Complex Karyotype Predicts Outcome Better Than Monosomal Karyotype In Patients with MDS/Secondary Acute Leukemia Treated with Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): a Retrospective Survey on Behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Abstract Abstract 578 Introduction Monosomal Karyotype (MK) has been shown to be associated with a very poor prognosis in AML patients. Last year at ASH, we presented data from the EBMT on patients diagnosed with MDS and chromosome 7 abnormalities, showing that MK predicts better than complex karyotype (CK) for a dismal outcome after allogeneic HSCT (abstract #293). We now performed a retrospective analysis on data from the registry in the complete cohort of patients with MDS and secondary AL (sAL) to determine the effect of MK on outcome after allogeneic HSCT. Methods A total of 1689 patients from 172 centres in 23 countries with diagnosis MDS or secondary acute leukemia (sAL) with known cytogenetic abnormalities (karyotype only) at diagnosis or later in the disease course were assessed. 1437 were included in the analysis; 226 were excluded because of insufficient data. Kaplan-Meier survival curves were used and log rank test to determine statistical significance. Results 1041 patients were diagnosed with MDS and 396 with sAL. Median follow up for sAL patients was 7.5 months (range 0–253) and MDS 8.0 months (range 0–276). 201 patients fulfilled criteria for MK and 279 patients for complex karyotype (CK). MK outcome was worse than no MK: overall survival 32 months versus 97 months (p=0.002). CK outcome was worse than no CK: overall survival 26 months versus 100 months (p<0.0001). No difference in outcome between MK and CK existed: overall survival of 32 months and 26 months respectively (p= 0.274). There was considerable overlap between MK and CK (i.e. patients fulfilling criteria both for MK and CK). To see how we could further differentiate, we analyzed three subgroups: MK but not CK (43 patients; MK+CK−), no MK but CK (98 patients; MK−CK+) and MK and CK (150 patients; MK+CK+). The survival of patients in each of these groups was compared with the group having no MK and no CK (n=1050). Overall survival was not different for patients with MK+CK− (median 13 vs 19 months, p=0.983), but for patients with MK-CK+ or MK+CK+ a significant difference in survival was observed with a median of 8 months (p=0.008) and 7 months (p< 0.0001) respectively. MK−CK+ and MK+CK+ did not differ statistically (p=0.42) from each other. See figure. These results differ from the results presented at ASH last year. Since this cohort consists of patients with and without chromosome 7 abnormalities, we suspect that presence of this specific chromosomal aberration is the main reason for the observed difference. Multivariate analysis will be performed the coming months. Conclusion These results indicate that CK is a better predictor for poor outcome than MK after allogeneic HSCT in this cohort of MDS and sAL patients with and without chromosome 7 abnormalities. Disclosures: No relevant conflicts of interest to declare.

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A Complex Karyotype but Not Monosomy 7 Is an Independent Prognostic Factor in Advanced Childhood MDS.

Blood ◽

10.1182/blood.v110.11.2452.2452 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2452-2452

Author(s):

Gudrun Gohring ◽

Kyra Michalova ◽

Berna Beverloo ◽

David Betts ◽

Jochen Harbott ◽

...

Keyword(s):

Chromosome Aberrations ◽

Conflicts Of Interest ◽

Bone Marrow Failure ◽

Prognostic Significance ◽

Complex Karyotype ◽

Similar Frequency ◽

Hematopoietic Stem ◽

Monosomy 7 ◽

Significant Difference ◽

Secondary Mds

Abstract Disclosure: No relevant conflicts of interest to declare. To study the clinical significance of recurrent chromosome aberrations in childhood MDS, cytogenetic data of 394 consecutive children with refractory cytopenia (RC) (N=215), RAEB (N=141) and RAEB-T (N=38) analyzed in the regional cytogenetic reference centers and registered in the prospective study EWOG-MDS 98 between 1998 and 2005 were evaluated. At diagnosis, a karyotype could be defined in 279/394 patients (pts) (71%). No karyotype was obtained in 16% of pts with RC compared to 8% pts with RAEB and RAEB-t (p<0.001). Clonal chromosome aberrations were more common in pts with advanced MDS (RAEB and RAEB-T, 61%) compared to RC (29%), and in pts with secondary (69%) compared to primary MDS (36%) (p<0.001). Monosomy 7 was the most frequent aberration occurring with similar frequency in RC (47% of abnormal karyotypes) compared to advanced MDS (49%) and in primary (53%) compared to secondary (41%) MDS. In addition, aberrations typical for de novo AML such as aberrations involving 11q23 or 3q, t(6;9) and del(9q) were noted in morphologically and clinically unequivocal MDS cases. Recurrent aberrations of adult MDS like isolated del(5q), del(20q) and -Y were very uncommon indicating a different pathogenesis of these cases. In pts with advanced MDS, there was no significant difference in overall survival (OS) of pts with normal karyotype (44% ± 18) compared to pts with monosomy 7 (58% ± 19) and patients with other karyotypes (61% ± 22). However, pts with advanced MDS and a complex karyotype (defined by ≥ 3 chromosome aberrations, presence of structural aberrations and excluding clonal evolution of monosomy 7) had a shorter OS (16% ±15, p<0.01). OS and event-free survival after hematopoietic stem cell transplantation (HSCT) in pts with complex karyotypes was inferior compared to that of pts with other cytogenetic aberrations (p=0.012 and 0.039, respectively). Within the group of pts with secondary MDS, complex karyotypes were found in MDS evolving from inherited bone marrow failure disorders or after radio-/ chemotherapy, but absent in familial MDS and cases evolving from acquired aplastic anemia. As shown in a multivariate Cox analysis, advanced MDS, secondary MDS, the presence of a complex karyotype and HSCT were identified as independent prognostic factors for OS. Thus, this study demonstrates the prognostic significance of cytogenetic findings in advanced childhood MDS independent of HSCT.

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Impact of Rapid Lymphocyte and Monocyte Recovery on Overall Survival Post-Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with Fludarabine/Melphalan Conditioning

Blood ◽

10.1182/blood.v118.21.3040.3040 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3040-3040

Author(s):

Lori DeCook ◽

Mary Thoma ◽

Tanya Huneke ◽

Nicole Johnson ◽

Robert Wiegand ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Acute Leukemia ◽

Hematopoietic Stem Cell ◽

Conflicts Of Interest ◽

Positive Impact ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Absolute Lymphocyte Counts ◽

Complete Blood Counts

Abstract Abstract 3040 We have previously shown that both lymphocyte and monocyte recovery are strongly associated with improved survival post-myeloablative allogeneic hematopoietic stem cell transplant for acute leukemia (Thoma et al, Biology of Blood and Marrow Transplantation, in press). We hypothesized that rapid lymphocyte and monocyte recovery would have a similarly positive impact on overall survival in reduced intensity conditioning (RIC) HSCT with fludarabine/melphalan. To test our hypothesis, we analyzed 118 consecutive patients who underwent allogeneic HSCT with fludarabine/melphalan conditioning for AML (n=49) and MDS/MPN (n=38), ALL (n=7) and other lymphoid malignancies (n=24) at our institution from 2001–2010. The absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) derived from routine complete blood counts were determined longitudinally at days +15, +30, +60, +100 and correlated with clinical outcomes. At the day +30 time point, both ALC and AMC > 0.3 × 10(9) cells/L were strongly associated with improved survival (OS 29.6 months vs. 5.4 months, p=0.006 and 25.3 months vs. 5.1 months, p=0.01 respectively), a pattern that continued through the day +100 evaluation. Multivariate analysis including age, CD34+ cell dose, unrelated vs. related HSCT, presence of aGVHD, remission status, and longitudinal hematologic parameters revealed that day +100 ALC (RR 0.21, 95% CI 0.07–0.66, p= 0.0096) and day +100 AMC (RR 0.41, 95% CI 0.2–0.9, p=0.047) were the only independent predictors of survival in the model. Pairwise correlations showed moderate negative associations between aGVHD and day +60 and day +100 ALC and AMC. To further explore whether any inherent patterns in the timing of lymphocyte and monocyte recovery had prognostic value post-HSCT, we performed unsupervised hierarchical clustering on the longitudinal hematopoietic parameters studied in this cohort and identified four clusters of patients, clusters A-D. Patient clusters A and C both demonstrated improved ALC and AMC recovery at the day +60 and day +100 time points and had significantly improved OS compared with clusters B and D (not reached for A and C vs. 54.9 and 22.3 months, respectively, p<0.001). No patient in cluster D had a day +100 AMC > 0.3 × 10(9) cells/L, and these patients experienced more acute GVHD (p=0.006) and relapse (8 of 14 patients, p=0.002) compared with clusters A, B, and C (p=0.002). 29 patients who were unable to be clustered with this algorithm, predominantly due to early toxic deaths, had a median survival of 6 months. Consistent with previous observations in our myeloablative cohort, both lymphocyte and monocyte recovery are predictive of overall survival post-RIC HSCT. However, compared to the myeloablative cohort, monocyte recovery in this series appears slightly less strongly associated with survival. Our results also extend the observation of improved survival of ALC and AMC recovery post-HSCT to diseases beyond acute leukemia. Disclosures: No relevant conflicts of interest to declare.

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A Meta-Analysis of CAG (cytarabine, aclarubicin, G-CSF) Regimen for the Treatment of 1045 Patients with Leukemia in China and Japan,

Blood ◽

10.1182/blood.v118.21.3638.3638 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3638-3638

Author(s):

Guoqing Wei ◽

Wanmao Ni ◽

Dicky Chiao ◽

He Huang ◽

Zhen Cai ◽

...

Keyword(s):

Acute Leukemia ◽

Fixed Effects ◽

De Novo ◽

Conflicts Of Interest ◽

Meta Analysis ◽

Early Death ◽

Newly Diagnosed ◽

Significant Difference ◽

China And Japan ◽

Better Than

Abstract Abstract 3638 Background: CAG regimen (cytarabine, aclarubicin, G-CSF) has been commonly used in China and Japan for the treatment of AML and MDS. This study is to summarize the data and to analyze the efficacy as well as the toxic effects of CAG regimen in acute leukemia (AL) and MDS pts. Methods: The databases of PubMed, Wanfang Data, as well as American Society of Hematology (ASH) annual meeting abstracts were searched for articles published in English, Chinese and Japanese languages between January 1995 and December 2010. Eligible studies were relevant clinical trials on AL and MDS pts treated with CAG regimen. Complete remission (CR) rates and odds ratio (OR) were compared through a meta-analysis using a random-effects or fixed-effects model. Results: 37 trials with a total of 1045 AL and MDS pts were included for analysis. Among the 1045 pts treated with CAG, 819 pts were AML, 215 pts were de novo MDS or transformed AML (MDS/tAML), 6 pts were ALL, and 5 pts were biphenotypic acute leukemia (BAL). The AML CR rate of CAG from 29 studies was 58.0% (95% CI, 53.1%-62.7%). The MDS/t-AML CR rate from 12 studies was 45.7% (95% CI, 39.0%-52.4%). The AML CR rate was significantly better than that of MDS /tAML (Q=8.072, p<0.01). Among 819 AML pts, 327 pts were newly diagnosed, 370 pts were relapsed/refractory (R/R) AML. The AML status was not specified in the rest 122 pts. Interestingly, no significant difference in CR rates was noted between the newly diagnosed (57.0%, 95% CI 51.5%-62.3%) and R/R AML pts (60.1%, 95% CI 50.5%-68.9%) (Q=0.312, p>0.05). The CR rate for the 367 elderly AML pts was 52% (95% CI 51.5%-62.3%). The CR rate was also significantly higher in pts with favorable (64.5%, 95% CI 38.8%-83.9%) and intermediate (69.6%, 95% CI 60.4%-77.5%) cytogenetics than those with unfavorable one (29.5%, 95% CI 19.7%-41.8%) (p<0.05). There were 7 trials that compared the CR rates of CAG regimen with those of other induction regimens in AML pts. Surprisingly, the CR rate of CAG was significantly higher than those of other induction regimens (OR 2.425, 95% CI, 1.515–3.880). CAG regimens were well tolerated with cardiotoxicity in 0.42% cases (4/954) and early death occurred in 4.40% cases (44/1000). Conclusions: CAG regimen induced significantly higher CR rates in AML than in MDS pts. The CR rates of CAG regimen was significantly better than those of other induction regimens in AML pts. This regimen was well tolerated with low cardiotoxicity and early death rate. Disclosures: No relevant conflicts of interest to declare.

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Patients with Monosomal Karyotype in Acute Myeloid Leukemia Is Prognostically Worse Than with Complex Karyotype

Blood ◽

10.1182/blood.v118.21.4735.4735 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4735-4735

Author(s):

Liu Xiaoli ◽

Xu Na ◽

DU Qingfeng ◽

Xu Dan ◽

Meng Fanyi ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Confidence Interval ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Disease Free Survival ◽

Structural Abnormality ◽

Complex Karyotype ◽

Significant Difference ◽

Monosomal Karyotype ◽

Acute Myeloid

Abstract Abstract 4735 Purpose: Monosomal karyotype (MK) refers to the presence of two or more distinct autosomal monosomies or a single monosomy associated with a structural abnormality. To analyze the prognosis of cytogenetic components of a complex karyotype or Monosomal Karyotype in acute myeloid leukemia (AML) except acute promyelocytic leukemia(APL). Patients and Methods:Cytogenetics and overall survival (OS), Disease free survival(DFS) were analyzed in 551 AML patients age 14 to 60 years in our center.Results: There ware 235 patiets with cytogenetic abnormalities, 25 cases with inv(16)(p13.1q22) or t(16;16)(p13.1;q22),and 63 cases with t(8;21); 31 cases (13.2%)met the criteria for MK and 39 cases (16.6%) had a complex karyotype without monosomies. OS was significantly inferior in patients with MK compared with those with a complex karyotype without monosomies (P<0.01;HR 1.85,95% confidence interval(95%CI),0.95-2.81). There was no difference between MK cases with complex karyotype cases in DFS (P>0.05□GHR 3.42,95% confidence interval(95%CI),2.96-6.70). There was significant difference in regardless of whether OS or DFS between MK+ patients with MK− patients (P<0.01). Conclusion: MK was one of independent risk factor in AML patients. Disclosures: No relevant conflicts of interest to declare.

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Chromosomal Instability: A Probable Unfavorable Prognostic Factor For Patients Of Myeloidysplastic Syndromes

Blood ◽

10.1182/blood.v122.21.5243.5243 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5243-5243

Author(s):

Yajuan Xiao ◽

Yuanlu Huang ◽

Na Xu ◽

Rong Lin ◽

Xuan Zhou ◽

...

Keyword(s):

Chromosomal Instability ◽

Chromosomal Abnormalities ◽

Conflicts Of Interest ◽

Normal Karyotype ◽

Chromosome 7 ◽

Complex Karyotype ◽

Karyotypic Analysis ◽

Hematopoetic Stem Cell ◽

Significant Difference

Abstract Objective Myelodysplastic syndromes (MDS) are a group of heterogeneous hematopoetic stem cell clonal disorders with a high frequency of karyotypic abnormalities (40-60%). Among karyotypic abnormalities, abnormal chromosome numbers (aneuploidy) occurs frequently. In aneuploidy, chromosomal instability (CIN) is defined as persistent mis-segregation of whole chromosomes and is caused by defects during mitosis with an odd number of chromosomes. CIN is associated with tumor heterogenesis, multidrug resistance and aggressiveness in solid tumor. Hence, we performed a one-center study on MDS patients to uncover the role of CIN in MDS clinical development. Method A total of 104 cases , 62 male and 42 female, aged from 15 years to 89 years, were tested by fluorescent in situ hybridization (FISH) and karyotypic analysis before any therapeutic intervention. According to the cytogenetic analysis of those two technology they were separated into 5 groups including: CIN, normal karyotype, complex karyotype excluding CIN, deletion chromosome 7 abnormality and other chromosomal abnormalities. All cases were followed up for a median of 19.5 months. Results Karyotyping and FISH identified 70 (67.3%) patients with abnormal karyotypes containing 32 cases of CIN, 9 cases of deletion chromosome 7 abnormality and 5 cases of complex karyotype excluding CIN. The median survival for CIN group was 13 months (incredible interval:6-20 months) compared with 23 months (incredible interval :20-27 months) in all cases, 44months in normal karyotype, 23 months in deletion chromosome 7 abnormality and 13 months in complex karyotype excluding CIN group (P=0.001 for log rank method). In CIN group, 11 cases transformed into acute leukemia with a incidence of 34% with no significant difference with total cases. And the length of time for leukemia transformation shows no significant difference between CIN group and total cases. Conclusion Chromosomal instability in MDS patients of the study revealed worst prognosis compared with other groups. This may suggest that chromosomal instability in MDS chromosomal abnormality confer a significant independent adverse impact on patients survival. However this effect might have no relation to leukemia transformation. Disclosures: No relevant conflicts of interest to declare.

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Colony-Forming Unit Cell (CFU-C) Assays in Myelodysplastic Syndrome

Blood ◽

10.1182/blood.v126.23.2874.2874 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2874-2874

Author(s):

Bing Li ◽

Jinqin Liu ◽

Shiqiang Qu ◽

Robert Peter Gale ◽

Ruixian Xing ◽

...

Keyword(s):

Overall Survival ◽

Scoring System ◽

Conflicts Of Interest ◽

Unit Cell ◽

International Prognostic Scoring System ◽

Hematopoietic Stem ◽

Colony Forming Unit ◽

Significant Difference

Abstract Introduction: The myelodysplastic syndromes (MDS) are a group of clonal diseases derived from hematopoietic stem cells (HSC). Colony-forming unit cell (CFU-C) assay is an effective method to study the number and the function of HSC in vitro. In this study, we focus on the characteristics and the prognostic value of CFU-C in patients with MDS. Patients and Method: CFU-C assays were performed according to the protocol of MethoCultTM H4435 Enriched (STEMCELL Technologies). A colony was defined as an aggregate of >40 cells. Clusters consisted of 4 to 40 cells. 560 consecutive newly-diagnosed, untreated subjects with MDS diagnosed from March, 2001 to April, 2013 were studied. All subjects were reclassified according to the 2008 WHO criteria. 535 subjects with evaluable cytogenetics were classified using the International Prognostic Scoring System (IPSS) and the revised International Prognostic Scoring System (IPSS-R) criteria. Follow-up data were available for 470£¨84%£©subjects. Median follow-up of survivors was 26 months (range, 1-170) months. Subjects receiving an allotransplants were censored in survival analyses. Erythroid and myeloid colonies were isolated from each subject with one cytogenetic abnormality such as del(5/5q-) or +8. Cytogenetic abnormalities of each colony were analyzed by fluorescence in situ hybridization (FISH). SPSS 17.0 software was used to make statistical analysis. Results: Frequencies of burst-forming units-erythroid (BFU-E), colony forming unit-erythroid (CFU-E) and colony forming unit-granulocytes/macrophages (CFU-G/M) were significantly lower than normals (P<0.05) (Table 1). Subjects classified as lower risk in IPSS and IPSS-R had significantly higher numbers of BFU-E and CFU-E (P<0.05) but similar numbers CFU-G/M and clusters-G/M compared with higher risk subjects (Table 2). In 11 subjects with del(-5/5q-) or +8 identified by G- and/or R-banding, both normal and abnormal CFU-Cs were identified in 8 subjects studied by FISH. A high ratio of cluster- to CFU-G/M (>0.6) was associated with poor-risk cytogenetics (Table 2) and with worse overall survival in univariable (Figure 1, P=0.001) and multivariable analyses (HR 1.748, [1.01-3.0]; P=0.046) after adjusting for IPSS. Conclusions: These data suggest abnormalities of proliferation and differentiation of erythroid and myeloid precursor cells in vitro parallel the ineffective hematopoiesis typical of MDS and may be useful in predicting outcomes of patients with MDS. Table 1. CFU-C in MDS subtypes N BFU-E CFU-E CFU-G/M N Ratio of cluster- to CFU-G/M RA 21 8 (0-44) 40 (0-134) 14 (0-127)1 6 0.25 (0.40-1.00) RT 4 18 (4-55) 75 (60-90)1 30 (18-70)1 2 2 RARS 27 12 (0-33) 35 (1-140) 12 (0-70)1 10 0.45 (0.17-0.80) RCMD 275 10 (0-80) 33 (0-178) 14 (0-100) 126 0.35 (0-0.83) RAEB1 112 10 (0-258) 32 (0-312) 14 (0-89) 53 0.47 (0-1.00) RAEB2 103 9 (0-46) 25 (0-120) 13 (0-72) 42 0.37 (0-1.00) MDS-U 15 4 (0-58) 25 (0-161) 10 (0-43) 3 2 Del(5q) 3 2 (2-4) 15 (0-20) 5 (5-41)1 1 2 1No significant difference compared with normals. 2Too few cases to analyze. Table 2. Associations between CFU-C and clinical and laboratory variables N BFU-E P CFU-E P CFU-G/M P Number Ratio of cluster- to CFU-GM P IPSS 0.064 0.006 0.361 0.089 Low 30 13 (0-44) 60 (0-169) 19 (0-45) 10 0.44 (0.24-0.70) Int-1 361 10 (0-258) 33 (0-312) 14 (0-127) 150 0.33 (0-1.00) Int-2 115 9 (0-61) 30 (0-137) 14 (0-72) 52 0.45 (0-1.00) High 29 7 (0-34) 21 (0-93) 12 (0-67) 12 0.44 (0-1.00) IPSS-R 0.003 0.003 0.125 0.209 Very low 7 16 (9-25) 30 (15-120) 18 (5-33) 2 0.29 (0.10-0.49) Low 130 14 (0-80) 42 (0-178) 17 (0-70) 48 0.31 (0-0.77) Intermediate 173 10 (0-66) 34 (0-161) 13 (0-127) 81 0.37 (0-1.00) High 139 9 (0-259) 29 (0-312) 11 (0-89) 51 0.33 (0-1.00) Very high 86 8 (0-61) 25 (0-137) 14 (0-91) 42 0.47 (0-1.00) Cytogenetics (IPSS) 0.867 0.055 0.290 0.007 Good 327 10 (0-258) 36 (0-312) 15 (0-89) 133 0.33 (0-1.00) Intermediate 133 10 (0-69) 30 (0-162) 12 (0-127) 63 0.45 (0-1.00) Poor 75 10 (0-61) 25 (0-137) 14 (0-91) 28 0.42 (0-1.00) Cytogenetics (IPSS-R) 0.990 0.090 0.676 0.022 Very good 7 11 (4-20) 48 (1-110) 14 (8-28) 2 0.49 (0.43-0.56) Good 324 10 (0-258) 35 (0-312) 15 (0-89) 132 0.33 (0-1.00) Intermediate 129 10 (0-69) 30 (0-162) 12 (0-127) 62 0.45 (0-1.00) Poor 27 10 (0-61) 35 (0-137) 16 (0-48) 8 0.36 (0.15-1.00) Very poor 48 11 (0-42) 22 (0-120) 14 (0-91) 20 0.53 (0-1.00) Figure 1. Overall survival in subjects with cluster- to CFU-G/M ratios ¡Ü or > 60%. Figure 1. Overall survival in subjects with cluster- to CFU-G/M ratios ¡Ü or > 60%. Disclosures No relevant conflicts of interest to declare.

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Validation of the EBMT Risk Score for Patients with Hematologic Malignancies Receiving Allogeneic Hematopoietic Stem Cell Transplant in a Transplant Center in Colombia over 20 Years

Blood ◽

10.1182/blood.v126.23.5542.5542 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5542-5542

Author(s):

Virginia Abello ◽

Carmen Rosales ◽

Manuel Rosales ◽

Javier Figueroa ◽

Iris Cordoba ◽

...

Keyword(s):

Overall Survival ◽

Latin America ◽

Risk Score ◽

Conflicts Of Interest ◽

Risk Groups ◽

Hematologic Malignancies ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Significant Difference

Abstract INTRODUCCION EMBT the risk score has been validated in several studies in different types of diseases and modalities of transplantation. The conditions of the patients and the resources available in Latin America are different from those of European centers, so we consider important to validate this scale in our own patients. METHODS EBMT risk scale was validated in 965 of 1176 (750 autologous, allogeneic 426) transplanted from 1993 to 2014; that had all the information available and were not lost to follow up. Kaplan-Meier survival curves and log-rank test (p <0.05) were used to estimate the one (OS1) and three (OS3) probabilities of overall survival according to risk groups. RESULTS The mean age was 39.8 (SD 15.5). The median follow-up was 363 days (range: 179-1096) for the whole group. Most frequent diagnoses were Non-hodgkins lymphoma (314: 26.7%) and multiple myeloma (262: 22.22%). 96.3% transplants were performed using peripheral blood stem cells. Most donors were identical siblings; only 19.5% (n = 79) were transplanted before 2004. 81.9% of transplanted patients had 2-4 points on EBMT risk score. Upon analysis it became clear that at 1 and 3 years, two groups were defined: Low (0-3 points) and high (4-7), with a significant difference in overall survival for AML (1 year: p = <0.00; 3 years: p = <0.00) and ALL (1 year: p = 0.04; 3 years: p = 0.01). In NHL 4 risk groups remain significantly different in regards to 1 and 3 years overall survival (1 year: p = 0.04; 3 years: p = 0.02). In patients with diagnosis of MDS EBMT was predictive of survival only significant at one year (p = 0.01). The EBMT score did to delineate risk groups patients with MM, LH, ASMO, or CML in this group. CONCLUSION EBMT score was validated in patients with hematologic malignancies transplanted in a center in Colombia, to our knowledge this is the first validation of this risk score in Latin America. Disclosures No relevant conflicts of interest to declare.

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The Majority of Patients Receiving Donor Lymphocyte Infusions for Relapsed Chronic Myeloid Leukemia Remain PCR Positive Despite Maintaining Long-Term Remission,

Blood ◽

10.1182/blood.v118.21.4103.4103 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4103-4103 ◽

Cited By ~ 2

Author(s):

Andrew J Innes ◽

James Lurkins ◽

Richard M Szydlo ◽

Andrea Guerra ◽

Dragana Milojkovic ◽

...

Keyword(s):

Conflicts Of Interest ◽

Molecular Remission ◽

Hematopoietic Stem ◽

Low Level ◽

Survival Difference ◽

Significant Difference ◽

Positive Results ◽

Donor Lymphocyte Infusions ◽

Better Than

Abstract Abstract 4103 Donor lymphocyte infusions (DLI) produce molecular remission in the large majority of chronic myeloid leukaemia (CML) patients who relapse after allografting. Although response to DLI is associated with long-term clinical remissions, we asked whether minimal residual disease could still be detected. We identified 116 patients who had received escalating doses of donor lymphocytes between 1995 and 2010 for molecular, cytogenetic or haematological relapse following allogeneic hematopoietic stem cell transplantation for CML. These patients had serial monitoring of their response by quantitative reverse transcriptase–polymerase chain reaction (RT-PCR). 84 patients had achieved a complete molecular remission (CMR) (defined by 2 consecutive negative PCR), however 79 (94%) of these subsequently became positive again. All patients who achieved a complete molecular remission were allocated to 3 categories: (1) “persistently negative” or a single low level positive result (n=15 (18%); (2) “fluctuating low-level positive”, who had multiple positive results, but never more than 2 consecutive positive results (n=34 (40%)); and (3) “persistently low-level positive” (n=35(42%)), and the rates of relapse were compared in the three groups. The overall probability of relapse (defined by the initial molecular relapse criteria) at 10 years was low in all three groups (6.7%), and there was no significant difference in each category: 0%, 4.2% and 10.3% respectively (P=0.372) (figure 1), with no survival difference in the three groups. Furthermore, of the 32 patients who did not achieve a CMR, 11 achieved a fall in PCR to <0.1 (major molecular remission (MMR)) following completion of their DLI protocol and had a non-inferior survival to those who achieve a CMR, in contrast to those who did not satisfy either of these criteria, and had a significantly inferior survival (p<0.01) (figure 2). We conclude that the majority of patients who respond to DLI do not remain PCR negative, but low-level positive results do not predict relapse. This suggests that, although DLI does not completely eradicate the disease, it exerts a highly effective long-term disease control. The data presented also raises the question of whether persistent PCR negativity should be unequivocally pursued, or whether a threshold of MMR may be adequate.Figure 1.The probability of molecular relapse following complete molecular remission is low and not significantly different between those who are persistently negative, fluctuating low-level positive or persistently positive.Figure 1. The probability of molecular relapse following complete molecular remission is low and not significantly different between those who are persistently negative, fluctuating low-level positive or persistently positive.Figure 2.Patients who achieve a major molecular remission but not a complete molecular remission have non-inferior survival to those who do achieve a complete molecular remission, which is significantly better than those who do not achieve either of these.Figure 2. Patients who achieve a major molecular remission but not a complete molecular remission have non-inferior survival to those who do achieve a complete molecular remission, which is significantly better than those who do not achieve either of these. Disclosures: No relevant conflicts of interest to declare.

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Time from Relapse to Donor Leukocyte Infusion in Allogeneic Stem Cell Transplantation Patients Is Longer for Recipients of Unrelated DLI Compared to Matched Sibling DLI, with Similar Incidence of Graft Versus Host Disease (GVHD) and Survival

Blood ◽

10.1182/blood.v124.21.3946.3946 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3946-3946

Author(s):

Anita J. Kumar ◽

Pavel Vassilev ◽

Alison W. Loren ◽

Selina M. Luger ◽

Ran Reshef ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Acute Leukemia ◽

Median Time ◽

Time Interval ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Allogeneic Hct ◽

Donor Leukocyte Infusion ◽

Significant Difference

Abstract Donor leukocyte infusion (DLI) can induce potent graft-versus-leukemia (GvL) activity in patients with relapsed acute leukemia after allogeneic hematopoietic stem cell transplant (HCT), but outcomes are generally poor, with high disease-related mortality. There is little data comparing logistics and outcomes of unrelated (uDLI) versus sibling (msDLI) DLI for relapse after allogeneic HCT. We performed a single-center retrospective cohort study to assess differences in time to obtain DLI from unrelated versus sibling donors, and to compare outcomes from both populations between 2000-2011. Fifty-three patients had relapsed AML, ALL, or high-risk MDS after allogeneic HCT from 2000-2011 at the University of Pennsylvania. Median time from relapse to infusion administration was 56 days for uDLI and 40 days for msDLI patients (p=0.034). However the time from DLI request to infusion was not significantly different between groups (27 days for uDLI and 40 days for msDLI, p=0.20) implying that the longer time from relapse to DLI was due to a longer time interval to request DLI from an URD. 29/35 msDLI patients and 10/18 uDLI patients received chemotherapy prior to DLI. Administration of chemotherapy did not significantly affect time from relapse to DLI (msDLI p=0.26, uDLI p=0.71). 15/35 (43%) of msDLI patients and 8/18 (44%) developed acute GVHD (p=0.91). There was no significant difference in development of IBMTR Grade C/D GVHD among uDLI (29%) and msDLI (24%) patients, p=0.38. The overall survival for the entire group was 96 days with no significant difference between recipients of uDLI and msDLI (p=0.49). Median time to death post DLI was 95 days for uDLI and 97 days for msDLI patients (see Figure I). Death was primarily from disease (74%). At 1 year after DLI, 7/35 (20%) recipients of msDLI were alive and 3/18 (17%) recipients of uDLI were alive (p=0.54). For those patients with response to DLI (defined as improved chimerism, morphologic response, or hematologic response), median time to progression was 68 days in uDLI recipients and 167 days in msDLI recipients (p=0.38). For patients with relapsed acute leukemia and MDS after allogeneic HCT, the time from relapse to DLI was longer for recipients of uDLI compared to msDLI largely due to a longer time from relapse to DLI request. Once requested, there was no significant difference in time from request to infusion, implying this delay to not have an adverse impact on outcome of uDLI compared to MSDLI. Furthermore there was no difference in incidence of GVHD, relapse-free survival, or overall survival after uDLI versus msDLI. Outcomes unfortunately remain poor regardless of donor source. Our data support ongoing investigational efforts to improve outcomes for DLI recipients and overall supports feasibility of using both uDLI and msDLI in future studies. Figure 1 Figure 1. p=0.49 Disclosures No relevant conflicts of interest to declare.

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Comparison of the DONOR Lymphocyte Infusion and Second Allogeneic STEM-CELL Transplantation in the Treatment of First Hematological Relapse after Allogeneic STEM-CELL Transplantation in Adults with ACUTE Leukemia

Blood ◽

10.1182/blood-2019-121599 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5698-5698

Author(s):

Haluk Demiroglu ◽

Elifcan Aladag ◽

Nelson J. Chao ◽

Yahya Buyukasik ◽

Hakan Goker

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Acute Leukemia ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Donor Lymphocyte Infusion ◽

Hematopoietic Stem ◽

Significant Difference

Purpose: Relapse after allogeneic hematopoietic bone marrow transplantation (AHSCT) in acute leukemia is a poor prognosis indicator. Although there is no definite opinion about the optimal treatment chemotherapy, second allogeneic hematopoietic stem cell transplantation (AHSCT2) or donor lymphocyte infusion (DLI) are among the treatment options. Relapse after allogeneic transplantation remains unfortunately quite common and we frequently face difficult management decisions. The decision to offer either option is based on several factors, including donor availability, remission status, presence of disabling comorbidities, and center or physician preference. The aim of this study was to investigate the effect of AHBMT2 or DLI on survival in relapsed transplant patients suffers from acute leukemia. Method:We here in report a retrospective analysis of single-center experience with AHBMT2 and DLI to treat patients relapsing from acute leukemia after a first AHBMT from 2003 to 2018.We enrolled the study 20 patients who underwent DLI and 6 patients who underwent AHBMT2. Result:There was no significant difference in OS between the groups afterward intervention (p:0,9) The 2-year survival rate was 33% in the AHBMT2 group and 43% in the DLI group. After intervention, chronic GVHD was observed only in DLI group. Conclusion: DLI can be considered after relapse as a safer and less toxic method than AHBMT2. Disclosures No relevant conflicts of interest to declare.

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