Current trends in hematopoietic stem cell transplantation in Europe

Blood ◽  
2002 ◽  
Vol 100 (7) ◽  
pp. 2374-2386 ◽  
Author(s):  
Alois Gratwohl ◽  
Helen Baldomero ◽  
Bruno Horisberger ◽  
Caroline Schmid ◽  
Jakob Passweg ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Chronic Myeloid Leukemia ◽  
Solid Tumors ◽  
Myeloid Leukemia ◽  
European Countries ◽  
Medium Term ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Autologous Hsct ◽  
Acute Myeloid

Major changes have occurred in the transplantation of hematopoietic stem cells (HSCs) during the last decade. This report reveals the changes, reflects current status, and provides medium-term projections of HSC transplantation (HSCT) development in Europe. Data on 132 963 patients, 44 165 with allogeneic HSC transplant (33%) and 88 798 with an autologous HSC transplant (67%), collected prospectively from 619 centers by the European Group for Blood and Marrow Transplantation (EBMT) in 35 European countries between 1990 (4234 HSCTs) and 2000 (19 136 HSCTs) illustrate utilization of HSCT. HSCT increased in all European countries and for all indications. There were major differences depending on disease indication and donor type. Transplantation rates (numbers of HSCTs per 10 million inhabitants) varied from less than 1 for some rare indications to 37.7 ± 4.1 for acute myeloid leukemia in allogeneic HSCT or 95.5 ± 13.5 for non-Hodgkin lymphoma in autologous HSCT. There were indications with a steady, continuing increase and others with initial increase but subsequent decrease. Projections on medium-term development for each disease based on a weighted sensitivity analysis predict an ongoing increase in allogeneic HSCT except for chronic myeloid leukemia. In autologous HSCT they predict an increase for lymphoproliferative disorders, acute myeloid leukemia, myelodysplastic syndromes, and some solid tumors but a decrease for most solid tumors, acute lymphoid leukemia, and chronic myeloid leukemia. Transplantation rates can be predicted with reasonable sensitivity for most disease indications. Despite marked changes in the rapidly developing field of HSCT, this information on current use, trends, and midterm predictions forms a rational basis for patient counseling and health care planning.

Prospective Evaluation of Allogeneic Hematopoietic Stem-Cell Transplantation From Matched Related and Matched Unrelated Donors in Younger Adults With High-Risk Acute Myeloid Leukemia: German-Austrian Trial AMLHD98A

2010 ◽  
Vol 28 (30) ◽  
pp. 4642-4648 ◽  
Author(s):  
Richard F. Schlenk ◽  
Konstanze Döhner ◽  
Silja Mack ◽  
Michael Stoppel ◽  
Franz Király ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Younger Adults ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Acute Myeloid

Purpose To assess the impact of allogeneic hematopoietic stem-cell transplantation (HSCT) from matched related donors (MRDs) and matched unrelated donors (MUDs) on outcome in high-risk patients with acute myeloid leukemia (AML) within a prospective multicenter treatment trial. Patients and Methods Between 1998 and 2004, 844 patients (median age, 48 years; range, 16 to 62 years) with AML were enrolled onto protocol AMLHD98A that included a risk-adapted treatment strategy. High risk was defined by the presence of unfavorable cytogenetics and/or by no response to induction therapy. Results Two hundred sixty-seven (32%) of 844 patients were assigned to the high-risk group. Of these 267 patients, 51 patients (19%) achieved complete remission but had adverse cytogenetics, and 216 patients (81%) had no response to induction therapy. Allogeneic HSCT was actually performed in 162 (61%) of 267 high-risk patients, after a median time of 147 days after diagnosis. Graft sources were as follows: MRD (n = 62), MUD (n = 89), haploidentical donor (n = 10), and cord blood (n = 1). The 5-year overall survival rates were 6.5% (95% CI, 3.1% to 13.6%) for patients (n = 105) not proceeding to HSCT and 25.1% (95% CI, 19.1% to 33.0%; from date of transplantation) for patients (n = 162) receiving HSCT. Multivariable analysis including allogeneic HSCT as a time-dependent covariable revealed that allogeneic HSCT significantly improved outcome; there was no difference in outcome between allogeneic HSCT from MRD and MUD. Conclusion Allogeneic HSCT in younger adults with high-risk AML has a significant beneficial impact on outcome, and allogeneic HSCT from MRD and MUD yields similar results.

Intravenous Busulfan-Based Myeloablative Conditioning Is Comparable to TBI-Based Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Recipients with Acute Myeloid Leukemia: A Nationwide Retrospective Study From the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1922-1922
Author(s):  
Takuya Yamashita ◽  
Takahiro Fukuda ◽  
Shuichi Taniguchi ◽  
Kazuteru Ohashi ◽  
Saiko Kurosawa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Conditioning Regimens ◽  
Acute Myeloid

Abstract Abstract 1922 In allogeneic hematopoietic stem cell transplantation (HSCT) for recipients with acute myeloid leukemia (AML), cyclophosphamide (Cy) combined with total body irradiation (TBI) (Cy+TBI) is the most common myeloablative conditioning (MAC) regimen, but busulfan (Bu) in combination with Cy (Bu+Cy) has been an alternative to Cy+TBI since early 1980s. But as oral Bu has a problem of interpatient variation in intestinal absorption, intravenous Bu (ivBu) has been developed and substituted for Bu in conditioning regimens for HSCT. For the last decade, fludarabine (Flu)-based regimens with the addition of cytotoxic agents such as Bu or melphalan (L-PAM) have been developed as reduced-intensity conditioning (RIC) regimens. After the introduction of ivBu, Flu+ivBu has become one of the common RIC regimens. In Japan, ivBu was introduced in 2006 and have been widely used as a part of conditioning regimens. In this nationwide retrospective study, we evaluated the clinical outcomes of allogeneic HSCT for AML, especially focusing on ivBu-based conditioning regimens. The study population included HSCT recipients reported to the Japan Society for Hematopoietic Cell Transplantation. From this database, we extracted the data of adult patients with AML who received first allogeneic HSCT between 1975 and 2010. There were 9,396 recipients selected according to this criterion. Then, we excluded 345 (3.7%) cases from the study because of missing key variables. A total of 9,051 recipients were evaluated in this study. Median age at transplant was 43 years (range, 16–82), and 41.8% (n=3,785) were female. Types of transplant included bone marrow transplantation from sibling donor (RBMT) (n=1,978, 21.9%), peripheral blood stem cell transplantation from sibling donor (RPBSCT) (n=1,411, 15.6%), bone marrow transplantation from unrelated donor (UBMT) (n=3,321, 36.7%) and cord blood transplantation from unrelated donor (CBT) (n=1,728, 19.1%). MAC regimens were applied to 80.2% (n=7,259) of recipients and RIC regimens to 19.8% (n=1,792), according to the definitions proposed by the NMDP and the CIBMTR in 2007. These MAC regimens included Bu+Cy-based (12.4% of all MAC regimens), Cy+TBI-based (50.0%) and ivBu+Cy-based (5.6%) regimens. RIC regimens consisted mainly of Flu+Bu-based (27.6% of all RIC regimens), Flu+L-PAM-based (24.1%) and Flu+ivBu-based (19.5%) regimens. Median follow-up of survivors was 1,437 days (range, 26–8,344). In MAC setting, overall survival (OS) of HSCT recipients with ivBu+Cy-based regimens did not show the significant difference between that with Bu+Cy or Cy+TBI-based ones in RBMT (p=0.168), RPBSCT (p=0.236) and UBMT (p=0.604). But in CBT, Cy+TBI was significantly superior to Bu+Cy (p=0.004). Though the cumulative incidences of relapse (RI) were similar among recipients with these three regimens, the cumulative incidence of non-relapse mortality (NRM) with Bu+Cy was significantly higher than with Cy+TBI in CBT (p=0.049). In RIC setting, OS of recipients with Flu+ivBu-based regimens was comparable to that with Flu+Bu or Flu+L-PAM-based ones regardless of the type of transplant. RIs with these three regimens were almost equivalent, but NRM with Flu+ivBu-based was significantly lower than that with Flu+L-PAM-based in UBMT (p=0.023). In the multivariate analysis for OS, ivBu+Cy-based regimens did not have significant impacts regardless of the type of transplant, but Flu+ivBu-based regimen had a significantly favorable impact in RBMT (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.23–0.99). In the multivariate analysis for NRM, Flu+ivBu-based regimen had a significantly reduced risk compared with Flu+L-PAM in RBMT (HR 0.32, 95%CI 0.11–0.95) and UBMT (HR 0.46, 95%CI 0.25–0.83). These data indicates that ivBu+Cy-based and Cy+TBI-based MAC regimens have almost equivalent efficacy profiles for OS, RI and NRM, and Flu+ivBu-based RIC regimens can reduce the risk of NRM compared with Flu+Bu and Flu+L-PAM-based ones in allogeneic HSCT for recipients with AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prolonged Survival of a Refractory Acute Myeloid Leukemia Patient after a Third Hematopoietic Stem Cell Transplantation with Umbilical Cord Blood following a Second Relapse

2014 ◽  
Vol 2014 ◽  
pp. 1-3
Author(s):  
Suk-young Lee ◽  
Naoki Kurita ◽  
Koichiro Maie ◽  
Masanori Seki ◽  
Yasuhisa Yokoyama ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Acute Myeloid

Although hematopoietic stem cell transplantation (HSCT) has been considered to be the only way for potential cure of relapsed acute myeloid leukemia (AML), there has been no report on a third HSCT in patients with multiple relapsed AML. Here, we report a case of 53-year-old female who received a successful third allogeneic HSCT after relapse of AML following a second allogeneic HSCT. She was treated with a toxicity reduced conditioning regimen and received direct intrabone cord blood transplantation (CBT) using a single unit of 5/6 HLA-matched cord blood as a graft source. Graft-versus-host disease prophylaxis was performed with a single agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission for 8 months since the direct intrabone CBT. This report highlights not only the importance of individually adjusted approach but also the need for further investigation on the role of HSCT as a treatment modality in patients with refractory or multiple relapsed AML.

Allogeneic hematopoietic stem cell transplantation to improve survival in acute myeloid leukemia patients with FLT3 internal tandem duplication.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17014-e17014
Author(s):  
Po-Han Lin ◽  
Hwai-I Yang ◽  
Li-Yuan Bai ◽  
Su-Peng Yeh ◽  
Chang-Fang Chiu
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Internal Tandem Duplication ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Fab Classification ◽  
Acute Myeloid

e17014 Background: Fms-like tyrosine kinase (FLT3) gene with internal tandem duplication (ITD) is a poor prognostic factor in patients with acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (HSCT) is considered as an effective treatment for AML patients with poor risk. However, the efficacy of allogenic HSCT in the treatment of AML patients with FLT3-ITD was not clear. Methods: A total of 122 patients, who were newly diagnosed as de novo AML and received intensive chemotherapy at China Medical University Hospital between 2003 January and 2010 December, were retrospectively analyzed. At diagnosis, all patients received French-American-British (FAB) classification, cytogenetic analyses and immunophenotyping. The HSCT was performed on the basis of the consensus of the hematologists in this institute, mainly according to the two factors: unfavorable karyotype and suitable donor availability. The FLT3-ITD was detected by polymerase chain reaction and confirmed by direct sequencing. The Cox proportional hazards regression analysis was used to estimate the hazards ratios of the overall survival and corresponding 95% confidence interval (CI) for various combinations of FLT3-ITD and HSCT status. Results: An FLT3-ITD was detected in 34 patients (27.9%). The allogeneic HSCT was performed in 39 patients; 29 patients with wild type (wt)-FLT3 and 10 patients with FLT3-ITD. The number of death/number of patients (medium overall survival) of wt-FLT3/HSCT(+), wt-FLT3/HSCT(-), FLT3-ITD/HSCT(+) and FLT3-ITD/HSCT(-) was 12/29 (53.4 months), 25/59 (40.7 months), 3/10 (medium not reached) and 17/24 (12.0 months), respectively (p=0.014). Comparing with wt-FLT3/HSCT(-) patients, the hazard ratio (95% CI) of overall survival for wt-FLT3/HSCT(+), FLT3-ITD/HSCT(+) and FLT3-ITD/HSCT(-) was 1.39 (0.61-3.18), 0.40 (0.11-1.49), and 3.57 (1.58-8.09), respectively, after adjustment of age, sex, WBC, LDH, karyotype and FAB classification. Conclusions: AML patients without FLT3-ITD had better survival than those with FLT3-ITD regardless of the allogeneic-HSCT. The allogeneic HSCT may improve overall survival in AML patients with FLT3-ITD.

Prospective Evaluation of Azacitidine Maintenance Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5476-5476 ◽  
Author(s):  
Harinder Gill ◽  
Albert Kwok Wai Lie ◽  
Yok Lam Kwong ◽  
Anskar Y.H. Leung
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Poor Risk ◽  
Acute Myeloid

Abstract Introduction and aim. Relapse following allogeneic hematopoietic stem cell transplantation (HSCT) is a major cause of treatment failure and is associated with a poor prognosis. Overall survivals are around 50% at 5 years following allogeneic HSCT in intermediate and high risk AML. Survivals remain less than 20% in poor-risk and very poor-risk patients based on the cytogenetic profile. Thus, prevention of relapse following allogeneic HSCT remains an unmet clinical need. Low-dose azacitidine maintenance post-HSCT has been shown to augment graft-versus-leukemia effect and may prolong survivals. We aim to prospectively evaluate the effect of azacitidine maintenance following allogeneic HSCT in high risk AML and MDS. Method. Consecutive patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in remission following first allogeneic HSCT or second allogeneic HSCT (from the original donor) were recruited. High risk AML in this study comprised patients with poor risk karyotype, secondary AML transformed from underlying MDS, presence of fms-like tyrosine kinase 3-internal tandem duplication (FLT3 -ITD) and non-remission before HSCT. Azacitidine was administered at 100mg daily for 3 days per cycle every 28 days until progression or a maximum of 8 cycles. The clinicopathologic and treatment characteristics were determined. The occurrence of graft-versus-host disease (GVHD) was determined. DNA chimerism was determined in the bone marrow before the initiation of azacitidine, after 4th and 8th cycles of azacitidine and at 1 year. DNA chimerism was determined by quantification of polymorphic short tandem repeat sequences. The progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier analysis. Results. Thirty-four patients with high-risk AML (N=31) and MDS (N=3) were recruited. The median duration of follow-up was 14 months (range: 2 - 44 months). Twenty-two patients received azacitidine maintenance after first allogeneic HSCT, whereas 12 patients received azacitidine maintenance after a second allogeneic HSCT from the same donor following relapse from a first allogeneic HSCT For patients receiving azacitidine after first HSCT, at a median follow-up of 18.5 months (range: 5- 36 months), the median PFS was not reached, and the median OS was 32 months (95% confidence interval [C.I.]: 24.85-39.15). The 24-month PFS and OS were 66.1% and 73.2% respectively. Acute and chronic GVHD occurred in 7 (31.8%) and 17 patients (77%). For patients receiving azacitidine after second HSCT, at a median follow-up of 14 months (range: 9 - 46 months), the median PFS and OS were 9 months (95% C.I.:6.94-11.04) and 14 months (range: 11.77 - 16.23 months). The 24-month PFS and OS were 25% and 14% respectively. Acute and chronic GVHD occurred in 1 (8.3%) and 5 (41.7%) patients respectively. In both groups, 100% donor chimerism was achieved during azacitidine maintenance. Conclusion. Azacitidine maintenance following first allogeneic HSCT resulted in favorable 2-year survivals in selected patients with high-risk AML and MDS. Nevertheless, survivals were poor despite azacitidine maintenance after second allogeneic HSCT from the same donor. Full donor chimerism was maintained during azacitidine maintenance. Disclosures No relevant conflicts of interest to declare.

scholarly journals Adverse Prognosis in Acute Myeloid Leukemia with Abnormality Abn(3q): Does EVI1 Matter?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1309-1309
Author(s):  
Theresa Kretschmann ◽  
Christoph Röllig ◽  
Brigitte Mohr ◽  
Michael Kramer ◽  
Matthias Stelljes ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Chromosome 3 ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Cytogenetic Aberrations ◽  
The Impact ◽  
Acute Myeloid

Abstract Introduction: The ELN classification of cytogenetic aberrations in acute myeloid leukemia (AML) distinguishes favorable risk, intermediate risk I and II and adverserisk. The adverse-risk group contains patients (pts) with inv(3) and t(3;3). These pts have a significantly poorer outcome compared to other cytogenetic aberrations. The MRC classification considers both pts with inv(3) and t(3;3) as well as patients with other abn(3q) as adverse risk, but excludes t(3;5). Pts with inv(3) or t(3;3) have breakpoints located on the long arm of chromosome 3 at q21 and q26. As a result of these chromosomal modifications, an enhancer-protein is deregulated and the stem-cell regulator zinc finger protein EVI1 on 3q26 is over expressed. Other 3q aberrations do not involve EVI1. We conducted a comparative analysis on the impact of abn(3q) with likely EVI1 alteration versus abn(3q) without EVI1 involvement. Analyses were done both in the entire group of abn(3q) pts and in the subgroup of pts treated with allogeneic hematopoietic stem-cell transplantation (HSCT). Methods: We performed a retrospective analysis on 163 patients with an abnormality on the q arm of chromosome 3 (abn(3q)). These pts were treated between 1996 and 2009 in three multicenter studies by the German SAL study group (AML2003, AML96, AML60+). Pts with t(3;5) were excluded (n=11). The remaining 152 patients were divided into two groups. Group 1 (EVI1) contained 56 patients with a chromosomal aberration likely to alter EVI1, i.e. t(3;3), inv(3) and abn(3)(q26). Group 2 (noEVI1) comprised the remaining 96 patients displaying other abn(3q) aberrations. We compared groups for baseline characteristics, complete remission (CR), relapse-free survival (RFS) and overall survival (OS) in total and stratified for treatment. Results: Descriptive comparison of the groups (EVI1 vs noEVI1) revealed a significantly higher WBC count (14.3 vs 4.6 Gpt/l), PLT count (62 vs 47 Gpt/l) and -7 incidence (29% vs 16%) in the EVI1 group, whereas in the noEVI1 group, complex aberrations (25% vs 74%) and 17p alterations (0% vs 24%) occurred in a higher proportion of pts. CR rates (52% vs 47%), median RFS (7 vs 6 months) and median OS (6 vs 7 months) did not differ significantly between the two groups. In order to explore the clinical behavior of the different abn(3q) aberrations in relation to allogeneic HSCT, we compared EVI1 pts (n=21) versus noEVI1 pts (n=38) who received an allogeneic HSCT at any time during treatment. Patients with aberrant EVI1 were significantly younger (median age 44 vs 52 years), had a higher incidence of -7 (29% vs 13%), but less frequent karyotype complexity (10% vs 74%) or 17p alterations (0% vs 24%). More patients in the EVI1 group achieved a first CR before HSCT (95% vs 84%). Amongst CR pts, median RFS was slightly higher in the EVI1group (9 vs 6 months). In all abn(3q) pts with allogeneic HSCT, median OS was 30 months in the EVI1 group and only 12.5 months in the noEVI1 group. According to the log-rank test, this difference did not reach statistical significance (p=0.137). The advantage in mean OS for EVI1 patients is most likely due to the higher proportion of patients transplanted in CR while the accumulation of complex karyotypes in the noEVI1 group caused more primary resistant AML cases with a rapid progression even after allogeneic HSCT. Conclusions: Although AML development may be based on different molecularbiological mechanisms in patients with different abn(3q) aberrations depending on EVI1 alteration, the prognosis of the two groups is very similar. The most likely reason is the equal balance of favorable and adverse prognostic factors between the two groups such as age, karyotype complexity, 17p alteration and -7. Patients of both groups benefit from allogeneic HSCT to a similar extent. Confirmation of these results on larger data sets is desirable and under way. Disclosures Baldus: Novartis: Research Funding. Einsele:Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen/Onyx: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Thiede:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AgenDix GmBH: Equity Ownership.

scholarly journals Syngeneic hematopoietic stem cell transplantation for acute myeloid leukemia: a propensity score-matched analysis

2021 ◽  
Vol 11 (9) ◽  
Author(s):  
Shuhei Kurosawa ◽  
Shohei Mizuno ◽  
Yasuyuki Arai ◽  
Masayoshi Masuko ◽  
Junya Kanda ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Propensity Score ◽  
Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Acute Myeloid

AbstractThe present study evaluated outcomes and prognostic factors in adult patients with acute myeloid leukemia (AML) after syngeneic hematopoietic stem cell transplantation (HSCT). Among patients in first complete remission (CR1), outcomes of syngeneic HSCT (Syn) were compared with those of autologous HSCT (Auto), allogeneic HSCT from human leukocyte antigen (HLA)-matched sibling donor (MSD), or allogeneic HSCT from HLA-matched unrelated donor (MUD). Among 11,866 patients receiving first HSCT, 26 in the Syn group were analyzed. The 5-year overall survival (OS) rate, the cumulative incidence of relapse, and the cumulative incidence of non-relapse mortality (NRM) were 47.8%, 59.6%, and 4.6%, respectively. The OS was significantly better in patients in CR1 (n = 13) than in patients in non-CR1 (P = 0.012). Furthermore, 39 patients in CR1 each were assigned to the Auto, MSD, and MUD groups using propensity score matching. The 5-year OS in the Syn (68.4%) was not significantly different from those in the Auto (55.9%, P = 0.265), MSD (62.4%, P = 0.419), or MUD (63.7%, P = 0.409) groups. A higher relapse in the Syn than in the MSD and MUD groups was offset by lower NRM. In summary, syngeneic HSCT might be an alternative option for AML patients in CR1.

Impact of Incomplete Blood Count Recovery Prior to Allogeneic Hematopoietic Stem Cell Transplantation on Engraftment and Early Infection in Patients with Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3408-3408 ◽  
Author(s):  
Takeru Asano ◽  
Shuntaro Ikegawa ◽  
Tomoko Inomata ◽  
Naoto Ikeda ◽  
Hiroyuki Sugiura ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Low Dose ◽  
Early Infection ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Acute Myeloid ◽  
Neutrophil Engraftment ◽  
Count Recovery

Abstract Introduction: Hematological complete remission (CR) is the evident prognostic factor of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with Acute Myeloid Leukemia (AML). CR with incomplete blood cell count recovery (CRi) after induction therapy was identified as independent prognostic factor for inferior long-term outcomes in patients with AML achieving remission (Chen et al, JCO 2015). There is a paucity of data regarding the impact of response (CR vs. CRi) prior to allogeneic HSCT. Here we examined whether CRi provide prognostic information on the transplant outcomes. Methods: We retrospectively analyzed 73 consecutive adults with AML who received first allogeneic HSCT between 2008 and 2015. All clinical data were collected from medical records. CRi were defined CR with absolute neutrophil count < 1,000/mm3 and/or platelet count < 100,000/mm3. CR and CRi were confirmed just prior to allogeneic HSCT in bone marrow and peripheral blood. Cytogenetic risk group was assigned based on CIBMTR criteria. Chemotherapy regimens prior to allogeneic HSCT defined as follows; standard-dose (cytarabine plus anthracycline), high-dose (cytarabine at individual dose ≥ 1g/m2 with or without other drugs), low-dose (azacitidine or low dose cytarabine). Categorical and continuous variables were analyzed using Fisher's exact test and Mann-Whitney U test, respectively. Overall survival (OS) and relapse free survival (RFS) were estimated by Kaplan-Meiyer method. Cumulative incidence of relapse (CIR), non-relapse mortality (NRM), engraftment rate and cumulative infectious events were calculated using Grayfs method. Multivariate analysis was performed using the Fine-gray proportional hazard regression model for NRM and cumulative infectious events. Results: A total of 48 (66%) were in CR and 25 (34%) in CRi. The characteristics of the study population, donors and transplants stratified by blood count recovery pre-HSCT are summarized in Table 1. There were several statistically differences between patients in CR and CRi. More patients in CR had longer time from final chemotherapy to HSCT, lower HCT-CI and a higher proportion of major ABO mismatch donor. Median follow-up from allogeneic HSCT was 18 months (range, 1 to 80 months) in the patients still alive. Patients in CR and CRi had a similar 2-year OS (63% vs. 60%, p = 0.29), 2-year RFS (58% vs. 54%, p = 0.42) and 2-year CIR (30% vs. 19%, p = 0.64). 2-year NRM was significantly higher for patients in CRi (17% vs. 34%, p = 0.046) (Figure 1). Ten patients in CRi (40%) died after allogeneic HSCT. One patient died from relapse of AML. Causes of NRM were infection (n=2), veno-occlusive disease (n=3), respiratory failure (n=3) and chronic graft-versus-host disease (n=1). The median time of neutrophil engraftment was 15 days for patients in CR (range, 10 to 25 days) and 18 days for patients in CRi (range, 11 to 49 days). Engraftment rate of neutrophil for patients in CR and CRi was 96% and 92%, respectively. 2 patients in CRi died before neutrophil engraftment. Engraftment rate of neutrophil within 30 days after allogeneic HSCT was significantly lower for patients in CRi (96% vs 84%, p = 0.037). The median time of platelet engraftment was 22 days for patients in CR (range, 10 to 77 days) and 26 days for patients in CRi (range, 12 to 164 days). Engraftment rate of platelet for patients in CR and CRi was 92% and 80%, respectively. 3 patients in CRi died before platelet engraftment. Engraftment rate of platelet within 60 days after allogeneic HSCT was lower for patients in CRi (85% vs. 65%, p = 0.093). To assess the effect of delayed engraftment, we examined infectious events, including bacteria, fungus and virus, within 60 days after allogeneic HSCT. Significantly more patients in CRi had higher cumulative infectious events (46% vs. 72%, p = 0.0086) (Figure 2). There was no bleeding event within 60 days after allogeneic HSCT. Multivariate analysis demonstrated that CRi was an independent risk factor of early infection after allogeneic HSCT (hazard ratio: HR 2.65, 95% CI: 1.37-5.08, p = 0.0037) without a difference in NRM (HR 1.21, 95% CI: 0.26-5.59, p = 0.81). Conclusion: Our data, although retrospectively collected, show that incomplete blood count prior to allogeneic HSCT is a predictable marker of early infection after HSCT in patients with AML. This suggests that we need to develop prophylactic strategies for early infection after allogeneic HSCT based on risk assessments. Disclosures Maeda: Mundipharma KK: Research Funding.

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