scholarly journals Haploidentical Allogeneic Stem Cell Transplantation in Poor Risk Cytogenetic Acute Myeloide Leukemia: Results in 33 Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5942-5942
Author(s):  
Elisa Sala ◽  
Rasha Salama Mohamed ◽  
Matteo Giovanni Carrabba ◽  
Carlo Messina ◽  
Maria Teresa Lupo Stanghellini ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Disease Relapse ◽  
Disease Free ◽  
Related Mortality

Abstract Introduction Complex Karyotype (CK), monosomy of chromosome 7 or 5 and Monosomal Karyotype (MK) are associated with a dismal outcome in Acute Myeloid Leukemia (AML) patients (pts). Allogeneic stem cell transplantation (allo-SCT) can be considered the only potentially curative option for these pts. Conventional allo-SCT strategies confer long term Overall Survival (OS) of around 20%. No data are available on the role of haploidentical stem cell transplantation (haplo-SCT) in this high risk setting. We reviewed our experience to address this issue. Patients and methods This retrospective analysis included adult AML pts treated at San Raffaele Hospital. Between November 2001 and April 2014, 33 consecutive pts with poor cytogenetic risk AML with monosomy of chromosome 7 or 5 (12/33 pts), MK (3/33 pts) and CK (18/33 pts) received haplo-SCT. Karyotypes were obtained from diagnostic bone marrow samples with standard methods and in accordance with International System of Human Cytogenetic Nomenclature guidelines. OS and Disease Free Survival (DFS) were calculated using the Kaplan-Meier product-limit method. Results Median age of pts at transplant was 50 years (range, 22 to 65). At the time of haplo-SCT, 10 pts (30%) were in complete remission (8 were in first complete remission), while 23 (70%) had active disease. Patients received a myeloablative conditioning regimen, Treosulfan-based. Twenty seven out of 33 pts received a T-cell repleted haplo-SCT, 6 pts a T-cell depleted haplo-SCT. In those pts who received a T-cell repleted transplant, GvHD prophylaxis was based on Cyclosporin and Methotrexate (7/27 cases) or Rapamycine and Mycophenolate Mofetil (20/27 cases). All 27 pts received Antithymocyte Globulin. Median follow-up after haplo-SCT was 304 days (range, 5 to 2897 days). Of 33 pts, 30 (91%) were in CR at day +30 after transplant, 1 died of sepsis before disease evaluation, 2 had disease persistence. At the last follow-up 11 out of 33 pts (34%) were alive, all of whom in CR, 22 pts (66%) died for the following causes: disease relapse/progression 10 (45%), Graft versus Host Disease 3 (14%), infection 9 (41%). Transplant related mortality (TRM) was 35.2% at 1 year and 35.2% at 3 years after transplant. Extimated DFS from day 30 after transplant was 34.5% at 1 year and 28% at 3 years. Extimated OS for all pts was 45% at 1 year and 22.6% at 3 years. Discussion Our data support haplo-SCT as a potentially curative option for AML pts with high risk cytogenetic abnormalities. Despite a TRM of 35% at 3 years, 1/3 of these pts achieved a long term disease free status. In the setting of a disease with extremely poor therapeutic options, haplo-SCT appears promising and not inferior to other sources of allogeneic stem cell transplantation. Transplantation strategies aimed at reducing transplant related mortality or disease relapse should be explored in order to improve these results and achieve a better outcome. Disclosures No relevant conflicts of interest to declare.

scholarly journals Long-term follow-up of persisting mixed chimerism after partially T cell-depleted allogeneic stem cell transplantation

Leukemia ◽  
2002 ◽  
Vol 16 (1) ◽  
pp. 13-21 ◽  
Author(s):  
N Schaap ◽  
A Schattenberg ◽  
E Mensink ◽  
F Preijers ◽  
M Hillegers ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Mixed Chimerism ◽  
Long Term Follow Up

scholarly journals The Burden of Survivorship on Hematological Patients—Long-Term Analysis of Toxicities after Total Body Irradiation and Allogeneic Stem Cell Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5640
Author(s):  
Michael Oertel ◽  
Jonas Martel ◽  
Jan-Henrik Mikesch ◽  
Sergiu Scobioala ◽  
Christian Reicherts ◽  
...  
Keyword(s):  
Stem Cell ◽  
Side Effects ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Total Body Irradiation ◽  
Whole Body ◽  
Total Body

Total body irradiation is an effective conditioning modality before autologous or allogeneic stem cell transplantation. With the whole body being the radiation target volume, a diverse spectrum of toxicities has been reported. This fact prompted us to investigate the long-term sequelae of this treatment concept in a large patient cohort. Overall, 322 patients with acute leukemia or myelodysplastic syndrome with a minimum follow-up of one year were included (the median follow-up in this study was 68 months). Pulmonary, cardiac, ocular, neurological and renal toxicities were observed in 23.9%, 14.0%, 23.6%, 23.9% and 20.2% of all patients, respectively. The majority of these side effects were grades 1 and 2 (64.9–89.2% of all toxicities in the respective categories). The use of 12 Gray total body irradiation resulted in a significant increase in ocular toxicities (p = 0.013) and severe mucositis (p < 0.001). Renal toxicities were influenced by the age at transplantation (relative risk: 1.06, p < 0.001) and disease entity. In summary, total body irradiation triggers a multifaceted, but manageable, toxicity profile. Except for ocular toxicities and mucositis, a 12 Gray regimen did not lead to an increase in long-term side effects.

Allogeneic Stem Cell Transplantation with Reduced-Intensity, Fludarabine-Based Conditioning in Relapsed and Refractory Hodgkin’s Disease: Low Transplant-Related Mortality and Impact of Intensity of Conditioning Regimen on Survival.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2135-2135
Author(s):  
Paolo Anderlini ◽  
Rima Saliba ◽  
Michele Donato ◽  
Sergio Giralt ◽  
Borje Andersson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Hodgkin’S Disease ◽  
Conditioning Regimen ◽  
Related Mortality

Abstract Forty patients with relapsed or refractory Hodgkin’s disease (HD) underwent allogeneic stem cell transplantation (allo-SCT) following a fludarabine-based conditioning regimen from an HLA-identical sibling (n=20) or a matched unrelated donor (n=20). The median age was 31 years (range 18-58). The median number of chemotherapy regimens received prior to allo-SCT was five (range 2-9). Thirty (75%) and thirty (75%) patients had received prior radiotherapy or a prior autologous SCT, respectively. The median time to progression after autologous SCT was nine months (3–52). Disease status at SCT was refractory relapse (n=14) or sensitive relapse (n=26). The conditioning regimens employed were fludarabine (25 mg/m sq IV x 5 days)-cyclophosphamide (1 g/m sq IV x 3 days) ± antithymocyte globulin (30 mg/kg IV x 3 days) (FC±ATG) (n=14), a less intensive regimen, and fludarabine (25 mg/m sq IV x 5 days) -melphalan (70 mg/m sq IV x 2 days) (FM) (n=26), a more intensive one. The two groups had similar demographics and prognostic factors. Chimerism studies indicated 100% donor-derived engraftment in 26/26 (100%) FM patients and in 9/13 (69%) evaluable FC±ATG patients. Day 100 and cumulative (18-month) transplant-related mortality (TRM) were 5 % and 22%, respectively for the whole group. There was a nonsignificant trend towards a lower cumulative TRM in the FM group (18% vs. 30% at 18 months, p=0.2). The cumulative incidence of acute (grade II-IV) GVHD was 38%. The cumulative incidence of chronic GVHD at 18 months was 69%. There was a trend for a lower relapse rate after the occurrence of GVHD, however, this was not statistically significant (hazard ratio 0.8; p= 0.6). Progression rates were similar in the FM and FC patients (53% vs. 57% respectively at 18 months, p=0.4). However, disease progression occurred later in FM patients (range 2–34 months) than in FC patients (range 0.7–13 months). In addition, with comparable follow-up time after progression, the FM group experienced a lower death rate after progression. Twenty-four patients (60%) are alive (fourteen in complete remission) with a median follow-up of 13 months (4–78). Sixteen patients expired (TRM n=8, disease progression n=8). FM patients had significantly better overall survival (73% vs. 39% at 18 months; p=0.03), and a trend towards better progression-free survival (37% vs. 21% at 18 months; p=0.2). We conclude that allo-SCT with fludarabine-based, less intensive conditioning from matched related and unrelated donors are feasible in high-risk HD patients with a low TRM. The intensity of the preparative regimen affects survival.

Allogeneic Stem Cell Transplantation in Angioimmunoblastic T-Cell Lymphoma (AITL): A Retrospective Survey from the Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3042-3042
Author(s):  
Charalampia Kyriakou ◽  
C. Canals ◽  
G. Taghipour ◽  
J. Finke ◽  
H. Kolb ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Allogeneic Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
T Cell Lymphoma

Abstract AITL is a rare peripheral T-cell lymphoma characterised by an aggressive behaviour, which primarily affects the elderly. Chemotherapy regimens fail to alter the high relapse rate and overall survival hardly exceeds 25% at 5 years. To date, there is no information on the potential role of allogeneic stem cell transplantation (allo-SCT) in the management of AITL. We report the outcome of 39 patients with a median age of 47 years (24–68), who underwent an allo-SCT between 1995 and 2004 for AITL, and were reported to the EBMT registry. The median time from diagnosis to transplant was 10 months (4–72). Thirty-four patients (87%) had previously received two or more treatment lines, and 16 patients (41%) a previous autologous SCT. Fifteen patients (38%) had a primary refractory disease, 13 (33%) were transplanted in partial remission and the remaining patients were in complete remission (CR) (mostly in 2nd and 3rd CR). Twenty-four patients were transplanted from an HLA-identical sibling and 15 from a matched unrelated donor. A myeloablative conditioning regimen (MAC) was used in 21 patients (cyclophosphamide + total body irradiation in 14), while 18 patients received fludarabine-based reduced intensity conditionings (RIC). Peripheral blood was the source of stem cells in 35 patients (90%). Three patients failed to engraft (one patient in the RIC group). Twenty-one patients (54%) developed acute graft versus host disease (grade I-II, n=16; grade III-IV, n=5). Twenty-eight patients (72%) achieved a CR after the allogeneic procedure. Nine patients died from transplant related mortality (TRM) and 5 patients from disease progression. The cumulative incidence of TRM at 12 months was 19% for the MAC and 26% for the RIC group. After a median follow-up for the surviving patients of 20 months (6–74), 25 patients are alive. Relapse rates at 1 and 3 years were estimated at 10% and 18% for the MAC and 16 and 20% for the RIC patients. Progression free survival rates at 3 years were 67% and 50% and the overall survival at the same time 71% and 56% for the MAC and RIC group of patients, respectively. Although follow up is rather short, these data suggest that allo-SCT results in good overall response and is associated with a low relapse rate in this group of poor risk heavily pre-treated and rather elderly group of AITL patients. Allo-SCT could be considered a therapeutic option for eligible high-risk AITL patients. Nevertheless, the impact of this approach should be further explored in prospective collaborative studies.

Long Term Follow-up of the Prospective Multicenter Study of reduced-Intensity Allogeneic Stem Cell Transplantation for Primary or Post ET/PV Myelofibrosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1019-1019 ◽  
Author(s):  
Haefaa Alchalby ◽  
Tatjana Zabelina ◽  
Daniel Wolff ◽  
Guido Kobbe ◽  
Martin Bornhäuser ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Allogeneic Transplantation ◽  
Prospective Multicenter Study ◽  
Long Term Follow Up ◽  
Reduced Intensity

Abstract Abstract 1019 Allogeneic stem cell transplantation is the only curative treatment for myelofibrosis. Here we present a long–term follow up of patients with myelofibrosis treated with reduced-intensity allogeneic stem cell transplantation in the prospective multicenter study conducted by the MDS subcommittee of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) (study registration NCT 00599547). From 2002 to 2007, a total of 103 patients with primary (63 pts) or post-polycythemia vera and –essential thrombocythemia myelofibrosis (40 pts) from seventeen transplantation centers in three nations were included in the study. There were 62 males and 41 females with a median age of 55 years (range, 32–68 years). Risk profile according to Lille score was low risk with constitutional symptoms (17%), intermediate risk (53%) and high risk (30%). All but three of the patients received peripheral stem cells as stem cell source from either related (n=33) or unrelated donor (n=70) and a conditioning with Busulfan (10mg/kg orally or 8mg/kg intravenously),Fludarabin (180 mg/m2) and antithymocyte-globulin (ATG-Fresenius®) according a previously published protocol. According to high-resolution HLA typing, 21 patients had at least one allele or antigen HLA mismatch. From 88 patients with a known JAK2V617F-status 63 harbored the mutation. After a median follow up of 60 months (range 9–109 months), 41 patients had chronic graft vs. host disease which was extensive in the half of cases. The 5-year and 8-year estimated overall survival (OS) was 68% and 65%, respectively with a stable plateau after 5,3 years follow up (Figure-1). Estimated 5-year disease-free survival was 40%. The cumulative incidence of relapse/progression at 3 and 5 years was 22% and 28% and the non-relapse mortality at 1 and at 3 years was 18% ands 21%, respectively.Figure-1Figure-1. Within the overall follow up period, relapse/progression occurred in 28 patients. Twenty one of them were treated with donor-lymphocyte infusions (DLI) and/or a second allogeneic transplantation (n=11). Sixteen of those were at the last follow up alive. The estimated OS of all relapsed patients after a median follow up of 46 months (range 4–62 months) beginning from the time of relapse was 55%. In multivariate analysis advanced age >55years (HR: 4.69, p=0.001), absence of JAK2V617F mutation (HR: 2.50, p=0.02), mismatched donor (HR: 3.62, p=0.002) were significant independent predictors for reduced OS. This update of a prospective trial using reduced intensity conditioning followed by allogeneic stem cell transplantation for myelofibrosis confirmed a very good long-term OS. Relapse still occurs in about 30% and remains the main problem after transplantation. However, with adoptive immunotherapy using DLI or even second allogeneic transplantation a second remission with long term survival can be induced in about 50% of the relapsed patients. Developing methods for remission monitoring and early prediction and treatment of relapse should be the focus of future studies. Disclosures: Kobbe: Celgene: Consultancy, Research Funding; Ortho Biotec: Consultancy. de Witte:Novartis: Consultancy, Honoraria, Speakers Bureau.

Updated Long-Term Results of a Randomized Comparison of Prophylactic and Pre-Emptive Imatinib Following Allogeneic Stem Cell Transplantation for Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 247-247 ◽  
Author(s):  
Heike Pfeifer ◽  
B. Wassmann ◽  
Wolfgang A. Bethge ◽  
Jolanta Dengler ◽  
Martin Bornhäuser ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Molecular Techniques ◽  
Long Term Results ◽  
Rt Pcr ◽  
Post Transplant

Abstract Abstract 247 Background: The presence of minimal residual disease (MRD) after allogeneic stem cell transplantation (SCT) for Ph+ ALL is highly predictive of eventual relapse. Imatinib (IM) has very limited efficacy in hematologic relapse of Ph+ALL, but may prevent leukemia recurrence if started when the leukemia burden is still very low and detectable only by molecular techniques. The optimal time for starting IM post transplant and the prognostic relevance of different bcr-abl transcript levels in relation to time after SCT have not been established. Aims: To determine the impact of post-transplant IM, given either prophylactically or after detection of bcr-abl transcripts (pre-emptively), on the overall incidence of MRD, remission duration, long-term treatment outcome and tolerability in pts. who underwent SCT for Ph+ALL in complete remission. Study Design: In a prospective, randomized multicenter trial, previously transplanted Ph+ ALL pts. (n=55) were assigned to receive imatinib prophylactically (n=26) or pre-emptively (n=29). SCT was performed in CR1 in 23 pts. and 27 pts. in the two groups, respectively. Five pts.were transplanted in CR2. Serial assessment of bcr-abl transcripts was performed by quantitative RT-PCR and additionally by nested-RT-PCR if the sensitivity of the qRT-PCR was below the quantitative range. Confirmatory testing of a second independent sample was not required, to reduce the risk of treatment delays. Samples were considered PCR negative only if the ABL copy number exceeded 104. Imatinib administration was scheduled for one year of continuous PCR negativity. Results: IM was started in 24/26 pts. allocated to prophylactic IM and in 14/29 pts. in the pre-emptive arm. The majority of pts. received IM 400 mg/d (26/38 pts.), the other 12 pts. 600 mg IM daily. IM was started a median of 48 d after SCT in the prophylactic arm and 70 d after SCT with pre-emptive therapy. After a median follow-up of 30 mos. and 32 mos., respectively, 82% and 78% of pts. are alive in ongoing CR, 4 pts. died in CR. Five pts. transplanted in CR1 and 2/5 pts. transplanted in CR2 have relapsed (median follow-up 9 mos. and 10.5 mos., respectively). The frequency of MRD positivity was significantly lower in pts. assigned to prophylactic imatinib (10/26; 40%) than those in the pre-emptive treatment arm (20/29; 69%) (p=0.046 by chi2 test). Only 9 of 29 pts. assigned to pre-emptive imatinib remained continuously PCR negative after SCT, with a median follow-up of 32 months (18–46 months) after SCT. The median duration of sustained, uninterrupted PCR negativity after SCT is 26.5 months with prophylactic and 6.8 months with pre-emptive administration of imatinib (p=0.065). The probability of remaing in CHR after SCT was significantly lower in partients who remained MRD negative after SCT (p=0.0002). Analysis of the kinetics of molecular relapse showed that detection of bcr-abl transcripts within 100 days of transplant, despite rapid initiation of IM, was associated with a significantly inferior EFS compared to first detection of MRD positivity more than 100 days after SCT. IM was discontinued prematurely in 54% pts. receiving imatinib prophylactically and in 64% of pts. receiving imatinib pre-emptively, mostly due to gastrointestinal toxicity. Accordingly, the time to IM discontinuation was 245 d and 191 d in the prophylactic and the pre-emptive treatment arms, respectively. Despite this early discontinuation rate, overall survival in the two treatment groups was 80% and 74.5% after 5 years, with no significant difference by log rank test (p=0.84). Conclusions: Prophylactic administration of imatinib significantly reduces the incidence of molecular relapse after SCT. Both interventional strategies are associated with a low rate of hematologic relapse, durable remissions and excellent long-term outcome in patients with Ph+ ALL. The presence of MRD both prior to and early after SCT identifies a small subset of patients with a poor prognosis despite post-transplant imatinib, and warrants testing of alternative approaches to prevent hematologic relapse. Disclosures: Schuld: Novartis: Employment. Goekbuget:Micromet: Consultancy. Ottmann:Novartis Corporation: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding.

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