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7001 Background: The inability to receive L-asparaginase (ASNase) therapy due to hypersensitivity is associated with inferior outcomes in patients with ALL or LBL. JZP458, a recombinant Erwinia-derived ASNase from a Pseudomonas fluorescens expression platform, is approved by the FDA for patients with ALL/LBL who have developed hypersensitivity to E. coli–derived ASNase. Here, we report the efficacy and safety of IM JZP458 from COG AALL1931, a phase 2/3, open-label, multicenter, pharmacokinetic (PK) study. Methods: Eligible patients with ALL/LBL had a grade ≥3 allergic reaction or silent inactivation to a pegylated E. coli–derived ASNase. Each remaining dose of pegylated E. coli–derived ASNase was replaced with 6 doses of IM JZP458 on Monday/Wednesday/Friday (M/W/F) over 2-weeks. Three dosing cohorts were enrolled: Cohort 1a, 25 mg/m2 M/W/F; Cohort 1b, 37.5 mg/m2 M/W/F; Cohort 1c, 25 mg/m2 M/W and 50 mg/m2 F. Efficacy was assessed by the proportion of patients who achieved the last 72-hour (primary endpoint) or 48-hour (key secondary endpoint) nadir serum asparaginase activity (NSAA) levels ≥0.1 IU/mL in the first treatment course. A population PK (PPK) model was developed based on SAA data from AALL1931 to characterize the PK of JZP458 and to inform dosing decisions. Results: 167 patients were enrolled for IM dosing (Cohort 1a, n = 33; Cohort 1b, n = 83; Cohort 1c, n = 51). The median (range) age was 10 (1, 25) years. The median (range) of JZP458 courses received was 5 (1, 14) for Cohort 1a, 5 (1, 15) for Cohort 1b, and 4 (1, 11) for Cohort 1c. Mean (95% CI) SAA levels (IU/mL) at 72-hour were 0.16 (0.12, 0.19) for Cohort 1a, 0.33 (0.27, 0.39) for Cohort 1b, and 0.47 (0.35, 0.59) for Cohort 1c; and 0.45 (0.37, 0.53), 0.88 (0.76, 1.01), and 0.66 (0.54, 0.77), respectively, at 48-hour. Simulated data from the PPK model matched the observed data well. For Cohort 1c, the proportions of patients (95% CI) achieving NSAA levels ≥0.1 IU/mL at the last 72- and 48-hour in Course 1 were 90% (81%, 98%) and 96% (90%, 100%), respectively, based on observed data; and were 92% (91%, 93%) and 94% (93%, 95%) based on modeled data. The Table shows the rates of treatment-related adverse events (TRAEs; all grades) of interest per cohort. Overall, TRAEs leading to discontinuation included pancreatitis (6%), drug hypersensitivity (4%), anaphylactic reaction (2%), increased alanine aminotransferase (1%), and hyperammonemia (1%). There were no TRAEs leading to death. Conclusions: The totality of the results from AALL1931 demonstrate the positive benefit-risk profile of the IM JZP458 dosing regimen of 25 mg/m2 M/W and 50 mg/m2 F with a safety profile consistent with other asparaginases. Clinical trial information: NCT04145531. [Table: see text]

Background: In patients with ALL, inability to receive L-asparaginase therapy due to hypersensitivity is associated with higher relapse risk (Gupta S, et al. J Clin Oncol. 2020). JZP458 is a recombinant Erwinia asparaginase derived from a novel Pseudomonas fluorescens expression platform to produce a reliable supply of enzyme with minimal immunologic cross-reactivity to E. coli-derived asparaginases. It has an amino acid sequence identical to that of native Erwinia asparaginase and its activity on asparagine is comparable based on in vitro measurements. This report includes initial analyses from the phase 2/3 open-label, multicenter, confirmatory pharmacokinetic (PK) and safety study (NCT04145531) of JZP458 in patients with ALL/LBL who developed hypersensitivity or silent inactivation to a long-acting E. coli-derived asparaginase. Methods: For eligible patients, each remaining course of long-acting E. coli-derived asparaginase was substituted by six doses of intramuscular (IM) JZP458 on a Monday/Wednesday/Friday (M/W/F) schedule. The primary efficacy endpoint of the trial was evaluated by the proportion of patients with the last 72-hr (primary endpoint) and last 48-hr (key secondary endpoint) nadir serum asparaginase activity (NSAA) level ≥0.1 IU/mL during the first treatment course. Cohort 1a started with 25 mg/m 2 IM JZP458 (M/W/F) and Cohort 1b explored a higher dose of 37.5 mg/m 2 IM M/W/F. A preliminary population pharmacokinetic (PPK) model using Cohort 1a and 1b data predicted that a regimen of 25 mg/m 2 (M/W) and 50 mg/m 2 (F) would be optimal to support M/W/F dosing and Cohort 1c was initiated using this regimen. Results: This initial report (data cutoff of Jan 11, 2021) provides data from 102 study patients enrolled in Cohort 1a (n=33, 51.5% male), 1b (n=53, out of 87 patients enrolled, 62.3% male), and 1c (n=16, out of 52 patients enrolled, 50.0 % male). The median (range) number of courses received in Cohorts 1a, 1b, and 1c as of the data cutoff was 4 (1, 14), 3 (1, 12), and 1 (1, 2), respectively, and 53% of patients were ongoing in treatment. The mean serum asparaginase activity (SAA) levels (95% confidence intervals [CIs]) for evaluable patients in Cohorts 1a, 1b, and 1c at 48 hrs were 0.4489 IU/mL (0.3720, 0.5258), 0.8376 IU/mL (0.6813, 0.9939), and 0.5085 IU/mL (0.3261, 0.6908); and at 72 hrs were 0.1543 IU/mL (0.1162, 0.1924), 0.3000IU/mL (0.2269, 0.3730), and 0.3579 IU/mL (0.2184, 0.4974). The proportion of patients achieving NSAA ≥0.1 IU/mL at 48 and 72 hr time points are presented in Table 1. PPK modeling and simulation analysis suggested that JZP458 given IM as 25 mg/m 2 on M/W and 50 mg/m 2 on F was expected to achieve NSAA levels ≥0.1 IU/mL in 99.8% of patients (95% CI: 99.6%, 100%) at 48 hours and 97.3% of patients (95% CI: 96.5%, 98.0%) at 72 hours. Grade 3 or higher treatment-emergent adverse events, regardless of causality, occurred in 73/102 (72%) patients. Adverse drug reactions (ADRs) are shown in Table 2. These ADRs are consistent with the safety profile observed with other asparaginases. Conclusions: The JZP458 IM dosing regimen of 25 mg/m 2 M and W, and 50 mg/m 2 F demonstrates a positive benefit:risk profile, achieving SAA levels ≥0.1 IU/mL in >90% of patients studied at both 48- and 72-hrs and a safety profile that is consistent with what has been observed in published literature on asparaginases. Figure 1 Figure 1. Disclosures Maese: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Loh: MediSix therapeutics: Membership on an entity's Board of Directors or advisory committees. Lin: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Aoki: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Zanette: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Agarwal: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Silverman: Jazz Pharmaceuticals: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Choi: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Silverman: Takeda, Servier, Syndax, Jazz Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Raetz: Pfizer: Research Funding; Celgene: Other: DSMB member. Rau: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Servier Pharmaceuticals: Consultancy; AbbVie Pharmaceuticals: Other: Spouse is employee and stock holder.

Background T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive disease. In this study, we report our experience from 119 patients with T-PLL. Patients and methods We reviewed the clinico-pathologic records of 119 consecutive patients with T-PLL, who presented to our institution between 1990 and 2016. Results One hundred and nineteen patients with T-PLL were analysed. Complex karyotype and aberrations in chromosome 14 were seen in 65% and 52% patients, respectively. Seventy-five patients (63%) were previously untreated and 43 (37%) were initially treated outside our institution. Sixty-three previously untreated patients (84%) received frontline therapies. Overall, 95 patients (80%) have died. Median overall survival (OS) from diagnosis was 19 months [95% confidence interval (CI) 16-26 months]. Using recursive partitioning (RP), we found that patients with hemoglobin

The prognosis of patients with leukemia largely depends on the type of leukemia, clinical and pathologic prognostic factors of the leukemic cells, and patient characteristics. Over the past decade, long-term survival rates of patients with chronic myeloid leukemia (CML) have dramatically improved. On the other hand, these patients usually require life-long treatment, which may cause chronic physical, psychological, or socioeconomic complications that can affect patients’ well-being. Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the United States. The natural history of CLL is generally indolent, with median survival durations of 10 years. Patients with CLL are at risk for secondary malignancies and infectious complications with disease- and treatment-related pathogenesis. Patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are generally treated with intensive chemotherapy, which may result in chronic symptoms that interfere with patients’ daily lives. Although some aspects of late or chronic toxic effects of treatment in patients with leukemia have been discussed, data concerning long-term effects remain limited. Further investigation is warranted to establish optimal monitoring schedules and effective interventions for survivors of adult-onset leukemia.

The human androgen-receptor gene (HUMARA) has been used for analysis of X chromosome inactivation (XCI) pattern because of a polymorphic short tandem repeat (STR) near the 5'-promoter region correlated with XCI. We introduce a novel method to analyze XCI pattern, named HUMARA methylation-specific PCR (HUMARA-MSP) assay, which analyzes methylation status of the HUMARA gene by bisulfite modification instead of a methylation-sensitive restriction enzyme. Although the original MSP method shows whether there is a methylated band or not, our HUMARA-MSP method identifies the patterns of methylated and unmethylated bands. Because this method identifies either unmethylated or methylated alleles in each PCR tube and shows opposite band patterns dependent on methylation status, we can assess the XCI pattern independently twice. This method can avoid false results by incomplete enzyme digestion and incomplete bisulfite modification will not affect the results. Extremely small quantities of samples, such as hematopoietic colonies, were also available for HUMARA-MSP assay. Because DNA modified by sodium bisulfite is also available for assessment of methylation status of other genes by setting specific primers for them, we performed the simultaneous assessment of clonality and aberrant hypermethylation of p15INK4B gene in myelodysplastic syndromes. These simultaneous assessments were easily possible and provided much information despite requiring only a small volume of DNA. The HUMARA-MSP assay may facilitate the analyses for pathogenesis of hematological disorders because of its simplicity, sensitivity and wide applicability. Leukemia (2000) 14, 207-212.

Background: T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive mature T-cell lymphoid leukemia. T-PLL is diagnosed based on characteristic immunophenotype, cytogenetic, and molecular aberrations (including members of the JAK-STAT signaling pathway) which may explain its aggressive clinical course. Cytogenetic features include chromosome (chr) 14 aberrations, accompanied by gene rearrangement involving proto-oncogenes TCL1 or MTCP1. In this analysis, we report our single-institution experience with T-PLL over the last 25 years. Methods: We reviewed the clinico-pathologic records of 101 consecutive patients (pts) with T-PLL, who presented to our institution between 1990 and 2015. The survival (OS) of pts was calculated from the date of initial presentation to the date of last follow up. Kaplan-Meier product limit method was used to estimate the median OS. Results: Median age of pts was 64 years (range 35-87 years). Eighteen pts (18%) presented with a performance status of 2 or higher. Lymphadenopathy, splenomegaly, skin lesions, hepatomegaly and pleural effusion were seen in 58%, 37%, 30%, 8%, and 7% of pts, respectively. Complex karyotype and aberrations in chr 14 were seen in 54 (63%) and 42 (49%) pts, respectively. TCL1 expression by immunohistochemistry was performed in 29 pts. The overexpression of TCL1 was detected in 23/29 pts (79%). Among untreated pts, 18/47 (38%) had a chr abnormality involving TCL-1. At initial presentation to our center, 59 pts (58%) were untreated and 42 pts (42%) had relapsed/refractory disease with a median of 2 prior treatments (range 1-6). Seventy-one pts (70%) were treated at our institution. Median overall OS from diagnosis in all pts was 21.7 mos (Range 1.5-107.7 mos). Median OS was longer in untreated pts than in pts with relapsed/refractory disease (27 mos vs. 17 mos; P=0.08). In a multivariate analysis for assessing the prognostic factors for OS in 43 untreated pts in whom all variables were available, we found that the presence of a pleural effusion HR (95% CI) 5.21 (1-27; P Conclusions: In this retrospective analysis, we have observed that outcomes in T-PLL remain poor. We have shown that alemtuzumab has some therapeutic activity in pts with T-PLL but durable remissions are uncommon. Rarity of this disease limits the conduct of large scale clinical trials; hence multicenter collaborative effort is required to conduct prospective studies. In pts who achieve a CR, consolidation treatment with SCT did not improve survival in our series. Studies to further define the genomic imbalances in pts with T-PLL and identify potential therapeutic targets and pathways providing drug resistance in T-PLL are underway. Table 1 Summary of treatment response and outcomes according to the type of therapy *Censored at stem cell transplant. Table 1. Summary of treatment response and outcomes according to the type of therapy. / *Censored at stem cell transplant. Figure (A-B) - Survival of pts after treatment with frontline therapy A) with/without stem cell transplantation after initial remission. B) With/without TCL-1 rearrangements. Figure. (A-B) - Survival of pts after treatment with frontline therapy A) with/without stem cell transplantation after initial remission. B) With/without TCL-1 rearrangements. Disclosures O'Brien: Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria. Wierda:Acerta: Research Funding; Novartis: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Genentech: Research Funding. Jain:Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Novimmune: Consultancy, Honoraria; Abbvie: Research Funding; Servier: Consultancy, Honoraria; Seattle Genetics: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Infinity: Research Funding; Incyte: Research Funding; BMS: Research Funding. Thompson:Pharmacyclics: Consultancy, Honoraria. Kantarjian:BMS, Pfizer, Amgen, Novartis: Research Funding.

Purpose of the review Epigenetic changes marked by DNA methylation are known to contribute to the malignant transformation of cells by silencing critical genes. Decitabine inhibits DNA methyltransferase and has shown therapeutic effects in patients with hematologic malignancies. However, the connection between the clinical activity of decitabine and its demethylating activity is not clear. Herein, we summarize the results of recent clinical trials of decitabine in hematologic malignancies, and review the translational research into decitabine's mechanism of clinical activity. Recent findings Low-dose decitabine has been studied recently in multiple clinical trials and has been shown to be effective for treatment of myelodysplastic syndromes. Correlative laboratory studies of clinical trials have shown that decitabine induces global hypomethylation as well as hypomethylation of gene-specific promoters and activation of gene expression. Past a given threshold, induction of higher degrees of hypomethylation is not directly associated with a better clinical outcome. Moreover, studies have suggested that patients with promoter hypermethylation of p15 INK4B at baseline have paradoxically a lower chance of achieving response than those without hypermethylation. Furthermore, several other genes activated by decitabine were independent of hypomethylation in the promoter regions. Conclusion While at least part of decitabine's activity is through induction of hypomethylation and reactivation of critical genes, mechanisms independent from hypomethylation are also important for decitabine's antitumor activity.

Although sugar has been suggested to promote floral transition in many plant species, growth on high concentrations (5% [w/v]) of sucrose (Suc) significantly delayed flowering time, causing an increase in the number of leaves at the time of flowering in Arabidopsis. The effect of high concentrations of Suc seemed to be metabolic rather than osmotic. The delay of floral transition was due to extension of the late vegetative phase, which resulted in a delayed activation of LFY expression. In addition, growth on low concentrations (1% [w/v]) of Suc slightly inhibited flowering in wild-type plants. This delay resulted from effects on the early vegetative phase. This inhibition was more pronounced intfl1, an early flowering mutant, than in the wild type. Although 1% (w/v) Suc was reported to promote floral transition of late-flowering mutants such as co,fca, and gi, floral transition in these mutants was delayed by a further increase in Suc concentration. These results suggest that sugar may affect floral transition by activating or inhibiting genes that act to control floral transition, depending on the concentration of sugars, the genetic background of the plants, and when the sugar is introduced. Growth on 1% (w/v) Suc did not restore the reduced expression levels of FT andSOC1/AGL20 in co or fcamutants. Rather, expression of FT andSOC1/AGL20 was repressed by 1% (w/v) Suc in wild-type background. The possible effects of sugar on gene expression to promote floral transition are discussed.

We previously reported that the hypermethylation of the p15INK4B gene promoter was frequently observed in myelodysplastic syndromes (MDS), and that it may be associated with disease progression. An unanswered question is whether p15INK4B gene methylation is restricted to undifferentiated blastic cells, or whether differentiated cells such as granulocytes or erythrocytes of MDS origin also harbor this epigenetic alteration. In this study, we analyzed the methylation status of the p15INK4B gene in MDS by the methylation-specific PCR (MSP) method, which is more sensitive than Southern blotting. The bone marrow mononuclear cells (BM-MNCs) of 23 MDS patients were analyzed, and six of them showed p15INK4B methylation. Progenitor assay with methylcellulose medium was also performed in all patients. In two of the six patients with p15INK4B-methylated BM-MNCs, erythroid and/or non-erythroid colonies formed were subjected to molecular analysis. Colonies with and without p15INK4B methylation were detected in both patients. Furthermore, X-chromosome inactivation (XCI) pattern of each colony was simultaneously determined by MSP-based human androgen receptor gene analysis (HUMARA-MSP), and all p15INK4B-methylated colonies showed the same XCI pattern, which was dominant among the colonies, while p15INK4B-unmethylated colonies showed both patterns of XCI, in each of the two patients. We then examined the methylation status of the p15INK4B gene of granulocyte (PB-PMN) fractions from 10 patients with available peripheral blood cells. In all four patients with p15INK4B-methylated BM-MNCs, their PB-PMNs showed p15INK4B methylation. These results suggest that p15INK4B methylation in hematopoietic cells in MDS patients is restricted to the MDS clone but not necessarily to blast cells.

Expression levels of DNA methyltransferase genes do not correlate with p15 INK4B gene methylation in myelodysplastic syndromes

Abstract 4457 Chronic myeloid leukemia (CML) is effectively treated with imatinib (IM), however, several mathematical models and ex vivo-examinations suggested that IM-therapy does not eradicate BCR-ABL-positive hematopoietic stem cells (HSC). We prospectively (0, 3, 6 and 12 months after IM-therapy) investigated 16 newly diagnosed and 22 long-term followed CML-chronic phase (CP) cases using methods previously reported (Jamieson et al., N Engl J Med, 2004. and Abe et al., Int J Hematol, 2008) (Figure 1) with FACSAria™ and quantitative RT-PCR of BCR-ABL among each sorted population; total mononuclear cells, HSC/Thy-1+, HSC/Thy-1–, common myeloid progenitors (CMP), granulocyte macrophage progenitors (GMP) and megakaryocyte erythroid progenitors (MEP). In optimal responders to IM-therapy, BCR-ABL transcripts in the HSC populations (HSC/Thy-1+ and HSC/Thy-1–) tended to be more retentive than other populations while gradual reduction was observed during the first 12 months in all populations. And discrepancy of minimum residual diseases (MRD) between the HSC populations and other populations was larger in patients after longer IM-therapy. In evaluating properties of CML stem cells and other markers, we observed irrelevant distribution of side population (SP) and expressions of ABC transporters (ABCB1 and ABCG2) in comparison with CD34/38 expression. We also prospectively investigated BCR-ABL transcripts in each population of 23 IM-resistant or -intolerant CML-CP cases and one newly diagnosed CML-accelerated phase (AP) case during treatment with second-generation tyrosine kinase inhibitors (2nd TKIs), dasatinib or nilotinib. Treatment with each inhibitor induced more rapid reduction of BCR-ABL transcripts even in the HSC population (CD34+CD38–) during the first 6 months and there was no significant difference of MRD among each population in optimal responders to 2nd TKIs-therapy. In the stromal co-culturing system using primary cells and leukemic NOD/SCID/IL2rgnull (NOG) mice xenotransplanted with Ph+ leukemia cells, retention of quiescent slow-cycling (Hoechst 33342low/Pyronin Ylow) CD34+ population after IM-treatment were observed and cell death mechanisms after treatment with 2nd TKIs are also under investigation. These results imply that therapy with 2nd TKIs could be a promising approach for quick and efficient reduction of the CML stem cells and cure of disease. Figure 1 Figure 1. Disclosures: Naoe: Kyowa-Kirin: Research Funding; Novartis: Research Funding; Bristol-Myers Squibb: Research Funding.

6535 Background: The standard dose (SD) of imatinib for CP CML is currently 400 mg daily, but higher doses (HD) may be more effective. We conducted 2 consecutive trials using HD imatinib (i.e., 400mg twice daily) in previously untreated early CP CML pts. This is an updated analysis of the longer follow-up. Methods: A total of 175 previously untreated pts received HD imatinib. We compared the results with a previous study using SD imatinib (400mg/day) in untreated pts with early CP CML (N=50). Results: Cytogenetic and molecular responses were evaluable in 222 pts (N=49 at SD, 173 at HD) and 217 pts (N=46 at SD, 171 at HD), respectively. In HD group, Sokal risk classification was good in 69%, intermediate in 29%, and poor in 11% of pts. There were no differences in pre-treatment characteristics between two groups. The median age was 48 years in both groups. Median follow-up is 53 months for SD and 30 months for HD group. Patients treated with HD had a higher rate of complete cytogenetic responses (90% vs 78% with SD, p=0.03) and these occurred earlier, with 69% achieving this response after 6 months of therapy vs 45% with SD (p=0.001). The cumulative incidence of major molecular response was significantly better in HD group (p=0.03), and this response was also observed earlier in HD group: at 12 months 54% in HD and 24% in SD group had achieved this response (p=0.001). At 24 months, 19/70 (27%) evaluable pts with HD versus 3/31 (10%) of pts in SD group achieved complete molecular remission. Four pts (2%) in HD group and 4 pts (8%) in SD group have progressed to advanced phases (p=0.05). There was a trend in favor of the HD group for transformation-free-survival but it was not statistically significant (p=0.07). Overall survival is excellent in both groups (24 month survival, 99% with HD vs 98% with SD; p=0.24). Grade 3 or 4 hematologic toxicity was more frequent in HD group whereas extramedullary toxicity was similar in two groups. The median actual dose in HD group was 800 mg at 12 months, with 39% patients requiring dose reduction at some point. Conclusions: High-dose imatinib provides higher rates of complete cytogenetic responses and earlier molecular responses with some increase myelosupression. The long-term benefit of earlier responses remains to be demonstrated. [Table: see text]

Imatinib has remarkable activity in CML in all phases, with high rates of hematologic and cytogenetic response. However, in AP and BP responses are frequently less than complete hematologic remission (CHR), including partial hematologic remission (PHR) and return to chronic phase (second CP). The objective of this study was to investigate whether different responses to imatinib conferred a survival advantage in pts with CML in AP and BP. We evaluated 214 pts in AP and 76 pts in BP (11 lymphoid, 63 myeloid, 2 unclassified) treated with imatinib. Median age for AP pts was 49 yrs (range: 22–82 yrs) and for BP, 54 yrs (19–75 yrs). With a median follow-up of 49 months (1.9–67.5 months), 82 (38%) AP and 66 (87%) BP pts have died. A CHR and major cytogenetic (CG) response (MCR) have been achieved in 87% and 53% of AP pts, and 37% and 14% of BP pts, respectively. For AP pts the median overall survival (OS) and progression free survival (PFS) were 65 and 49 months, respectively. In BP pts, median OS and PFS were 7 and 3 months. The OS by best response to imatinib was as follows: Response No. (%) Median OS (months) p value Median PFS (months) p value CG CR=complete CG response (Ph=0%), CG PR=partial CG response (Ph We conclude that although cytogenetic responses confer the most survival advantage in AP and BP after imatinib therapy, hematologic responses are associated with a survival benefit.