reached Relapse rate 80.5 ± 10.1% 30.6 ± 11.4% <0.001 NRM 0% 16.4 ± 6.7% 0.028 Disclosures: No relevant conflicts of interest to declare.

scholarly journals AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR HIGH-RISK ACUTE LYMPHOBLASTIC LEUKEMIA: NON-RANDOMIZED STUDY WITH A MAXIMUM FOLLOW-UP OF MORE THAN 22 YEARS

2014 ◽  
Vol 6 (1) ◽  
pp. e2014047 ◽  
Author(s):  
Grzegorz Helbig ◽  
Malgorzata Krawczyk-Kulis ◽  
Malgorzata Kopera ◽  
Krystyna Jagoda ◽  
Patrycja Rzepka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem

Objective. To evaluate the efficacy and toxicity of autologous hematopoietic stem cell transplantation (AHSCT) for high-risk acute lymphoblastic leukemia (ALL). Material and methods. Overall, 128 high-risk ALL patients at a median age of 26 years (range 18-56 years) at diagnosis received AHSCT between 1991-2008. Induction treatment was anthracycline-based in all patients. Conditioning regimen consisted of CAV (cyclophosphamide, cytarabine, etoposide) in 125 patients whereas 3 subjects received cyclophosphamide and TBI (total body irridation). Bone marrow was stored for 72 hours in 4oC and re-infused 24 hours after conditioning completion. Bone marrow was a source of stem cells in 119 patients, peripheral blood in 2 and 7 subjects received both bone marrow and peripheral blood. Results. With a median follow-up after AHSCT of 1.6 years (range 0.1-22.3 years), the probability of leukemia-free survival (LFS) for the whole group at 10 years was 27% and 23% at 20 years. Transplant-related mortality at 100 days after AHSCT was 3.2%.. There was a strong tendency for better LFS for MRD-negative patients if compared with patients who had positive or unknown MRD status at AHSCT (32% vs 23% and 25%, respectively; p=0.06). There was no difference in LFS between B- and T-lineage ALL as well as between patients transplanted in first complete remission (CR1) and CR2. LFS at 10 years for patients with detectable BCR-ABL at transplant was 20% and this was comparable with subjects with negative and missing BCR-ABL status (26% and 28%; p=0.97). Conclusions. The results of AHSCT for high-risk ALL remains unsatisfactory with low probability of long-term LFS.

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