Clinical impact of the clone size in MDS cases with monosomy 7 or 7q deletion, trisomy 8, 20q deletion and loss of Y chromosome

The clone size has been postulated as a prognostic factor in myelodysplastic syndromes (MDS), though it has not been studied systematically. We tested its impact (<100% vs. 100%) in a population of 216 MDS with chromosome 7 abnormalities (−7/7q−) (n = 84), trisomy 8 (n = 99), 20q deletion (n = 28) and loss of Y chromosome (n = 26). Focusing on the survival the bad prognosis of −7/7q− was independent of the clone size (9.3 vs. 5.0 months, P = 0.188, not significant) but trisomy 8 cases with 100% aberrant metaphases did reveal a worse prognosis (13.9 vs. 5.9 months, P = 0.003).     

Telomere length,c-myc and mad-1 expression could represent prognosis markers of myelodysplastic syndrome

Telomere dysfunction might generate genomic instability leading to the progression of myelodysplastic syndromes (MDS) into acute myeloid leukemia (AML). We investigated telomere length (TL), telomerase activity (TA) and hTERT, c-myc, mad1, and p53 expression in the bone marrow of patients with MDS (n = 109), AML (n = 47) and in controls (n = 24). TL was lower in MDS patients than in controls (p < 0.001) and higher in L-MDS (low, intermediate-1 IPSS, p < 0.01) respect H-MDS (high, intermediate-2 IPSS, p < 0.01) patients. Mad-1 expression was higher in MDS patients than in controls (p < 0.01), c-myc expression was highest in AML and in H-MDS patients. Our results show that the telomere dynamics might be useful for stratifying patients according to a risk scoring system.     

Myelodysplastic syndromes with deletions of chromosome 11q lack cryptic MLL rearrangement and exhibit characteristic clinicopathologic features

Deletions of chromosome 11q[del(11q)] as part of a non-complex karyotype are infrequent in myelodysplastic syndromes (MDS), leaving the clinicopathologic and genetic features largely undefined. From three large medical centers over a 10-year period, we identified 32 MDS cases where del(11q) was present either as a sole (n = 23) or associated with another abnormality (n = 9), showing an overall 0.6% frequency in MDS. These patients included 15 men and 17 women, with a median age of 68 years. Three were therapy-related, and 29 were primary MDS. These cases were characterized by transfusion-dependent anemia (65%); frequent ring sideroblasts (RS) (59%); bone marrow hypocellularity (22%), and less severe thrombocytopenia. With a median follow-up of 32 months, 9/24 (38%) cases progressed to acute myeloid leukemia (AML), and the overall survival (OS) was 35 months (3-105). Fluorescence in situ hybridization (FISH) showed MLL deletion in 6/10 cases, but no cryptic MLL translocations in all 15 MDS cases tested. In contrast, FISH performed in AML with del(11q) showed MLL rearrangement in 3/17 (18%) cases. In summary, del(11)q occurring in a non-complex karyotype is predominantly associated with primary MDS, lack of cryptic MLL rearrangements, and shows characteristic clinicopathological features. These clinicopathological features are likely attributed to commonly deleted regions of 11q and their involved genes.     

Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine

TP53 mutations are found in 5–10% of MDS and AML, where they are generally associated with complex karyotype and an overall poor prognosis. However, the impact of TP53 mutations in MDS treated with azacitidine (AZA) remains unclear. We analyzed TP53 mutations in 62 patients with high risk MDS or AML treated with AZA. A TP53 mutation was found in 23 patients (37.1%), associated with complex karyotype in 18 (78.3%) of them. TP53 mutations had no significant impact on response or complete response to AZA (p = 0.60 and p = 0.26, respectively). By univariate analysis, OS was negatively influenced by the presence of TP53 mutation (median OS 12.4 months versus 23.7 months, p < 10⁻⁴), abnormal cytogenetics (median OS 14.4 months vs 33 months, p = 0.02) complex cytogenetics (median OS 12.7 months versus 23.7 months, p = 0.0005), and a diagnosis of AML (median 14.5 months vs 21.2 months for MDS or CMML, p = 0.02). By multivariate analysis, only TP53 mutational status (HR 2.89 (95% confidence interval 1.38–6.04; p = 0.005) retained statistical significance for OS. Results were similar when the analysis was restricted to MDS and CMML patients, excluding AML (HR = 2.46 (95% confidence interval: 1.1–6.4); p = 0.04)).     

Lenalidomide and metronomic melphalan for CMML and higher risk MDS: A phase 2 clinical study with biomarkers of angiogenesis

Metronomic, low dose chemotherapy may have anti-angiogenic effects and augment the effects of lenalidomide in MDS and CMML. We evaluated the clinical efficacy, tolerability and anti-angiogenic effects of melphalan 2 mg and lenalidomide 10 mg for 21 days/28 in CMML (n = 12) and higher risk MDS (n = 8) patients in a prospective phase II study. The primary endpoint was overall response and secondary endpoints included survival, progression-free survival, toxicity and biomarkers of angiogenesis. The median age was 73 years, 55% were pretreated and transfusion dependent. The overall response rate was 3(15%) of 19 evaluable patients but 25% in CMML and 33% in pCMML. Dose reductions and/or delays were common due to myelosuppression. Transient spikes in circulating endothelial cells that declined below baseline were seen in responders and patients with CMML, suggesting anti-angiogenic activity. In conclusion, lenalidomide and metronomic low dose melphalan demonstrate signals of clinical and possible anti-angiogenic activity in patients with pCMML that require future validation. This trial was registered at clinicaltrial.gov under # NCT00744536.     

Characteristics and outcome of myelodysplastic syndromes (MDS) with isolated 20q deletion: a report on 62 cases

Isolated 20q deletion is common in MDS and considered of good prognosis, but no large series have been reported. We compared characteristics of 62 MDS patients with isolated del 20q, 36 patients with del 20q and other cytogenetic abnormalities, and 1335 MDS patients without del20q. Significant differences between MDS with isolated del 20q and patients without del 20q were lower platelet count (mean 144 vs. 196 G/l, p = 0.005), lower marrow blast count (mean 3.9% vs. 5.6%, p = 0.0008), and higher reticulocyte count (mean 72.5 vs. 51.7 G/l, p = 0.04). Ten (16%) patients with isolated del 20q had Hb > 12 g/dl and platelets <100 G/l, compared to 7.3% of patients without del 20q (p = 0.025). Review of marrow slides of those 10 patients showed that could be readily identified as MDS prior to cytogenetics. Fourteen percent of patients with isolated del 20q progressed to AML compared to 11% with one and 24% with several additional abnormalities. Median survival was 54 months in patients with isolated del 20q, not reached and 12 months for del 20q with one and several additional abnormalities, respectively (p = 0.035) confirming the favorable prognosis of del 20q without complex abnormalities.     

Epidermal growth factor receptor mutation analysis in previously unanalyzed histology samples and cytology samples from the phase III Iressa Pan-ASia Study (IPASS)

Objectives

Epidermal growth factor receptor (EGFR) mutation testing is standard practice after lung adenocarcinoma diagnosis, and provision of high-quality tumor tissue is ideal. However, there are knowledge gaps regarding the utility of cytology or low tumor content histology samples to establish EGFR mutation status, particularly with regard to the proportion of testing performed using these sample types, and the lack of an established link with efficacy of treatment.

Methods

The randomized phase III Iressa Pan-ASia Study (IPASS; ClinicalTrials.gov identifier NCT00322452) of first-line gefitinib versus chemotherapy analyzed samples meeting preplanned specifications (n = 437 evaluable for EGFR mutation; n = 261 mutation-positive). This supplementary analysis assessed tumor content and mutation status of histology (n = 99) and cytology samples (n = 116) which were previously unanalyzed due to sample quality, type, and tumor content (<100 cells). Objective response rate (ORR) and change in tumor size with gefitinib treatment were assessed.

Results

EGFR mutation testing was successful in 80% and 19% of previously unanalyzed histology and cytology samples, respectively. Mutations were detected in 54 tumors previously described as mutation-unknown (histology, n = 45; cytology, n = 9). ORRs in mutation-positive cytology (83%) and histology (74%) subgroups were consistent with previous analyses (71%). Tumor size decrease was consistent across previously analyzed and unanalyzed samples (all mutation subgroups), with less consistency across ORRs in mutation-negative cytology (16%) and histology (25%) subgroups versus the previous analysis (1%).

Conclusions

Histology samples with low tumor content and cytology samples can be used for EGFR mutation testing; patients whose mutation status was confirmed using these sample types achieved a response to treatment consistent with those confirmed using high-quality histology samples. Better sample quantity/quality can potentially reduce false-negative results.     

Diagnostic and prognostic value of alpha internexin expression in a series of 409 gliomas

The neuronal intermediate filament alpha internexin (INA) is expressed in most gliomas with 1p19q codeletion and could represent a valuable prognostic marker in clinical routine. INA expression was analysed on 409 gliomas and correlated with histology, progression free survival (PFS), overall survival (OS), genomic profile assessed by CGH-array, IDH1/IDH2 mutation and p53 expression. INA was expressed in 59% of grade II oligodendrogliomas (n = 73), 45% of grade III oligodendrogliomas (n = 133), 15% of grade II oligoastrocytomas (n = 61), 12% of grade III oligoastrocytomas (n = 41), 23% of glioblastomas with oligodendroglial component (n = 31), 0% of grade I astrocytomas (n = 3), 0% of grade II astrocytomas (n = 14), 6% of grade III astrocytomas (n = 17) and 0% of glioblastomas (n = 36). INA expression was detected in 85% of gliomas with complete 1p19q codeletion (‘true 1p19q signature’) (n = 85) versus 15% of gliomas without 1p19q codeletion (n = 245), including 14% of gliomas with variable/partial 1p19q deletion (‘false 1p19q signature’) (n = 72) (p < 0.0001). INA was expressed by 43% of gliomas with IDH1 mutation (n = 197) versus 12% of gliomas without IDH1 mutation (n = 156) (p < 0.0001). In oligodendroglial gliomas (n = 240), INA expression specificity for 1p19q codeletion was 80%, sensitivity 85%, positive predictive value 70%, and negative predictive value was 91%. Combining INA and p53 expressions improved INA predictive accuracy for 1p19q codeletion. In grade III gliomas, INA expression was associated with longer PFS (42.1 versus 10.2 months, p = 0.0007) and longer OS (124.6 versus 20.6 months, p = 0.0001). In conclusion, INA expression is a fast, cheap and reliable prognostic marker, and represents a surrogate marker for 1p19q complete codeletion.     

Pattern of hypomethylating agents use among elderly patients with myelodysplastic syndromes

Little is known about how hypomethylating agents (HMAs) have been adopted into the treatment of myelodysplastic syndromes (MDS). We conducted a population-based study to assess the use of HMAs among 4416 MDS patients (age ≥66 years) who were diagnosed during 2001-2005 and followed up through the end of 2007. Multivariate logistic regression models were utilized to evaluate the role of various patient characteristics. 475 (10.8%) patients had received HMAs by 2007, with the proportion increasing over time. Patients who were white (odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.46-0.95), male (OR = 1.47, 95% CI: 1.19-1.82), young (P_trend < 0.01), more recently diagnosed (OR = 1.90, 95% CI: 1.54-2.34), had fewer comorbidities (P_trend < 0.01), or had a history of other cancer (OR = 1.28, 95% CI: 1.00-1.63) were more likely to receive HMAs. Compared with patients with refractory anemia, those diagnosed with refractory anemia with excess blasts or refractory cytopenia with multilineage dysplasia had a higher chance to be treated with HMAs (OR = 3.52 and 2.32, respectively). Relatively few MDS patients were treated with HMAs during the introduction period of these agents, and multiple patient characteristics such as sex, comorbidities, and MDS subtype influence the likelihood a patient receives HMAs.     

Serum iron metabolism and erythropoiesis in patients with myelodysplastic syndrome not receiving RBC transfusions

Dysregulation of hepcidin, a key iron regulating hormone, is important in the pathogenesis of iron overload in patients with myelodysplatic syndrome (MDS). However, most studies of hepcidin levels are complicated by concomitant RBC transfusions. To evaluate the relationship between iron metabolism and erythropoiesis, we measured serum levels of hepcidin, growth-differentiation factor-15 (GDF15) and other markers of erythropoiesis in 107 subjects with MDS not receiving RBC transfusions. Patients with MDS had significantly higher levels of hepcidin than normals. However, their hepcidin–ferritin ratio was markedly decreased compared to normals (P < 0.001) and varied substantially between MDS subtypes (P = 0.011). GDF15 levels positively correlated with percent of bone marrow erythroblasts (P < 0.001), soluble transferrin receptor (sTfR) (P = 0.018), and also with transferrin saturation (ISAT) (P = 0.038). The hepcidin–ferritin ratio negatively correlated with serum erythropoietin (EPO) levels (P < 0.001), and also with GDF15 levels (P = 0.014). Colony forming cells (CFC) were evaluated in 70 subjects. Those with serum ferritin (SF) levels <500 ng/ml had significantly more BFU-E than subjects with SF ≥ 500 ng/L (P = 0.007), but numbers of granulocyte/macrophage-colony-forming cells (CFU-GM) were similar (P = 0.190). Our data indicate serum hepcidin levels are inappropriately low in patients MDS not receiving RBC transfusions. GDF15 levels correlated with low hepcidin levels and may contribute to iron overload in this setting. Iron overload may in turn suppress erythropoiesis by imparing the proliferative capacity of the erythroid progenitor cells.     

Young age and a positive family history of colorectal cancer are complementary selection criteria for the identification of Lynch syndrome

Families at high risk for Lynch syndrome can effectively be recognised by microsatellite instability (MSI) testing. The aim of the present study is to compare the effectiveness of a MSI test for the identification of Lynch syndrome in patients selected by a pathologist mainly based on young age at diagnosis (MSI-testing-indicated-by-a-Pathologist; MIPA), with that of patients selected by a clinical geneticist mainly based on family history (MSI-testing-indicated-by-Family-History; MIFH).Patients with a Lynch syndrome associated tumour were selected using MIPA (n = 362) or MIFH (n = 887). Germline DNA mutation testing was performed in 171 out of 215 patients (80%) with a MSI positive tumour.MSI was tested positive in 20% of the MIPA-group group compared to 16% in the MIFH-group (P = 0.291). In 91 of 171 patients with MSI positive tumours tested for germline mutations were identified as Lynch syndrome patients: 42% in the MIPA-group and 56% in the MIFH-group (P = 0.066). Colorectal cancer (CRC) or endometrial cancer (EC) presenting at an age below 50 years would have led to the diagnosis of Lynch syndrome in 89% of these families (CRC below 50 years: 88% and EC below 50 years: 12%). Families detected by MIPA were characterised more often by extracolonic Lynch syndrome associated malignancies, especially EC (P < 0.001).Our results indicate that recognition of Lynch syndrome by CRC or EC below 50 years is as effective as a positive family history. Families from patients selected by individual criteria more often harbour extracolonic Lynch syndrome associated malignancies.     

Detoxification and DNA repair genes polymorphisms and susceptibility of primary myelodysplastic syndromes in Chinese population

Molecular epidemiological studies have found new insights into the etiology of myelodysplastic syndromes (MDS). We analyzed the polymorphisms of 5 genes in 275 patients with primary MDS and 354 healthy controls in an attempt to identify candidate genetic risk factors for primary MDS in Chinese Han population. There was no difference in polymorphic variants of GSTM1, NQO1-C609T and XRCC3-C241T between the patients and controls. The homozygous variant C/C of RAD51-G135C was found to increase the susceptibility to MDS (OR, 4.13; p = 0.001) and the risk of MDS association with structural abnormal karyotype (OR, 7.67; p = 0.001). In addition, the null genotype of GSTT1 was correlated MDS patients with complex aberrant karyotype (OR, 3.25; p = 0.012). These potential genetic predisposition suggested their possible involvement in the multistep pathogenesis of MDS.     

The prevalence and burden of symptoms amongst cancer patients attending palliative care in two African countries

Background

The majority of cancer presentations in Africa are advanced and incurable, with incidence of malignancies projected to increase significantly. Despite the African cancer burden, almost nothing is known about the symptomatology of malignant progressive disease. This study aimed to determine the symptom prevalence and burden amongst advanced cancer patients in two African countries.

Methods

The Memorial Symptom Assessment Schedule Short Form (MSAS-SF) was used to measure the 7-d period prevalence and associated burden of multidimensional symptoms amongst adult patients attending palliative care in South Africa and Uganda. Further demographic and clinical variables were collected.

Results

Of the 112 patients recruited, 22 (19.6%) had an underlying HIV diagnosis. The most common cancer primaries were breast (N = 24), cervix (N = 21) and lung (N = 14). The mean number of symptoms was 18 (SD = 6.6). The five most prevalent symptoms were pain (87.5%), lack of energy (77.7%), feeling sad (75.9%), feeling drowsy (72.3%) and worrying (69.6%). The five symptoms ranked as most severe were as follows: pain n = 26 (23.2%), sexual problems n = 24 (21.4%), weight loss n = 21 (18.8%), ‘I don’t look like myself’ n = 21 (18.8%) and lack of energy n = 20 (17.9%).

Discussion

Pain and psychological problems were four of the five most common symptoms, found in more than 3 out of 4 patients. Our sample’s reported mean number of symptoms was far higher than reported in other global studies. These data can inform the delivery of appropriate clinical care. The prevalence of multidimensional symptoms underlines the importance of holistic approaches to patient assessment and management, taking account of multiple and potentially interacting symptoms and locally appropriate intervention.     

High levels of global DNA methylation are an independent adverse prognostic factor in a series of 90 patients with de novo myelodysplastic syndrome

The prognostic impact of global DNA methylation and hydroxymethylation was assessed in 90 patients with de novo myelodysplastic syndrome (MDS). DNA was isolated from bone marrow samples obtained at diagnosis and global methylation and hydroxymethylation were determined by ELISA. Patients with a percentage of methylated DNA above 2.73% had a shorter overall survival than those with lower levels (P = 0.018) and presented a negative trend in terms of leukemia-free survival (P = 0.084), that was statistically significant after censoring 9 patients that received disease-modifying treatments both in univariate and multivariate analyses. Similarly, the low-risk MDS patients defined by the IPSS, WPSS and IPSS-R with 5-mC percentage in total DNA above 2.73% had a shorter overall survival (P = 0.032; P = 0.023; P = 0.031). No cut-off value for the 5-hydroxymethylcytosine percentage with statistical significance for overall or leukemia-free survival was obtained. This study suggests that global DNA methylation predicts overall survival in myelodysplastic syndromes.     

Aberrant methylation of the RIZ1 gene in myelodysplastic syndrome and acute myeloid leukemia

We performed methylation specific PCR analysis on the RIZ1 promoter in MDS and AML. Methylation was detected in 17 of 34 MDS (50%) and 22 of 72 AML (31%) (p = 0.053). Methylation was detected in eleven of 17 secondary AML from MDS (65%), and eleven of 55 de novo AML (20%) (p = 0.0005). Bisulfite sequence revealed methylation at many CpG sites in the promoter. Decreased RIZ1 expression was accompanied by methylation in six of nine samples examined, while it was also observed in seven of 13 without methylation. Treatment of AML cells, that have RIZ1 methylation, with 5-Aza-dC, induced growth suppression with RIZ1 restoration. Our results suggest that the RIZ1 gene is inactivated in MDS and AML in part by methylation, whereas another mechanism should be involved in others.     

EGFR mutations and clinical outcomes of chemotherapy for advanced non-small cell lung cancer: A meta-analysis

Background

This meta-analysis was performed to assess whether epidermal growth factor receptor (EGFR) mutation status was associated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy.

Method

We systematically identified eligible articles investigating the effects of chemotherapy in patients with NSCLC stratified by EGFR mutation status. The summary risk ratio (RR) for ORR and hazard ratios (HRs) for both PFS and OS were calculated using the inverse variance formula of meta-analysis.

Results

Identification for the current meta-analysis: 5 prospective studies (n = 875) and 18 retrospective studies (n = 1934) for ORR; 2 prospective studies (n = 434) and 10 retrospective studies (n = 947) for PFS; 2 prospective studies (n = 438) and 7 retrospective studies (n = 711) for OS. The ORR was significantly higher in patients with EGFR mutations in prospective studies (RR = 1.42; 95% confidence interval [CI], 1.16–1.74; P = 0.001), but not in retrospective studies (RR = 1.12; 95% CI, 0.96–1.32; P = 0.146). There was no obvious association between EGFR mutations and PFS both in prospective (HR = 0.84; 95% CI: 0.65–1.09; P = 0.197) and retrospective (HR = 1.02; 95% CI: 0.87–1.18; P = 0.838) studies. Association between EGFR mutations and OS was also not seen in prospective studies (HR = 0.74; 95% CI: 0.27–2.05; P = 0.566), but was seen in retrospective studies (HR = 0.48; 95% CI: 0.33–0.72; P < 0.001; I² = 75.9%; P < 0.001) with significant heterogeneity.

Conclusion

EGFR mutations in advanced NSCLC may be associated with higher ORRs to chemotherapy, but may have nothing to do with PFS and OS. Further prospective studies are required to identify the influence of EGFR mutations on chemotherapy effects in advanced NSCLC.     

Herbal therapy use by cancer patients: a literature review on case reports

Complementary and alternative medicine use is common amongst cancer patients. In many surveys, herbal medicines are amongst the most commonly used group of treatments. Herbal remedies are believed by the general public to be safe, cause less side-effects and less likely to cause dependency.The authors performed a literature review to assess which herbal approaches have had associated cancer case reports and determine which of these have been studied in prospective research. Eighteen case reports of patients having apparent antitumour effects from herbal therapy and 21 case reports of toxic effects of herbs used by cancer patients were identified. Clinicaltrials.gov and MEDLINE (via PubMed) were searched for each of the herbal products identified in these reports. Clinical trials in cancer populations were identified for green tea extracts or compounds (n = 34), phytoestrogens (n = 27), mistletoe (n = 8), Ganoderma lucidum (n = 1), noni (n = 1) and Silymarin (n = 1). Daikenchuto, PC-SPES, Nyoshinsan/TJ and Saw palmetto have also been studied prospectively.In conclusion, some of the herbs with promising case report findings have undergone prospective clinical investigations but many others have either not yet been explored or the results have not been reported in English. Unconventional therapies, such as herbs and minerals, used in ancient medical traditions have led to the identification of active anticancer agents. Mechanisms to support prospective research with such approaches are discussed.     

CXXC4 mRNA levels are associated with clinicopathological parameters and survival of myelodysplastic syndrome patients

Objective

The CXXC domain protein 4 (CXXC4) functions as a negative regulator of Wnt signaling and also regulates expression of the ten-eleven translocation 2 (TET2) protein for DNA methylation. This study detected levels of CXXC4 and TET2 mRNA to determine their association with survival of patients with myelodysplastic syndrome (MDS).

Methods

Levels of TET2 and CXXC4 mRNA were analyzed in bone marrow samples from 154 MDS patients and 50 control subjects using qRT-PCR and subsequently associated these levels with clinicopathological characteristics and survival of MDS patients.

Results

Levels of TET2 and CXXC4 mRNA were significantly lower in MDS patients than that in controls (P = 0.009 and P < 0.001, respectively). Patients with advanced WHO subtypes (e.g., RAEB-1 and RAEB-2) exhibited a higher level of CXXC4 mRNA (P = 0.020) compared to those with early stage subtypes (i.e., RA, RARS, RCMD, RCMD-RS, 5q-syndrome, and MDS-U). Moreover, levels of CXXC4 mRNA were associated with marrow blast levels (P = 0.014) and neutrophil counts (P = 0.039). Levels of CXXC4 mRNA and hemoglobin and IPSS cytopenias were associated with the overall survival (P = 0.025) but not with the leukemia-free survival of MDS patients. The multivariate analysis demonstrated that the age of patients and levels of hemoglobin and marrow blast were independent risk factors for survival of MDS patients.

Conclusion

This study demonstrated that the age of patients and levels of CXXC4 mRNA, hemoglobin, and marrow blast associated with survival of MDS patients.     

Genomic aberrations deletion 11q and deletion 17p independently predict for worse progression-free and overall survival after allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia

Chronic lymphocytic leukemia remains incurable despite availability of potent chemoimmunotherapy regimens. Allogeneic hematopoietic cell transplantation (HCT) is the only modality that offers the possibility of cure. To identify predictors of progression-free and overall survival, we evaluated outcomes of 43 consecutive patients who received an allograft for advanced CLL. The majority received a reduced intensity conditioning regimen (n = 37). Donors were HLA matched-related (n = 18), matched-unrelated (n = 15), mismatched-unrelated (n = 7), or umbilical cord blood (n = 3). The median progression-free (PFS) and overall survival (OS) were 31.4 months and 46.4 months respectively. Twenty (46.5%) patients were alive and in complete remission at a median follow-up of 31.4 months. NRM was higher than previously published series for CLL, likely due to a high burden of comorbidity (22 patients with HCT-CI ≥ 2) and a high proportion receiving HLA mismatched-unrelated donor or umbilical cord blood cells. Presence of del (11q), del(17p), or progressive disease at HCT are independent predictors of worse PFS and OS. New strategies are needed to improve survival outcomes in CLL associated with poor risk cytogenetics.