Abstract 3111
Cord blood transplantation (CB-T) is increasingly used as a treatment alternative for hematological malignancies. The use of double CB-T has leaded to interesting results in adult ...patients. We retrospectively evaluated 31 patients, 19 males and 12 females with a median age of 36 years (range: 20–63) who received double CB-T for hematological malignancies at our institution between 2005 and 2011. There were 15 AML, 9 ALL, 2 CML, 1 Hodgkin disease, 1 NHL, 1 MM and 1 MDS; at transplantation, 18 (58%) were in CR, 5 (16%) in PR and 8 (26%) in relapse, 16 patients received a myeloablative conditioning and 15 a reduced intensity one. Different characteristics of both CB units (CBU) are described in Table 1. When considering matching variables between the 2 CBUs and the recipient, for sex matching: in 10 cases, CBUs were both matched with the recipient, in 1 case both mismatched and in 20 cases, only 1 CBU was mismatched with recipient. For ABO compatibility, in 7 cases, CBUs were both compatible with the recipient, in 13 cases both were incompatible and in 1 case, only one was incompatible. For HLA matching, in 18 cases, both CBUs were 4/6 with the recipient and in 13 cases, only one CBU was 5/6. When considering HLA matching between the 2 CBUs, there were 7 with 3/6 HLA matching, 17 with 4/6, 6 with 5/6 and 1 with 6/6. After transplantation, 25 (81%) patients engrafted among them, 6 had mixed chimerism (presence of the 2 CBUs) and 19 had one dominant CBU. Non-engrafted patients were in relapse or progressive disease and received RIC before allo-HSCT. There were 13 patients who developed acute GVHD ≥2 (8 grade III-IV) and 6 chronic GVHD (3 limited and 3 extensive). After a median follow-up of 6.5 months (range: 1–54), the median OS was not reached with a 1 year probability of 58% (95%CI: 42–80), only 3 patients relapsed. The cumulative incidence of transplant related mortality (TRM) was 37% (95%CI: 28–46). A multivariate model that studied the different matching possibilities (sex, ABO and HLA) between the 2 CBUs together and then between the 2 CBUs with the recipient combined to CNT and CD34 cells number, showed that only the sex matching between the 3 partners can determine the dominant CBU later (p=0.04). In multivariate analysis taking into account pre-transplant and the matching variables, no factor impacted the engraftment while factors that impacted on OS were age HR=1.1 (1.03–1.25), p=0.01, disease status at HSCT relapse, HR=8.7 (1.4–52), p=0.01 and TNC number HR=0.99 (0.98–1), p=0.02. Age and TNC number also had a significant impact on TRM HR=1.12 (1.02–1.23), p=0.01 and HR=0.99 (0.98–1), p=0.003.
In conclusion, we did not find any impact of the different matching variables between the 2 CBUs either together or with the recipient on different transplantation outcomes. Nevertheless, sex matching between the 3 partners seems to play a role in the determination of the dominant CBU later and its installation in the recipient. Display omitted Display omitted
No relevant conflicts of interest to declare.
Abstract 4481
HLA matching has been demonstrated to play a major role in the different outcomes of allogeneic hematopoietic transplantation (allo-HSCT) in patients with hematological malignancies. ...When searching for an unrelated donor the commonly evaluated HLA loci are -A, -B, ± -C, -DRB1 and DQB1. The 2 loci DRB3 and DRB4 have never been taken into account and never been evaluated.
To evaluate the impact of HLA-DRB3 and -DRB4 on the different unrelated allo-HSCT outcomes especially in case of mismatch presence on these loci.
We have of 30 patients (study group) who received unrelated allo-HSCT with a HLA-DRB3 or HLA-DRB4 mismatched donor and we compared their outcomes to outcomes of a matched control group of 30 patients with the same characteristics except for the DRB3 or DRB4 donor mismatching. In the study group, there were 16 males and 14 females with a median age of 45 years (25–62), 18 patients had AML, 6 ALL, 2 MDS, 2 multiple myeloma (MM), 1 CML and 1 NHL. Fifteen patients received a myeloablative conditioning and 15 received a reduced intensity one (RIC). At transplantation, 16 patients were in CR, 4 in PR and 10 in relapse; 15 patients received PBSC and 15 BM. There were 16 patients with 10/10 HLA identical donor among them 11 had a DRB3 mismatch and 5 had a DRB4 mismatch. There were 14 patients with 9/10 HLA identical donor among them 9 had a DRB3 mismatch (mismatched: 3 on HLA-A, 1HLA-B, 4 HLA-C and 1 on HLA-DQB1) and 5 had a DRB4 mismatch (mismatched: 1 on HLA-A, 1HLA-B, 1 HLA-C and 2 on HLA-DQB1). In the control group, there were 16 males and 14 females with a median age of 46 years (25–64), 18 patients had AML, 6 ALL, 3 MM, 1 CML and 2 NHL. Fifteen patients received a myeloablative conditioning and 15 received a RIC. At transplantation, 22 patients were in CR, 1 in PR and 7 in relapse; 15 patients received PBSC and 15 received BM. There were 16 patients with 10/10 HLA identical donor and 14 patients with 9/10 HLA identical donor (mismatched: 6 on HLA-A, 3 HLA-B, 4 HLA-C and 1 on HLA-DQB1) all patients in the control group were matched for HLA-DRB3 and –DRB4.
After HSCT, 27 (90%) patients in the study group engrafted while 29 (96%) engrafted in the control group. The cumulative incidence of acute GVHD≥2 at 3 months was 37% (28–46) and 30% (22–39) for the study and control groups respectively, with a same cumulative incidence of chronic GVHD at one year of 20% (12–28). At day 90 post HSCT, 17 (63%) patients in the study group were in CR and 25 (86%) in CR in the control group. After a median follow-up of 5 months (0.2–46) and 13 months (0.5–60) for study and control groups respectively, the median overall survival (OS) was 7 months (3–32) and 21 months (11-NR) with a 2-years probability of 25% (12–51) and 41% (25–69) respectively; the median time of progression-free survival (PFS) was 3 months (0.2–46) and 10 months (1–60) with a 2-years probability of 16% (6–42) and 37% (21–63) respectively. The cumulative incidence of relapse at 1 year was the same for the two groups with 30% (22–39); the cumulative incidence of transplant related mortality (TRM) at 3 months and 1 year were 17% (10–24) vs. 3% (0–7) and 37% (28–46) vs. 10% (5–16) for study and control groups respectively. The multivariate analysis that studied age, type of disease, matched or mismatched HLA, with or without DRB3 or DRB4 mismatch, disease status at transplantation and type of conditioning showed a significant worse OS in 9/10 mismatched patients with or without a DRB3 or DRB4 mismatch (HR=5.3; 1.6–18 p=0.006); 10/10 matched patients with a DRB3 or DRB4 mismatch (HR=3.9; 1.2–12 p=0.02) and patients not in CR at transplantation (HR= 4.4; 1.6–12 p=0.004); similarly, the same groups had a worse PFS while patients not in CR or with a DRB3 or DRB4 mismatch showed a worse TRM in multivariate analysis, (HR=6; 1.5–24 p= 0.02) and (HR=3.5; 1.02–12 p=0.04) respectively.
We demonstrated that the HLA-DRB3 or DRB4 matching donor is relevant for OS and TRM of patients who undergo allo-HSCT from unrelated donor either in the 10/10 or 9/10 HLA matching settings. Moreover, in view of the important impact of these loci mismatches, we recommend its consideration in the unrelated donor selection setting particularly in the 10/10 HLA unrelated donors. Since the evaluation of these loci is not widely done within HLA laboratories, we suggest conducting a large prospective study in order to validate its impact on unrelated allo-HSCT outcomes. Display omitted
No relevant conflicts of interest to declare.
Abstract 1992
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological malignancies for which umbilical cord blood (UCB) represents an alternative ...source of HSC. In order to overcome the low cellularity of one UCB unit, double (d) UCBT has been developed. The impact of different matching variables between UCB units and recipient including HLA, sex and ABO on the different transplantation outcomes are still unclear and not very well defined yet. On the other hand, a major focus in previous studies has been on cellularity with different thresholds, despite the heterogeneous pre-freezing and post-thawing counting techniques especially without any link to matching variables. In this study, we evaluated the impact of the different matching variables in addition to cellularity and other disease and patient characteristics on single(s) and double UCBT outcomes in pediatric and adult patients between 1998 and 2011. There were 53 adults (37 dUCBT and 16 sUCBT) with a median age of 36 years (18–64) and 48 children (3 dUCBT and 45 sUCBT) with a median age of 2 years (0–14) and a median follow-up of surviving patients of 24 months (1–85). The different patient, UCB, disease and HSCT characteristics have been analyzed and taken into account. The median number of pre-freezing and post-thawing cells was for 1) TNC: 3.3×107/kg (1.9–5.1) and 2.6×107 (1.5–4.6) in adults; 1.6×107 (0.5–4) and 1.18×107 (0.5–3) in children; 2) CD34: 1.89×105 (0.57–4.2) and 1.55×105 (0.5–4.1) in adults; 4×105 (0.6–19.3) and 2.8×105 (0.26–19) in children with a respective cells viability of 54% and 58%. We built a scoring scale that took into account the matching variables (sex, ABO and HLA) between UCB units and recipient and between UCB units each other in case of dUCBT. The median score was 3.8 (1–7) in adults and 3 (1–6) in children; the detailed score calculation method will be communicated later. We evaluated in multivariate analysis separately in adults and children, the impact of the matching score, cellularity, single or double UCBT, type of disease, disease status and conditioning on different HSCT outcomes. We found a positive impact of infused CD34 ≥1.55×105 on neutrophiles recovery in adults HR=2.1 (1.16–3.8), p=0.015 and infused CD34 ≥2.8×105 on neutrophiles and platelets recovery HR=2.5 (1.2–5), p=0.007 and HR= 4.4 (1.6–11.6), p=0.002 respectively in children; no significant factor was observed on the cumulative incidence of acute GVHD≥grade II. In addition, we showed a significant negative impact of matching score > 3.8 on adults overall survival (OS) with a 3 years probability of 19% (6–60) vs. 57% (38–84) for those with score ≤3.8 HR=3.9 (1.5–9.8), p=0.003. Similarly, score >3.8 had a significant negative impact also on progression-free survival (PFS) only in adults with a 3 years probability of 13% (3–65) vs. 21% (5–94) for patients with a score ≤3.8 HR=2.8 (1.01–8), p=0.04. No significant factor was found to influence transplant related mortality.
In conclusion, cell dose remains a significant impacting factor on short term transplantation outcome while the matching score appears to have a strong impact on adult long term outcomes mainly OS and PFS. These very promising results lead us to evaluate this score in larger number of patients for its validation and in order to include it in the UCB unit choice either in simple or double UCBT.
Display omitted
Nicolini:Novartis, Bristol Myers-Squibb, Pfizer, ARIAD, and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
Abstract 4549
Patients with high risk AML have poor outcomes. However, the only approach with curative potential remains allogeneic HSCT. With the aim to improve the effect of allogeneic HSCT by ...sequential use of chemotherapy, RIC regimen and pDLI, we are currently conducting a prospective pilot study for high risk AML. High risk AML was defined by unfavorable cytogenetics, adverse molecular abnormality, secondary AML, and AML requiring 2 induction courses to obtain CR1.
After identification of a HLA 10/10 donor, patients are received the sequential regimen consisted of fludarabine (30mg/m2/d), Ara-c (2g/m2/d) and amsacrine (100mg/m2/d) (FLAMSA) chemotherapy for 4 days. After 3 days of rest, RIC regimen consisted of 4 Gy TBI, cyclophosphamide for 2 days (40 mg/kg in case of matched related donors, and 60 mg/kg for unrelated or mismatched donors), and ATG (5mg/kg total dose) (German regimen) or Busulfan 3.2mg/kg/d during 4 days followed by ATG (5mg/kg total dose) (French regimen). The modified regimen has been established after our results in refractory AML patients (ASH 2011, poster 1957). Prophylactic donor lymphocyte transfusion was given from day +120 in patients who were not receiving immunosuppression and were free of GvHD.
Our objective is to include 20 patients and to compare with a control cohort of patients with the same high risk AML treated according to the conventional strategy during the same period.
Between August 2010 and November 2011, we have included 12 consecutive patients in first complete response who underwent an allogeneic HSCT after sequential FLAMSA-RIC regimen with a median follow-up of 12 months (range 7–22). Nine patients were < 55 years old (median age: 54 28–64), 7 patients had an unrelated donor and 5 patients had a related donor. The stem cell source was PBSC for 11 patients and two cord blood unit for 1 patient. Before FLAMSA-RIC regimen, 3 patients had received two induction courses to obtain CR1. All patients had adverse cytogenetics or molecular abnormalities and 1 patient had a secondary AML.
At the last follow-up, 6 patients (50%) are alive in CR. (Figure 1.) Four patients (33.3%) died in remission. The cause of death was infection for 2 patients, aGvHD for 1 patient and graft failure for 1 patient. Only one patient died from relapse 6 months after transplantation.
Five patients (41.6%) experienced aGvHD and 2 patients (16.6%) had an extensive cGvHD including the patient who has been transplanted with 2 cord blood unit. Six patients (75%) in a group of 8 patients aged > 45 years experienced complications (infection (n=3) and GvHD (n=3)). One patient (25%) from a group of 4 patients aged < 45 years had infectious complication after transplantation. Prophylactic donor lymphocyte transfusion was given in 6 patients, the causes of no administration were GvHD for 2 patients, cord blood unit as stem cell source for 1 patient and 3 patients were dead before 120 days after transplantation. From the 6 patients who had received pDLI, 5 patients are alive in CR and 1 patient died from GvHD.
The FLAMSA-RIC regimen before allogeneic HSCT is a new approach for high risk AML. Between 2012 January and 2012 July, 8 additionnal patients have been included and the results for the whole study will be communicated later. Our primary results are promising especially for young patients (< 45 years) who seem to better profit from this sequential FLAMSA-RIC regimen. Display omitted
Nicolini:Novartis, Bristol Myers-Squibb, Pfizer, ARIAD, and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
Abstract Forty-seven percent of adults with acute myeloid leukemia (AML) who entered the ALFA-9802 trial and achieved a first complete remission (CR) experienced a first relapse. We examined the ...outcome of these 190 adult patients. Eighty-four patients (44%) achieved a second CR. The median overall survival (OS) after relapse was 8.9 months with a 2-year OS at 25%. Factors predicting a better outcome after relapse were stem cell transplant (SCT) performed in second CR and a first CR duration >1 year. Risk groups defined at the time of diagnosis and treatment received in first CR also influenced the outcome after relapse. The best results were obtained in patients with core binding factor (CBF)-AML, while patients initially defined as favorable intermediate risk showed a similar outcome after relapse than those initially entering the poor risk group. We conclude that most adult patients with recurring AML could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option at this stage of the disease.
Abstract 3810
Despite frequent anemia and multiple transfusions during AML chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), recommendations and marketing authorization ...for erythropoietin (EPO) use are still missing. In the current prospective study, as primary objective, we evaluated the effect of EPO on patient's quality of life (QOL). Secondary objective was hemoglobin (Hb) recovery. In addition, a paired matched analysis using similar population was conducted to compare platelets (Pt) and red blood cells (RBC) transfusion number.
We included adult patients with Hb level ≤11g/dl induced by 1, 2 or 3 consolidation chemotherapy for AML in complete remission (CR) (group 1); or by allo-HSCT for any hematological disease (group 2). EPO was administered Sc. once per week during a maximum period of 6 months: for group 1, ARANESP® 150μg; for group 2, NEORECORMON® 30000IU; Hb level was monitored every week. Injections were stopped once the Hb level reached 12g/dl without any transfusion. If after 4 injections, no improvement was observed, doses were doubled, and if after 8 injections, no improvement was observed, patient was taken off-study for EPO inefficiency. The QOL was measured at baseline, at 1, 2, 3 and 6 months by the Functional Assessment of Cancer Therapy–Anemia (FACT–An). EPO responders patients were defined as having Hb level ≥12g/dl (EPO CR) or a ≥ 2g/dl increase EPO partial response (EPO PR) compared with baseline value without any transfusion requirement. The matching analysis took into account: sex, age, disease status, for the two groups, associated to cytogenetics, type of chemotherapy, sequential chemotherapy number for group 1, and diagnosis, conditioning, HSC source, number of previous transplants and GVHD for group 2.
Between April 2006 and December 2009, among 261 screened patients, 55 were included in group1 and 61 in group 2, patient characteristics for each group are summarized in Table1. Main exclusion criteria were EPO contra-indication and patient refusal. The median number of EPO injections/patient was 13 (3 – 24) in group1 and 8 (2 - 28) in group 2. For the global population (111 evaluable patients 52 group1 and 59 in group 2), we have noticed a significant improvement of QOL during the 6 months follow-up according to FACT-An anemia (p=0.01). Despite a non-significant improvement for FACT-G, we observed a significant improvement in physical well-being (p<0.0001). There were 85 EPO CR (83% in group1 and 71% in group 2) and 3 (6%) EPO PR (only in group1). Among patients who reached the 6 months follow-up, 81% had a normal Hb level. Fourteen patients (13%) were withdrawn (6 in group1 and 8 in group 2) due to EPO inefficacy and 9 in group 2 for relapse or EPO related/unrelated serious adverse events (AEs). In group1: the median time to achieve an EPO CR was 34 days (17-67) after first consolidation and 41 days (12-67) after second consolidation (p=0.35). In group 2: the median time to achieve EPO CR was 39 days (14 - 180). After the pair-matched analysis, 44 patients in each group were matched with at least one case-control patient. When comparing RBC and Pt transfusions, there were 712 units and 751 units in the matched population versus 504 and 669 in the EPO population respectively 208 spared RBC (80 in group1, p=0.008 and 128 in group 2, p=0.004) and 100 spared Pt units (all in group1, p=0.001). The multivariate analysis studying different confounding factors on the cumulative incidence of EPO CR showed a significant positive impact of younger age (p=0.001) and intensive chemotherapy (p=0.03) in group1; and for group 2, the positive impact of Pt levels at baseline, the negative impact of female recipient and major ABO incompatibility. We did not find any significant difference in terms of overall (OS) and event free survival (EFS) between EPO and control groups.
This prospective study showed a real benefit of EPO administration on QOL, an achievement of a normal Hb level and a significant spare of RBC and Pt transfusions. Young AML patients, male allo-HSCT recipient, ABO compatible pairs seem to be the best candidates to benefit from EPO administration, with low AEs and no impact on OS or EFS. A cost-effectiveness study is ongoing and results will be communicated.
Display omitted
No relevant conflicts of interest to declare.
Abstract 2954
The serum free light chain (sFLC) analysis has been used for the diagnosis and monitoring of plasma cell dyscrasias and has proved its usefulness in disease treatment response in ...multiple myeloma (MM). Some studies have evaluated the prognostic value of the sFLC levels expressed as K/L ratio (sFLCR) at diagnosis. In contrast, performing this analysis during patient's follow up and on therapy is still not very well defined yet.
Our first objective was to evaluate the impact of sFLCR, measured at diagnosis in MM patients, on the progression free survival (PFS) and overall survival (OS); the second objective was to assess the importance of sFLC analysis during the follow-up especially for relapse/progression detection comparing to concomitant monoclonal-protein (M-p) traditional serum protein electrophoresis (sPE).
Between years 2002 and 2008, we have analysed 174 MM patients for which a concomitant measurement of sFLC and sPE was done during follow-up. Only 118 patients had the sFLCR analysis performed at diagnosis. The sFLC analysis was performed using the Freelite™ test from the Binding site on a BNIIÒ, Dade BehringÓ, and for sPE, analysis was done using a Paragon CZE 2000Ò, Beckman CoulterÓ. There were 92 (53%) males and 82 (47%) females, median age at diagnosis 57 years (34-72), 120 (69%) were IgG (87K&33L), 52 (30%) IgA (41K&11L) and 2 (1%) IgD (1K&1L). According to the ISS, there were 16 (9%) in stage I, 17 (10%) in stage II and 141 (81%) in stage III. Among 61 (35%) FISH analysis done, 31 (51%) detected a chromosome 13 deletion. Twenty six (15%) patients had renal insufficiency. According to the distribution of the different ratios at diagnosis, we have defined three groups: group1 (n=25): patients with 0.13<sFLCR<3.3 which represents the double of the normal range (0.26-1.65); group2 (n=63): patients with sFLCR>3.3 and group3 (n=30): patients with sFLCR<0.13.We also monitored the behaviour of sFLC and sPE in a way to early detect relapse/progression independently of treatment type. Kaplan Meier and cox regression analysis were performed to study the PFS and OS in different groups, slopes of the increase period corresponding to each measurement were compared using the student t-bilateral test with R statistical software.
After a median follow-up of 38 months 3.3-93.7, the 5-years OS for groups 1, 2 and 3 was 75% 56-100, 60% 47-76 and 40% 23-69 respectively; and the 5-years PFS was 69% 49-96, 43% 31-60 and 29% 15-54 respectively. The multivariate analysis studying age, ISS, sex, cytogenetics and sFLCR, showed that both OS and PFS are worslty affected with a more abnormal sFLCR, hazard ratios (HR) in Figure1. After monitoring all patients, we observed 117 (67%) patients with relapse/progression and 57 (33%) patients were still in response to treatment. In 77 (66%) cases, relapse or progression was detected by concomitant increase of both sFLC and the M-p with a significant earlier increase for sFLC (Figure2A). In 17 (15%) patients, the relapse or progression was characterised by the only increase of sFLC without any increase of the M-p (Figure2B). Contrarily, in 5 (4%) patients there was only an increase of the M-p without increasing the sFLC (Figure2D). Finally, in 18 (15%) patients, the relapse or progression was revealed by the increase of M-p faster than the concerned sFLC (Figure2C). When comparing slopes of increasing sFLC to increasing M-p, we found a very high significant difference (p<0.001), thus showing that sFLC have a faster detection of relapse or progression.
Our study has showed that abnormal sFLCR at diagnosis affects OS and more strongly the PFS independently of any other concomitant variable. In 81% of patients, sFLC analysis enabled an earlier detection of relapse/progression compared to sPE, this could be very important for early treatment intervention especially for high risk patients. Since there are no uniform recommendations for the use of this analysis during follow-up, we recommend its concomitant use with sPE, waiting for guidelines and we suggest that the sFLCR at diagnosis deserves more focus for its validation as a prognostic factor in MM.
Display omitted
No relevant conflicts of interest to declare.
Abstract 2371
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) appears to offer a potential advantage in terms of event free survival (EFS) and overall survival (OS) in patients with ...acute leukemia (AL) with bad prognostic factors. The main issue is to find a donor; usually, a patient has 30% chance to find an HLA identical sibling donor (SD) and approximately 40% chance to find a suitable unrelated donor (UD) from international registries. Unfortunately, 40% of registered patients relapse or die before finding a donor.
Our objective was to evaluate the outcome (OS & EFS) in AL patients, whether they had an HLA identical SD, an UD or no donor (ND) after registration on France Greffe de Moelle (FGM) registry, either transplanted later or not. Our secondary objective was to evaluate the impact of interval between, diagnosis and allo-HSCT, donor finding and allo-HSCT, interval registration-allo-HSCT, on OS and EFS.
We have analyzed 251 AL patients diagnosed between January 2000 and December 2008, for whom a search for a donor was initiated for a required allo-HSCT. There were 117 (47%) males and 134 females with a median age at diagnosis of 40 years 16-66, 177 (71%) were AML (prognosis according to cytogenetics & molecular markers: 59 were good, 97 poor and 21 not done) 75 were ALL (prognosis according to cytogenetics & molecular markers: 33 were good, 16 poor and 26 not done). Seventy six (30%) patients had an available SD and received allo-HSCT within a median time of 3.5 months (0.5 – 43) (59 AML & 17 ALL), and 38 (15%) with SD but were not transplanted due to early relapse and/or death. For patients with no available SD, a registration on FGM registry was done. One hundred thirty seven patients were registered after a median interval of 2.3 months (0.4-135) from diagnosis, 33 (13%) patients (24 AML & 9 ALL) did not find any donor, have not been transplanted and they received the standard of care. One hundred and four (41%) patients (62 AML & 42ALL) found an UD or cord blood cell (CBC) unit after a median registration time of 1.6 months (0.3 – 26): 86 with UD of which only 60 have been transplanted within a median time of 2.3 months (0.4 – 14), 18 with CBU of which only 17 were transplanted. Among transplanted patients, 113 (74%) were in complete response (CR) at transplantation, and 40 were in less than CR. Fifty (33%) received peripheral blood (PBSC) (23 UD & 27 SD), 86 (57%) received bone marrow (BM) (37 UD & 49 SD) and 17 (10%) CBC units. For conditioning, 56 (37%) were reduced intensity (29 SD & 27 UD) and 96 standard (47SD & 50 UD). For HLA, there were 45 HLA 10/10, (27BM & 18 PBSC), 14 HLA 9/10 (9BM 5PBSC) 1 HLA 8/10 (BM) and for CBC 14 HLA 4/6 and 3 HLA 5/6.
After a median follow-up of 25 months (0.2- 234), the median OS was 78 months (51 – 133) for transplanted patients with SD (3years OS: 68%), it was 33 months (27 – 47) for transplanted patients with UD (3years OS: 44%), 21 months (15 – 37) for not transplanted patients with available SD or UD (3years OS: 34%) and finally it was 31 months (23-221) for patients with ND (3years OS: 45%). The median EFS for the same groups was 38 months (23 – 133), 24 months (17 – 36), 15 months (11-24) and 23 months (14 – 48) respectively. The only factors negatively affecting OS in multivariate analysis (studying age, sex, AL type, cytogenetics, donor or no donor, transplanted or not, UD or SD) were age and allo-transplanted from UD. When adjusting only on transplanted patients, taking into account in addition to previous factors, the time between diagnosis-registration, time between registration-allo-HSCT, disease status at allo-HSCT, stem cell source, conditioning; three significant factors affected OS: disease status (<CR) HR= 2.8 1.5-5.3 p<0.001; long interval between diagnosis-registration HR= 2 1.2-3.6 p=0.001 and conditioning (standard) HR=0.27 0.1-0.8 p=0.02. (3years OS for SD allo-HSCT, UD allo-HSCT late and early registration: 59%, 29% and 47% respectively).
The results of our first analysis seemed surprising regarding our knowledge of outcome in allo-HSCT from SD and UD, which led us to investigate on unusual interfering factors. We have explored the relation between the interval diagnosis-registration for a donor search and the interval registration-allo-HSCT that appeared as major factors affecting survival in UD allo-HSCT settings.
Display omitted
No relevant conflicts of interest to declare.
Abstract 4336
for patients in search of an unrelated donor for haematopoietic stem cell transplantation (HSCT), a 10/10 allele-matched donor represents the best option; for a CMV- patient, a CMV- ...donor is generally preferred to a CMV+ donor due to low risk of CMV infection when both donor and patients are CMV-, however it is not known at the present how the CMV serological status affects transplant outcome compared to patient-donor HLA matching, and this is particularly true when more than one donor is available. The aim of the present study is to analyze the effect of CMV matching with respect to HLA matching on HSCT outcome, in patients who are CMV-.
CMV-patients who underwent a HSCT from an unrelated donor between 1st Jan 2000 and 31st Mar 2009 at our Institution were included in the analysis. Patients receiving HSC from cord blood were excluded. Evaluation of overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM) and acute graft-versus-host disease (GvHD) were performed with Kaplan-Meier method or cumulative incidence analysis; comparisons among groups were performed using log-rank test. Data about most relevant patients' and donors' factors (patients' age, gender matching, AB0 incompatibility, diagnosis, disease status at HSCT, CMV matching, HLA matching, HSCT conditioning, use of ATG, TBI, source of HSCs) were collected and included in a multivariate Cox regression analysis: the relative impact of CMV and HLA matching on HSCT outcomes were expressed as hazard ratio (HR) together with the 95% confidence interval (CI), after adjustment for the above mentioned factors.
sixty-six patients were eligible for the analysis, median age was 35 (16-64), diagnoses were acute leukemia (n=33: n=23 CR1 and n=10 CR2 or more), MDS (n=8), multiple myeloma (n=8), non Hodgkin's lymphoma (n=6), CML (n=5: n=2 chronic phase, n=3 acceleterated or acute phase), myeloproliferative syndrome other than CML (n=3), aplastic anemia (n=1), CLL (n=1), Hodgkin's lymphoma (n=1). A high-resolution 10/10 HLA matching was present in 55 (83%) HSCTs while one mismatch (9/10-matched donor) was present in 11 (17%) HSCTs: n=8 at HLA-A, n= 3 at HLA-C. All recipients were CMV-. Donors were CMV- in 40 of 55 (73%) 10/10-matched pairs and in 6 of 11 (54%) 9/10-matched pairs. Median follow-up was 225 days (range: 82-2014). In univariate analysis, no significant survival differences were detected among patients with HLA matched and mismatched donors (1y-OS= 42% and 20% respectively, p=0.23) or with CMV- and CMV+ donors (1y-OS= 34% and 48% respectively, p=0.26); no significant differences in occurrence of grade 2-4, grade 3-4 acute GvHD or PFS were observed as well. However, a significantly increased probability of NRM was seen when a HLA mismatched donor was present (1y-NRM= 80% vs 33%, p=0.03); this was not the case of CMV serological status (p=0.31). Multivariate analysis for NRM showed a HR = 5.22 (95% CI: 1.47-18.56) with p= 0.01 for HLA mismatched vs. matched and HR = 0.72 (95% CI: 0.23-2.24) with p= 0.57 for CMV mismatched vs. matched.
these results confirm that HLA matching is critical in determining the incidence of NRM and should continue to be preferred to CMV matching in CMV seronegative patients undergoing HSCT from an unrelated donor. However, a larger, multicenter analysis could better clarify this issue and help to define the relative importance of HLA matching vs. CMV serology in this setting of patients.
No relevant conflicts of interest to declare.
Abstract 4678
Improvement of survival in AML patients remains an important objective to achieve; recently better therapeutic strategies were defined according to the stratification of different ...markers. According to cytogenetics and molecular markers we determined 2 groups of patients: a good prognosis group for patients who had good cytogenetics inv 16 and t (8, 21)and intermediate 1 (normal cytogenetics associated to either NMP1+ with ITD- or CEBPα +ITD-) and a poor prognosis group for patients classified as in intermediate 2 (normal cytogenetics associated to other molecular markers) and unfavourable cytogenetics. To see if allogeneic hematopoietic stem cell transplantation had an impact on these groups, we studied 78 patients who underwent an allogeneic HSCT for AML and for whom we had cytogenetics and molecular markers. There were 73 de novo and 5 secondary AML, FAB classification showed 9 M0, 11 M1, 15 M2, 8 M4, 24 M5, 3 M6, 1M7, 7 patients were unclassified. Regarding cytogenetics and molecular markers: 6 were in favourable, 29 in intermediate and 38 in unfavourable group and we found 5 Flt3 mutated, 22 Flt3 ITD+, 4 MLL mutated, 13 Hoxa9 mutated, 10 Evi1 mutated, 34 Wt1 mutated and 17 NMP mutated. Using the new classification, 11 patients were in the good prognosis group and 61 in the poor prognosis group (6 patients have not been classified due to cytogenetics failure and/or missing data of molecular markers). At transplant, 42 patients were in CR1, 22 in > CR1 and 14 in progressive disease, 49 received a myelo-ablative and 29 a non myelo-ablative conditioning. As HSC source, 27 received PBSC, 46 bone marrow and 5 cord blood cells. At the last follow-up, 28 have relapsed, 38 patients are alive (36 in CR and 2 in relapse) and 40 died. With a median follow-up of 32 months, the 3-years overall survival was 45%±12 with no significant impact of age, FAB classification, kind of AML (de novo vs secondary), HSC source (PBSC vs BM), Flt3, MLL, HoxA9, NMP and WT1 mutations. We found a difference of survival but not reaching the significance for Flt3 ITD 27.5% ±20 (mutated)vs 52% ±12 (non mutated), p=0.09 and a significant difference of survival for Evi1 48.5%±14 (non mutated) vs 22.5% ±26 (mutated), p=0.04. We also showed a difference of survival not reaching the significance according to cytogenetics with 83%±30 for favourable, 53%±20 for intermesiate and 28%±16 for unfavourable although we observed a very significant difference of OS according to the new prognosis classification between the good prognosis group with 81%±24 and the poor prognosis group with 38%±14 (p=0.04). In addition, we found a significant better survival for patients in 1st CR (60%±16) vs > CR1 (31%±22) or in progressive disease (24%±22)(p=0.009) and a significant difference of survival according to conditioning with 54%±16 for myelo-abative vs 11%±18 for RIC ( p<0.0001). But, for patients receiving a nonmyelo-ablative conditioning, we noted that the majority of patients presented poor risk factors with 12 and 13 (86%) among the 29 patients belonging to intermediate and unfavourable cytogenetics groups, 25 (86%) were in poor prognosis and 19 patients (65%) were in progressive disease or in > CR1 at transplant. The multivariate analysis showed a significant impact on OS of the new prognosis classification HR=3.62 95%CI 2.89-4.35 (p=0.03), disease status at transplant HR=151 95%CI 1.28-1.74 (p=0.07), kind of conditioning HR=0.32 95%CI 0-0.7 (p=0.003), Evi1 HR=0.3395%CI 0-0.8 (p=0.02) and Flt3 ITD HR=0.43 95%CI 0.07-0.78 (p=0.02). This study showed the importance of the new prognosis classification in terms of OS for AML and allogeneic HSCT did not erase the impact of this parameter, the OS after allogeneic HSCT remains very poor for patients having Evi1 mutation and Flt3ITD for whom it is fundamental to propose new strategy of allogeneic HSCT in 1st CR as for example allotransplant after FLAMSA regimen or haplo-identical allogeneic HSCT.
No relevant conflicts of interest to declare.
