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Background: The outcome of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone plus ofatumumab hyper-CVAD + ofatumumab (hyper-CVAD + ofatumumab) has not been compared with the outcome of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone plus ofatumumab hyper-CVAD plus rituximab (hyper-CVAD + Rituximab) in Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) in a randomized clinical trial.Methods: The authors compared the outcomes of 69 patients treated with hyper-CVAD + ofatumumab and 95 historical-control patients treated with hyper-CVAD + Rituximab. Historical-control patients were treated with hyper-CVAD + Rituximab if they had CD20 expression ≥ 20%. Ofatumumab (day 1 of course 1, 300 mg intravenously; subsequent doses, 2000 mg intravenously) was administered on days 1 and 11 of courses 1 and 3 and on days 1 and 8 of courses 2 and 4 for a total of 8 doses. A propensity score analysis with inverse probability of treatment weighting (IPTW) was performed to adjust for baseline covariates between groups.Results: The median event-free survival with stem cell transplantation (SCT) censoring was 33 and 65 months with hyper-CVAD + Rituximab and hyper-CVAD + ofatumumab, respectively (crude P = .064; IPTW P = .054). The median overall survival with SCT censoring was 52 months and not reached, respectively (crude P = .087; IPTW P = .097).Conclusions: Hyper-CVAD + ofatumumab was associated with better outcomes than hyper-CVAD + Rituximab among patients with newly diagnosed Philadelphia chromosome-negative ALL. [ABSTRACT FROM AUTHOR]

Background: Patients with relapsed/refractory (R/R) Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) have a poor prognosis and limited treatment options. Methods: The efficacy of inotuzumab ozogamicin (InO), a humanized anti‐CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, was evaluated in R/R ALL patients in the phase 1/2 study 1010 (NCT01363297) and open‐label, randomized, phase 3 study 1022 (INO‐VATE; NCT01564784). This analysis focused specifically on Ph+ R/R ALL patients. In study 1022, Ph+ patients were randomly assigned 1:1 to InO (n = 22) or standard intensive chemotherapy (SC) (n = 27) and 16 Ph+ patients in study 1010 received InO. Results: In study 1022, rates of complete remission/complete remission with incomplete hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity (patients achieving CR/CRi) were higher with InO (CR/CRi = 73%; MRD = 81%) versus SC (CR/CRi = 56%; MRD = 33%). The corresponding rates in study 1010 were 56% (CR/CRi) and 100% (MRD). The hematopoietic stem cell transplantation (HSCT) rate in study 1022 was 41% versus 19% for InO versus SC; however, there was no benefit in overall survival (median OS: 8.7 vs 8.4 months; hazard ratio, 1.17 [95% CI, 0.64‐2.14]). The probability of being event‐free (progression‐free survival) at 12 months was greater with InO versus SC (20.1% vs 4.8%). Conclusion: Given the substantial improvement in responses and rates of HSCT, InO is an important treatment option for patients with R/R Ph+ ALL. Future studies need to consider better characterization of disease characteristics, more sensitive MRD measurements, MRD‐directed therapy before HSCT, and potentially combination therapies, including tyrosine kinase inhibitors. An analysis of 65 patients with relapsed/refractory Philadelphia chromosome‐positive acute lymphoblastic leukemia shows that patients receiving inotuzumab ozogamicin (InO) have higher rates of complete remission/complete remission with incomplete hematologic recovery, minimal residual disease negativity, and subsequent hematopoietic stem cell transplantation than those receiving standard intensive chemotherapy (SC). Although this does not result in prolonged progression‐free survival or overall survival compared with SC, InO remains an important treatment option for patients with resistant and difficult‐to–treat disease. [ABSTRACT FROM AUTHOR]

Background: Dasatinib is a second-generation tyrosine kinase inhibitor that, when used as frontline therapy, produces more and faster cytogenetic and molecular responses compared with imatinib. The authors report the long-term follow-up from the first study using dasatinib as initial therapy for chronic-phase chronic myeloid leukemia.Methods: Between November 2005 and August 2014, patients were randomly assigned to receive 100 mg daily or 50 mg twice daily. After June 2009, all patients started with 100 mg daily.Results: With a median follow-up of 6.5 years, 94 of 149 treated patients (63%) were still receiving dasatinib on study. The median patient age was 48 years (interquartile range, 37-55 years), and 9% of patients had a high risk Sokal risk score. The cumulative complete cytogenetic response rate at 11 years was 92.6%, the major molecular response (MR) rate was 88.2%, and the MR4.5 rate (indicating a ≥4.5-log reduction in BCR-ABL1 transcripts) was 79.5%. The median time to a major MR and MR4.5 was 6 and 23 months, respectively. A sustained MR4.5 (≥2 years) was achieved in 82 patients (55%). The 10-year overall survival, transformation-free survival, event-free survival, and failure-free survival rates were 89%, 95%, 86%, and 65%, respectively. Univariate analysis showed that the achievement of a complete MR was associated with improved overall survival. The most common reasons for treatment discontinuation were toxicity and elective discontinuation. The most common treatment-emergent grade 3 and 4 adverse events were fatigue, thrombocytopenia, and infections.Conclusions: After this long-term follow-up, dasatinib continues to show an excellent safety profile and produces rapid cytogenetic responses and MRs, durable deep MRs, and excellent long-term survival outcomes in patients with chronic-phase chronic myeloid leukemia. [ABSTRACT FROM AUTHOR]

Background: Nilotinib is a potent, second-generation inhibitor of BCR-ABL1 tyrosine kinase and has been approved as frontline and salvage therapy for patients with chronic-phase chronic myeloid leukemia (CP-CML).Methods: In this single-institution, phase 2 study, 122 patients with newly diagnosed CP-CML received nilotinib 400 mg twice daily. The median follow-up on study was 78.3 months (interquartile range, 58.4-96.5 months).Results: Fifty-six percent of patients remained on therapy at the last follow-up. Both the complete cytogenetic response rate and the major molecular response (MR) rate were 91%. Seventy-five percent and 59% of patients achieved a ≥4.5-log reduction in BCR-ABL1 transcripts (MR4.5) and a sustained MR4.5 beyond 2 years, respectively. The estimated event-free survival and overall survival rates at 5 years were 89% and 93%, respectively, and the corresponding rates at 10 years were 85% and 88%, respectively. Treatment discontinuation due to toxicity occurred in 19% of patients, mostly because of cardiovascular events (10%) and biochemical abnormalities (6%). The top 3 nonhematologic toxicities were rash (55%), elevated bilirubin (57%), and elevated aminotransferases (48%). Hematologic toxicity was transient and mild. Ischemic cardiovascular adverse events occurred in 8% of patients. Four patients (3%) progressed to accelerated or blast phase while on therapy, and 7 patients (6%) died on study.Conclusions: The current data confirm the long-term efficacy of nilotinib 400 mg twice daily in patients with CP-CML. A majority of patients can achieve sustained MR4.5. [ABSTRACT FROM AUTHOR]

Background: Inotuzumab ozogamicin (InO) has demonstrated efficacy and tolerability in patients aged 18 to 78 years with relapsed/refractory acute lymphoblastic leukemia (ALL) in the INO-VATE trial. This subset analysis compared the efficacy and safety of InO in younger and older patients.Methods: Intent-to-treat analyses of morphologic responses and overall survival (OS) included 326 randomized patients, and safety assessments included 307 patients receiving 1 or more doses of the study treatment. Of the 326 patients, 164 received InO at a starting dose of 1.8 mg/m2 /cycle (0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15 of a 21- to 28-day cycle [≤6 cycles]); 60 patients were aged ≥55 years, and 104 were aged <55 years.Results: For older and younger patients, the median duration of InO therapy and the types and frequencies of adverse events of any grade were generally similar. Although the remission rates, median duration of remission (DOR), and progression-free survival were similar with InO for those aged <55 years and those aged ≥55 years, OS was longer for younger patients (median, 8.6 vs 5.6 months; hazard ratio, 0.610). Among patients proceeding to hematopoietic stem cell transplantation after InO treatment (28% of older patients and 58% of younger patients), the incidence of veno-occlusive disease was greater in older patients (41% vs 17%). The study database was not locked at the time of this analysis.Conclusions: InO was tolerable in older patients with relapsed/refractory ALL. Although OS was longer for younger patients versus older patients, InO demonstrated high response rates with similar DOR in the 2 age groups. Cancer 2018;124:1722-32. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The achievement of a sustained deep molecular response is a goal of increasing relevance because it opens the possibility of treatment discontinuation. The objective of this analysis was to develop a prediction model for a sustained molecular response with BCR-ABL1 level <0.0032% on the international scale (MR4.5 ) for at least 2 years according to BCR-ABL1 levels achieved within the first 12 months of therapy.Methods: Data for 603 patients with newly diagnosed chronic myeloid leukemia in chronic phase in consecutive prospective clinical trials were analyzed. The best fit average molecular response was defined by robust linear regression models, with which the average molecular levels were defined. The minimum acceptable molecular response was defined by quantile regression for the 95th percentile, with which the worst 5% BCR-ABL1 levels were identified.Results: In 603 patients with a median follow-up of 103 months, 2002 BCR-ABL1-level data points within 1 year of tyrosine kinase inhibitors were identified. The regression equation for the best fit average levels for a sustained MR4.5 was Log10 (PCR) = -0.1424 × (Months) - 0.8668, and the regression equation for minimum acceptable levels was Log10 (PCR) = -0.1403 × (Months) + 0.6142 (where PCR indicates polymerase chain reaction). To achieve a sustained MR4.5 , the best fit average levels were 0.051%, 0.019%, 0.007%, and 0.003% at 3, 6, 9, and 12 months, respectively; the minimum acceptable levels were 1.561%, 0.592%, 0.225%, and 0.085% at 3, 6, 9, and 12 months, respectively.Conclusions: This model proposes optimal values that predict the highest probability of reaching such a goal. These values can be used to guide therapy when a sustained MR4.5 is the objective. Cancer 2018;124:1160-8. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The outcome of older patients with newly diagnosed, Philadelphia chromosome (Ph)‐negative acute lymphoblastic leukemia (ALL) is poor. The combination of targeted therapy with low‐intensity chemotherapy is safe and effective. The objective of the current analysis was to compare the outcome of patients who received a combination of inotuzumab ozogamicin plus low‐intensity chemotherapy (mini–hyperfractionated cyclophosphamide, vincristine, and dexamethasone [mini‐HCVD]) with or without blinatumomab versus the outcome of those who received the standard, intensive, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) regimen. Methods: The authors analyzed 135 older patients with newly diagnosed, Ph‐negative ALL who were treated prospectively with standard HCVAD (n = 77) or with the combination of inotuzumab ozogamicin plus mini‐HCVD with or without blinatumomab (n = 58). A propensity score analysis was conducted using 1:1 matching using the nearest neighbor matching method. Results: Propensity score matching identified 38 patients in each cohort. The antibody plus low‐intensity chemotherapy combination induced higher response rates (98% vs 88%), with lower rates of early death (0% vs 8%) and lower rates of death in complete remission (5% vs 17%). With propensity score matching, the 3‐year event‐free survival rates for patients who received HCVAD and those who received the combination of inotuzumab ozogamicin plus mini‐HCVD with or without blinatumomab were 34% and 64%, respectively (P = .003), and the 3‐year overall survival rates were 34% and 63%, respectively (P = .004). By multivariate analysis, age (P = .019; hazard ratio, 1.045) and the combination of inotuzumab plus mini‐HCVD with or without blinatumomab (P = .020; hazard ratio, 0.550) were identified as independent prognostic factors for survival. Conclusions: The combination of inotuzumab ozogamicin plus mini‐HCVD with or without blinatumomab is safe and effective in older patients with newly diagnosed, Ph‐negative ALL and confers a better outcome compared with standard HCVAD chemotherapy. The combination of inotuzumab ozogamicin plus mini–hyperfractionated cyclophosphamide, vincristine, and dexamethasone with or without blinatumomab is safe and effective in older patients with newly diagnosed, Philadelphia chromosome‐negative acute lymphoblastic leukemia and confers a better outcome compared with standard hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Inotuzumab ozogamicin (InO) is an antibody-drug conjugate used for adults with relapsed/refractory B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The INotuzumab Ozogamicin trial to inVestigAte Tolerability and Efficacy (INO-VATE) previously reported improved outcomes with InO versus standard-of-care (SoC) chemotherapy. This article reports the final INO-VATE results (≥2 years of follow-up) and additional analyses of patient characteristics associated with improved outcomes.Methods: Between August 27, 2012, and January 4, 2015, this multicenter, parallel, open-label, phase 3 trial randomized 326 adults with relapsed/refractory ALL to InO (n = 164) or SoC (n = 162); 307 received 1 or more doses of the study drug (164 in the InO arm and 143 in the SoC arm).Results: The complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) rate was higher with InO versus SoC (73.8% vs 30.9%; 1-sided P < .0001), with consistent CR/CRi rates across patient subgroups. The median overall survival (OS) was 7.7 months with InO and 6.2 months with SoC, with 2-year OS rates of 22.8% and 10.0%, respectively (overall hazard ratio, 0.75; 97.5% confidence interval [CI], 0.57-0.99; 1-sided P = .0105). The predictors of OS with InO were the best minimal residual disease status, baseline platelet count, duration of first remission, achievement of CR/CRi, and follow-up hematopoietic stem cell transplantation (HSCT; all 2-sided P values < .05). More InO arm patients proceeded directly to HSCT after achieving CR/CRi before any follow-up induction therapy (39.6% [95% CI, 32.1%-47.6%] vs 10.5% [6.2%-16.3%]; 1-sided P < .0001). The most frequent all-grade and grade 3 or higher adverse events in both arms were hematologic. Veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) was more frequent with InO (23 of 164 [14.0%] vs 3 of 143 [2.1%]).Conclusions: In patients with relapsed/refractory BCP ALL in INO-VATE, InO was associated with a greater likelihood of CR/CRi across key patient subgroups, and it served as a bridge to HSCT. Potential VOD/SOS risk factors must be considered when InO treatment decisions are being made. [ABSTRACT FROM AUTHOR]

Background: The outcomes of patients with relapsed or refractory (R-R) acute lymphoblastic leukemia (ALL) are poor. Inotuzumab ozogamicin and blinatumomab have single-agent activity in R-R ALL. Their addition to low-intensity chemotherapy may further improve the outcomes of patients with ALL in their first relapse.Methods: The chemotherapy was lower in intensity than conventional hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone and was called mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone (or mini-HCVD). Inotuzumab was given on day 3 of each of the first 4 cycles at 1.8 to 1.3 mg/m2 for cycle 1, and this was followed by 1.3 to 1.0 mg/m2 for subsequent cycles. From patient 39 onward, the inotuzumab dose was reduced and fractionated into weekly doses (0.6 and 0.3 mg/m2 during cycle 1 and 0.3 and 0.3 mg/m2 during subsequent cycles), and blinatumomab was administered for up to 4 cycles after inotuzumab therapy.Results: Forty-eight patients with Philadelphia chromosome-negative ALL with a median age of 39 years were treated during their first relapse. Overall, 44 patients (92%) responded, with 35 of them (73%) achieving a complete response. The overall minimal residual disease negativity rate among the responders was 93%. Twenty-four patients (50%) underwent allogeneic stem cell transplantation (ASCT). Veno-occlusive disease of any grade occurred in 5 patients (10%). With a median follow-up of 31 months, the median progression-free survival (PFS) and the median overall survival (OS) were 11 and 25 months, respectively. The 2-year PFS and OS rates were 42% and 54%, respectively. Of the 24 patients (50%) who underwent ASCT, 14 patients were alive at the last follow-up (13 [54%] in remission). Of the remaining 20 responding patients who did not undergo subsequent ASCT, 6 (30%) remained in remission at the last follow-up. According to propensity score matching, the combination of mini-HCVD and inotuzumab with or without blinatumomab conferred better outcomes than intensive salvage chemotherapy or inotuzumab alone.Conclusions: The combination of inotuzumab and low-intensity mini-HCVD chemotherapy with or without blinatumomab shows encouraging results in patients with ALL in first salvage. [ABSTRACT FROM AUTHOR]

Background: The prognosis is poor for patients who have relapsed-refractory acute myelogenous leukemia (AML). Most published reports analyzed results from therapies in first-salvage AML or in studies that were conducted before 2000. Several novel agents and strategies are being tested for potential approval as treatment for patients with relapsed-refractory AML in second salvage. Therefore, it is important to establish the historic results of anti-AML therapies in this setting in the modern era. The objective of the current study was to analyze the results from second salvage therapies in patients with AML since 2000 with regard to response and survival.Methods: In total, 673 patients who received second salvage therapies for AML since 2000 were analyzed. Their median age was 60 years (range, 18-89 years). Salvage therapy consisted of cytarabine-based regimens in 267 patients, noncytarabine combinations in 37, hypomethylating agent-based regimens in 136, and phase 1 and 2 single agents in 233.Results: Eighty-six of the 673 patients (13%) achieved a complete response (CR) or a CR with low platelet count (CRp). The median duration of CR-CRp was 7.2 months. The median survival was 4.4 months (95% confidence interval, 4.0-4.8 months), and the 1-year survival rate was 16% (95% confidence interval, 14%-19%). Multivariate analysis identified the following as independent adverse factors for achievement of CR-CRp: platelets < 50 × 109 /L (P < .001), complex karyotype with ≥3 chromosomal abnormalities (P = .02), regimens that did not include cytarabine or hypomethylating agents (P = .014), and no prior CR lasting ≥12 months with frontline or salvage 1 therapies (P < .001). The independent adverse factors associated with worse survival were age ≥60 years (P = .01), platelets < 50 × 109 /L (P = .02), peripheral blasts ≥ 20% (P = .03), albumin ≤ 3 g/dL (P = .04), and complex karyotype (P = .003). The authors also applied and validated, in the current population, the 2 multivariate-derived prognostic models for CR and survival developed in their previous study of 594 patients who received treatment for second salvage AML from the previous 2 decades.Conclusions: This large-scale analysis establishes the modern historic results of second salvage therapy in AML and validates the prognostic models associated with outcome. These data could be used to analyze the differential benefits of current or future investigational strategies under evaluation in this setting and for the purpose of potential approval of new agents in the United States and the world. Cancer 2018;124:2534-40. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Outcomes in patients with chronic myeloid leukemia in blast phase (CML-BP) are historically dismal. Herein, the authors sought to analyze the characteristics, prognostic factors, and survival outcomes in patients with CML-BP in the tyrosine kinase inhibitor (TKI) era.Methods: A total of 477 patients with CML-BP were treated with a TKI at some point during the course of their CML. Cox proportional hazard models identified characteristics that were predictive of survival. Overall survival and failure-free survival were assessed. Optimal cutoff points for specific parameters were identified using classification and regression tree (CART) analysis.Results: The median age of the patients was 53 years (range, 16-84 years) and 64% were male. Approximately 80% of patients initially were diagnosed in the chronic phase of CML at a median of 41 months (range, 0.7-298 months) before transformation to CML-BP. De novo CML-BP occurred in 71 patients. Approximately 72% of patients received TKI therapy before CML-BP. The initial therapy for CML-BP included a TKI alone (35%), a TKI with chemotherapy (46%), and non-TKI therapies (19%). The median overall survival was 12 months and the median failure-free survival was 5 months. In multivariate analysis, myeloid immunophenotype, prior TKI, age ≥58 years, lactate dehydrogenase level ≥1227 IU/L, platelet count < 102 K/μL, no history of stem cell transplantation, transition to BP from chronic phase/accelerated phase, and the presence of chromosome 15 aberrations predicted for a significantly increased risk of death. Achievement of major hematologic response and/or complete cytogenetic response to first-line treatment was found to be predictive of better survival. The combination of a TKI with intensive chemotherapy followed by stem cell transplantation appeared to confer the best outcome.Conclusions: Patients with CML-BP continue to pose a therapeutic challenge, have dismal outcomes, and require newer treatment approaches. Cancer 2017;123:4391-402. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML).Methods: Herein, the authors evaluated the efficacy and safety of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients). Patients received induction with idarubicin and cytarabine, plus either clofarabine or fludarabine. Responding patients could receive up to 6 cycles of consolidation therapy. Outcomes were compared with a historical cohort of patients who received idarubicin and cytarabine.Results: The complete remission/complete remission without platelet recovery rate was similar among patients in the CIA and FIA arms (80% and 82%, respectively). The median event-free survival was 13 months and 12 months, respectively (P = .91), and the median overall survival was 24 months and not reached, respectively (P = .23), in the 2 treatment arms. CIA was associated with more adverse events, particularly transaminase elevation, hyperbilirubinemia, and rash. Early mortality was similar in the 2 arms (60-day mortality rate of 4% for CIA vs 1% for FIA; P = .32). In an exploratory analysis of patients aged <50 years, FIA was found to be associated with improved survival compared with idarubicin and cytarabine (2-year event-free survival rate: 58% vs 30% [P = .05] and 2-year overall survival rate: 72% vs 36% [P = .009]).Conclusions: CIA and FIA have similar efficacy in younger patients with newly diagnosed AML, although FIA is associated with a better toxicity profile. Cancer 2017;123:4430-9. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) in the adolescent and young adult (AYA) population is a difficult clinical problem. The AYA population, generally regarded as patients aged 15 to 39 years, currently draws a good deal of attention, particularly in the area of therapy selection. The current trend is to treat this group of patients with leukemia regimens based on pediatric protocols, and results comparing pediatric approaches versus adult approaches to treatment are maturing. Results are pending from a large US trial in which pediatric-based treatment is given to AYA patients with ALL. In tandem with these new clinical trials, researchers have reported disease features in the AYA group that may explain some of the differences in response to treatment observed in the AYA population compared with the pediatric population. In addition, unique social factors in this age group add to the complexity of ALL therapy in the AYA population. AYA patients are developing independence and separating from their parents. They tend to be noncompliant. Young adults suffer from a lack of health care insurance and poor access to clinical trials, and have specific concerns regarding toxicities, in particular fertility. Cancer 2017;123:2398-403. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Ibrutinib is a Bruton tyrosine kinase inhibitor and is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) in frontline and relapsed/refractory settings. The authors previously reported poor outcomes for patients who discontinued ibrutinib; however, long-term outcomes were not reported.Methods: Data from 320 patients who received ibrutinib on clinical studies between 2010 and 2015 at The University of Texas MD Anderson Cancer Center were retrospectively analyzed.Results: Long-term outcomes among patients with CLL after they discontinued ibrutinib were analyzed. Ninety of 320 patients (28%) who were treated on ibrutinib-based regimens discontinued ibrutinib. Of these, 80 had relapsed/refractory disease, and 10 were treatment-naive. The median time to discontinuation was 15 months (range, 1.2-54 months). After a median follow-up of 38 months after starting ibrutinib, 40 patients (44%) remained alive. Major reasons for ibrutinib discontinuation were intolerance (n = 29; 32%), miscellaneous (n = 28; 31%), progression (n = 19; 21%), and Richter transformation (RT) (n = 9; 10%). The median survival according to the reason for discontinuation was 33 months for ibrutinib intolerance, 11 months for miscellaneous causes, 16 months for progressive CLL, and 2 months for RT. Among the 19 patients who had progressive CLL, 42% responded to subsequent therapy.Conclusions: Ibrutinib discontinuation was observed during therapy. Patients with CLL who had disease transformation had especially poor outcomes, whereas those who developed progressive disease during ibrutinib therapy had a median survival of <1.5 years. Survival was associated with the reason for discontinuation; patients who had progressive CLL had better survival compared with those who had disease transformation. Effective salvage strategies for patients with CLL who progress on ibrutinib therapy is of critical importance. Cancer 2017;123:2268-2273. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Some patients with chronic myeloid leukemia (CML) have a history of previous malignancies. To the authors' knowledge, outcomes for CML diagnosed in these patients have not been well described. The current study was conducted to determine the outcome of patients with CML and a history of prior malignancies.Methods: The current study included patients who were enrolled in clinical trials of tyrosine kinase inhibitors as initial therapy for CML in chronic phase from July 2000 to January 2014.Results: Of the 630 patients with CML who were treated with frontline tyrosine kinase inhibitors, 626 had a known prior malignancy status. Of these, 45 patients (7%) had a prior malignancy other than nonmelanoma skin cancer whereas 17 patients (3%) had a history of nonmelanoma skin cancers alone. Characteristics of CML were similar between the patients with no prior malignancy, those with a prior malignancy, and those with nonmelanoma skin cancer. Patients with a prior malignancy were found to have an older median age compared with the other 2 groups. The most common prior malignancies were nonmelanoma skin cancer in 20 patients, breast cancer in 11 patients, melanoma in 7 patients, prostate cancer in 6 patients, and colorectal cancer in 5 patients. With regard to CML, the event-free survival, transformation-free survival, and failure-free survival rates were found to be similar between the groups. There was a statistically significantly decreased survival in the group with a prior malignancy versus the group with no prior malignancy versus the group with nonmelanoma skin cancer. In a multivariate analysis, advanced age and an elevated creatinine level were found to be associated with worse survival after a diagnosis of CML.Conclusions: Patients with CML with a history of prior malignancies appear to have the same excellent outcome as patients with no prior malignancies. In the few instances in which concomitant therapy for other malignancies was required during therapy with tyrosine kinase inhibitors, this was able to be accomplished without significant toxicity. Cancer 2017;123:609-616. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The introduction of novel prognostic factors such as minimal residual disease (MRD) and genomic profiling has led to the reevaluation of the role of cytogenetics and other conventional factors in risk stratification for acute lymphoblastic leukemia (ALL).Methods: This study assessed the impact of baseline cytogenetics on the outcomes of 428 adult patients with Philadelphia chromosome-negative ALL who were receiving frontline chemotherapy. Three hundred thirty patients (77%) were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone-based regimens, and 98 (23%) were treated with the augmented Berlin-Frankfurt-Munster regimen.Results: The median age was 40 years (range, 13-86 years). One hundred eighty-six patients (43%) had diploid cytogenetics, 32 (7%) had complex cytogenetics (defined as ≥ 5 chromosomal abnormalities), 27 (6%) had low hypodiploidy/near-triploidy (Ho-Tr), 24 (6%) had high hyperdiploidy, and 24 (6%) had a mixed-lineage leukemia (MLL) rearrangement. Patients with an MLL rearrangement, Ho-Tr, or a complex karyotype had significantly worse relapse-free survival (RFS) and overall survival (OS) than the diploid group. According to a multivariate analysis including all the baseline characteristics and MRD status, Ho-Tr and a complex karyotype were independent predictive factors for worse RFS and OS. Furthermore, survival among all cytogenetic groups was similar, regardless of the treatment received.Conclusions: A complex karyotype and Ho-Tr are adverse prognostic factors for adults with ALL independently of the MRD status. These findings suggest that pretreatment cytogenetics remain a valuable prognostic tool in this population. Cancer 2017;123:459-467. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Minimal residual disease (MRD) assessment predicts survival for patients with newly diagnosed acute lymphoblastic leukemia (ALL). Its significance in relapsed/refractory ALL is less clear.Methods: This study identified 78 patients with relapsed/refractory B-cell ALL who achieved a morphologic response with inotuzumab ozogamicin (n = 41), blinatumomab (n = 11), or mini-hyperfractionated cyclophosphamide, vincristine, and doxorubicin plus inotuzumab (n = 26) during either salvage 1 (S1; n = 46) or salvage 2 (S2; n = 32) and had undergone an MRD assessment by multiparameter flow cytometry at the time of remission.Results: MRD negativity was achieved in 41 patients overall (53%). The MRD negativity rate was 57% in S1 and 47% in S2. Among patients in S1, achieving MRD negativity was associated with longer event-free survival (EFS; median, 18 vs 7 months; 2-year EFS rate, 46% vs 17%; P = .06) and overall survival (OS; median, 27 vs 9 months; 2-year OS, 52% vs 36%; P = .15). EFS and OS were similar in S2, regardless of the MRD response. Among MRD-negative patients who underwent allogeneic stem cell transplantation (SCT), EFS and OS were superior for those who underwent SCT in S1 rather than S2 (P = .003 and P = .04, respectively). Patients in S1 who achieved MRD negativity and subsequently underwent SCT had the best outcomes with a 2-year OS rate of 65%.Conclusions: Patients with relapsed/refractory ALL who achieve MRD negativity in S1 can have long-term survival. Patients in S2 generally have poor outcomes, regardless of their MRD status. Cancer 2017;123:294-302. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The role of day 14 (D14) bone marrow (BM) assessment in detecting increased blasts in patients undergoing induction for acute lymphoblastic leukemia (ALL) is not well defined.Methods: This study evaluated 389 adolescent and adult patients with previously untreated Philadelphia chromosome-negative ALL who received frontline induction chemotherapy and for whom a D14 BM assessment was performed.Results: A D14 BM blast proportion < 10% (including blast-free aplastic BM) was observed in 319 patients (82%), 10% to 29% was observed in 31 patients (8%), and ≥30% was observed in 39 patients (10%). The composite complete remission (CR)/complete remission with inadequate platelet recovery (CRp) rates for these groups were 99.7%, 87%, and 79%, respectively. The median event-free survival (EFS) was 49, 33, and 9 months, respectively (P < .001). The median overall survival (OS) was 88, 37, and 21 months, respectively (P < .001). The D14 BM blast group was the only factor predictive for the achievement of CR/CRp (P < .001). According to a multivariate analysis, the D14 BM blast group was independently prognostic for both EFS (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.12-1.85; P = .004) and OS (HR, 1.45; 95% CI, 1.14-1.85; P = .003). However, when minimal residual disease (MRD) assessment at the time of CR was added to the model, the D14 BM blast group was no longer prognostic for EFS or OS.Conclusions: An assessment of residual D14 BM blasts in patients with ALL is highly predictive of the achievement of CR with induction chemotherapy and of EFS and OS. However, the D14 BM blast assessment is less prognostic of long-term outcomes when an MRD assessment is also available. Cancer 2016;122:3812-3820. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The clinical efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) plus ponatinib has not been compared with that of HCVAD plus dasatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in a randomized clinical trial.Methods: The authors analyzed 110 patients with newly diagnosed Ph+ ALL who were enrolled in 2 consecutive, prospective, phase 2 clinical trials of frontline HCVAD with either dasatinib (63 patients) or ponatinib (47 patients). Propensity score analysis with 1:1 matching with the nearest neighbor matching method and inverse probability of treatment weighting (IPTW) analysis based on the propensity scores were performed to assess response rates, event-free survival (EFS), and overall survival (OS) between the cohorts.Results: Propensity score matching identified 41 patients in each cohort. With propensity score matching, the 3-year EFS rates for patients treated with HCVAD plus ponatinib and HCVAD plus dasatinib were 69% and 46%, respectively (P =.04), and the 3-year OS rates were 83% and 56%, respectively (P =.03). IPTW analysis using prematching cohorts demonstrated that patients treated with HCVAD plus ponatinib had significantly higher rates of minimal residual disease negativity by flow cytometry on day 21, complete cytogenetic response at complete response, major molecular response at complete response and at 3 months, and complete molecular response at 3 months. IPTW confirmed that treatment with HCVAD plus ponatinib was associated with longer EFS (P =.003) and OS (P =.001) compared with treatment with HCVAD plus dasatinib.Conclusions: The clinical outcome of patients treated with HCVAD plus ponatinib appears to be superior to that of patients treated with HCVAD plus dasatinib among individuals with Ph+ ALL. Cancer 2016;122:3650-6. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: More active therapies are needed for older and unfit patients with chronic lymphocytic leukemia (CLL) who are not eligible for chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The phosphyotidylinositol-3-kinase δ inhibitor idelalisib is effective in patients with treatment-naive and relapsed/refractory CLL as monotherapy and in combination with rituximab, but it can be associated with treatment-limiting adverse events, particularly diarrhea/colitis. The outcomes for patients who cease treatment for adverse events have not been previously described.Methods: The authors analyzed long-term follow-up data from 40 treatment-naïve patients aged ≥65 years who received treatment at The University of Texas MD Anderson Cancer Center on a phase 2 study of idelalisib plus rituximab for CLL.Results: In patients who permanently ceased treatment because of toxicity, the time to subsequent disease progression was analyzed according to baseline characteristics. Fifteen patients permanently ceased therapy (PCT) because of toxicity (PCTTOX ), most commonly diarrhea/colitis (n = 7), at a median of 11 months after commencing treatment. PCTTOX was associated with a higher risk of subsequent disease progression (hazard ratio, 6.61; 95% confidence interval, 1.77-16.15) relative to that observed in patients who remained on therapy. Ten patients subsequently progressed, and 7 required salvage therapy; 5 patients remained progression-free at a median of 23.3 months (range, 8.5-28.6 months). Patients who were positive for ζ-associated protein-70 had more rapid disease progression after treatment cessation (P = .048). There were no CLL-related deaths.Conclusions: PCTTOX is the major determinant of PFS in patients who receive first-line idelalisib-based treatment. However, a subgroup of patients with favorable biologic characteristics has prolonged PFS, even after PCTTOX . The absence of CLL-related deaths indicates that salvage treatment is generally successful after PCTTOX . Cancer 2016;122:2505-11. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: A high pretreatment β2 -microglobulin (B2M) level is associated with inferior survival outcomes in patients with chronic lymphocytic leukemia. However, to the authors' knowledge, the prognostic and predictive significance of changes in B2M during treatment have not been reported to date.Methods: The authors analyzed 83 patients treated with ibrutinib-based regimens (66 with recurrent/refractory disease) and 198 treatment-naive patients who were treated with combined fludarabine, cyclophosphamide, and rituximab (FCR) to characterize changes in B2M and their relationship with clinical outcomes.Results: B2M rapidly decreased during treatment with ibrutinib; on multivariable analysis, patients who received FCR (odds ratio, 0.40; 95% confidence interval [95% CI], 0.18-0.90 [P = .027]) were less likely to have normalized B2M at 6 months than patients treated with ibrutinib. On univariable analysis, normalization of B2M was associated with superior progression-free survival (PFS) from the 6-month landmark in patients treated with ibrutinib-based regimens and FCR. On multivariable analysis, failure to achieve normalized B2M at 6 months of treatment was associated with inferior PFS (hazard ratio, 16.9; 95% CI, 1.3-220.0 [P = .031]) for patients treated with ibrutinib, after adjusting for the effects of baseline B2M, stage of disease, fludarabine-refractory disease, and del(17p). In contrast, in patients treated with FCR, negative minimal residual disease status in the bone marrow was the only variable found to be significantly associated with superior PFS (hazard ratio, 0.28; 95% CI, 0.12-0.67 [P = .004]).Conclusions: Normalization of B2M at 6 months in patients treated with ibrutinib was found to be a useful predictor of subsequent PFS and may assist in clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: Tyrosine kinase inhibitors (TKIs) significantly improve survival in patients with chronic myeloid leukemia in chronic phase (CML-CP). Conditional probability provides survival information in patients who have already survived for a specific period of time after treatment.Methods: Cumulative response and survival data from 6 consecutive frontline TKI clinical trials were analyzed. Conditional probability was calculated for failure-free survival (FFS), transformation-free survival (TFS), event-free survival (EFS), and overall survival (OS) according to depth of response within 1 year of the initiation of TKIs, including complete cytogenetic response, major molecular response, and molecular response with a 4-log or 4.5-log reduction.Results: A total of 483 patients with a median follow-up of 99.4 months from the initiation of treatment with TKIs were analyzed. Conditional probabilities of FFS, TFS, EFS, and OS for 1 additional year for patients alive after 12 months of therapy ranged from 92.0% to 99.1%, 98.5% to 100%, 96.2% to 99.6%, and 96.8% to 99.7%, respectively. Conditional FFS for 1 additional year did not improve with a deeper response each year. Conditional probabilities of TFS, EFS, and OS for 1 additional year were maintained at >95% during the period.Conclusions: In the era of TKIs, patients with chronic myeloid leukemia in chronic phase who survived for a certain number of years maintained excellent clinical outcomes in each age group. Cancer 2016;122:238-248. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The long-term efficacy of a combination of chemotherapy and dasatinib in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is not well established.Methods: Patients received dasatinib with 8 cycles of alternating hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and high-dose cytarabine and methotrexate. Patients in complete remission (CR) continued maintenance dasatinib, vincristine, and prednisone for 2 years, which was followed by dasatinib indefinitely. Patients eligible for allogeneic stem cell transplantation (SCT) received it during their first CR.Results: Seventy-two patients with a median age of 55 years (range, 21-80 years) were treated; 69 (96%) achieved CR. Among them, 57 (83%) achieved cytogenetic CR after 1 cycle, and 64 (93%) achieved a major molecular response at a median of 4 weeks (range, 2-38 weeks). Sixty-five patients (94%) were negative for minimal residual disease assessed by flow cytometry at a median of 3 weeks (range, 2-37 weeks). Dasatinib-related grade 3 and 4 adverse events included bleeding, pleural/pericardial effusions, and elevated transaminases. With a median follow-up of 67 months (range, 33-97 months), 33 patients (46%) were alive, and 30 (43%) were in CR; 12 underwent allogeneic SCT. Thirty-nine patients died (3 at induction, 19 after relapse, 7 after SCT performed during first CR, and 10 during CR). The median disease-free survival and overall survival were 31 (range, 0.3-97 months) and 47 months (range, 0.2-97 months), respectively. Seven relapsed patients had BCR-ABL kinase domain mutations, including 4 with T315I.Conclusions: A combination of chemotherapy with dasatinib is effective in achieving long-term remission for patients with newly diagnosed Ph + ALL. [ABSTRACT FROM AUTHOR]

Background: Chronic use of tyrosine kinase inhibitors (TKIs) may lead to previously unrecognized adverse events. This study evaluated the incidence of acute kidney injury (AKI) and chronic kidney disease (CKD) in chronic-phase (CP) chronic myeloid leukemia (CML) patients treated with imatinib, dasatinib, and nilotinib.Methods: Four hundred sixty-eight newly diagnosed CP CML patients treated with TKIs were analyzed. The molecular and cytogenetic response data, creatinine, and glomerular filtration rate (GFR) were followed from the start of therapy to the last follow-up (median, 52 months). GFR was estimated with the Modification of Diet in Renal Disease equation.Results: Nineteen patients (4%) had TKI-associated AKI. Imatinib was associated with a higher incidence of AKI in comparison with dasatinib and nilotinib (P = .014). Fifty-eight patients (14%) developed CKD while they were receiving a TKI; 49 of these patients (84%) did so while they were being treated with imatinib (P < .001). Besides imatinib, age, a history of hypertension, and diabetes mellitus were also associated with the development of CKD. In patients with no CKD at the baseline, imatinib was shown to reduce GFR over time. Interestingly, imatinib did not cause a significant decline in the GFRs of patients with a history of CKD. Imatinib, dasatinib, and nilotinib increased the mean GFR after 3 months of treatment, and nilotinib led with the most significant increase (P < .001). AKI or CKD had no significant impact on overall cytogenetic and molecular response rates or survival.Conclusions: The administration of TKIs may be safe in the setting of CKD in CP CML patients, but close monitoring is still warranted. [ABSTRACT FROM AUTHOR]

Background: Fludarabine, cyclophosphamide, and rituximab (FCR) result in durable responses in patients with previously untreated chronic lymphocytic leukemia (CLL). Previous reports have suggested that in patients with relapsed CLL, a dose-intensified rituximab regimen increases response rates in comparison with standard-dose rituximab. It is unknown whether rituximab intensification of the FCR regimen will result in improved response rates and patient outcomes in patients with previously untreated CLL.Methods: A single-arm study was conducted to evaluate the safety and efficacy of a modified FCR regimen with multiple-dose rituximab (FCR3) in 65 patients with previously untreated CLL. The results were compared with those for a historical cohort treated with FCR.Results: The overall response rate to FCR3 was 97%, with 75% of the patients achieving a complete remission. Minimal residual disease negativity was achieved for 62% of the patients according to flow cytometry. The median time to progression (TTP) was 81 months, and the median overall survival (OS) was not reached, with 58% of the patients still alive at a median survivor follow-up of 9.7 years. Grade 3 or 4 neutropenia, grade 3 or 4 thrombocytopenia, and major infections were observed with 45%, 5%, and 1.9% of the FCR3 courses, respectively. Therapy-related myelodysplastic syndrome (t-MDS) or therapy-related acute myelogenous leukemia (t-AML) developed in 7 patients (11%; P < .01 vs the historical FCR cohort).Conclusions: In patients with previously untreated CLL, FCR3 resulted in response rates, TTP, and OS similar to those of a historical cohort of patients treated with FCR. FCR3 was associated with an increased incidence of t-MDS/t-AML. [ABSTRACT FROM AUTHOR]

Background: Ibrutinib is active in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). In patients treated with ibrutinib for R/R CLL, del(17p), identified by interphase fluorescence in situ hybridization (FISH), is associated with inferior progression-free survival despite equivalent initial response rates. Del(17p) is frequently associated with a complex metaphase karyotype (CKT); the prognostic significance of CKT in ibrutinib-treated patients has not been reported.Methods: This study reviewed 88 patients treated for R/R CLL at The University of Texas MD Anderson Cancer Center with investigational ibrutinib-based regimens from 2010 to 2013. Pretreatment FISH and lipopolysaccharide-stimulated metaphase cytogenetic analysis were performed on bone marrow.Results: An adequate pretreatment metaphase karyotype was available for 56 of the 88 patients. The karyotype was complex in 21 of the 56 cases; 17 of the 21 had del(17p) according to FISH. The overall response rate, including partial remission with persistent lymphocytosis, was 94%; 18% had complete responses. In a multivariate analysis (MVA), only CKT was significantly associated with event-free survival (EFS; hazard ratio [HR], 6.6 [95% CI 1.7-25.6]; P = .006). Fludarabine-refractory CLL (HR, 6.9 [95% CI 1.8-27.1], P = .005) and CKT (HR 5.9 [95% CI 1.6-22.2], P = .008) were independently associated with inferior overall survival (OS) in MVA. Del(17p) by FISH was not significantly associated with EFS or OS in MVA.Conclusions: CKT is a powerful predictor of outcomes for ibrutinib-treated patients with R/R CLL and may be a stronger predictor of biological behavior than del(17p) by FISH. Because of their relatively poor outcomes, patients with CKT are ideal candidates for studies of consolidative treatment strategies or novel treatment combinations. [ABSTRACT FROM AUTHOR]

Significant advances have been made in the last decade toward a better understanding of the disease pathogenesis and the development of novel therapies that target specific subsets of adult acute lymphoblastic leukemia (ALL). Risk-adapted strategies are transforming the disease treatment and prognosis. With current treatment regimens, long-term survival is achieved by approximately 50% of patients with B-cell ALL, 50% to 60% of patients with Philadelphia chromosome-positive ALL, and approximately 80% of patients with Burkitt's leukemia. Genomic profiling in ALL has identified new prognostic markers, new therapeutic targets, and novel ALL subtypes. These may be amenable to future targeted therapies that can further improve outcomes. The early recognition of early precursor T-cell ALL, a distinct pathobiological entity with a poor prognosis, is essential for the development of an effective clinical management strategy. The role of monoclonal antibodies and cytotoxic T-cell therapies continues to be defined. Many of the approaches are currently being evaluated for ALL salvage. Their incorporation into frontline adult ALL therapy, in concomitant or sequential strategies, may increase the cure rates to levels achieved in pediatric ALL and may reduce the need for prolonged intensive and maintenance chemotherapy. Cancer 2015;121:2517-2528. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND The hypomethylating agents (HMAs) azacitidine and decitabine are most commonly used to treat patients with higher-risk myelodysplastic syndromes (MDS). To the authors' knowledge, the prognosis of patients with low-risk and intermediate-1-risk MDS by the International Prognostic Scoring System (IPSS) after HMA failure has not been explored comprehensively. METHODS The clinical characteristics and treatment outcome of 438 patients with low-risk and intermediate-1-risk MDS who were treated with HMAs were retrospectively analyzed. RESULTS Using the International Working Group response criteria, the overall objective response to HMA was 35% with a median of 6 cycles of HMA administered, and the median response duration was 7 months. Only 7% of patients had disease that transformed into acute myeloid leukemia while receiving therapy. Of the 290 patients who were evaluable at the time of HMA failure, 77% remained in the lower-risk disease categories. On multivariate analysis, baseline neutropenia, intermediate-risk and poor-risk baseline karyotype, and lack of response to HMA were found to be independently associated with a higher risk of disease progression. With a median follow-up of 16 months, the median transformation-free survival and overall survival (OS) after HMA failure were 15 months and 17 months, respectively. On multivariate analysis, only The University of Texas MD Anderson Global Scoring System was found to be independently predictive of outcome, with patients with higher-risk categories having poor transformation-free survival (hazards ratio [HR], 1.5; P = .003) and OS (HR, 1.8; P = .002). The administration of salvage therapy was independently associated with better OS only (HR, 0.8; P = .01). CONCLUSIONS Outcomes of patients with lower-risk MDS after HMA failure are poor and the treatment of these patients remains an unmet medical need. OS is a reasonable primary endpoint for clinical studies targeting this population. Cancer 2015;121:876-882. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Various trials have reported improved outcomes for adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) who received treatment with pediatric-based regimens. Those reports prompted the current investigation of the pediatric augmented Berlin-Frankfurt-Münster (ABFM) regimen in AYA patients. The results were compared with those from a similar population that received the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen.Methods: Eighty-five patients ages 12 to 40 years who had Philadelphia chromosome (Ph)-negative ALL received the ABFM regimen from October 2006 through April 2012. Their outcome was compared with outcomes in 71 historic AYA patients who received hyper-CVAD from the authors' institution. Patient and disease characteristics, as well as minimal residual disease status, were analyzed for their impact on outcomes.Results: The complete response rate with ABFM was 94%. The 3-year complete remission duration (CRD) and overall survival (OS) rates were 70% and 74%, respectively. For patients aged ≤21 years, the 3-year CRD and OS rates were 72% and 85%, respectively; and, for patients ages 21 to 40 years, the respective rates were 69% and 60%. The initial white blood cell count was an independent predictive factor of OS and CRD. The minimal residual disease status on days 29 and 84 of therapy also were predictive of long-term outcomes. Severe regimen toxicities included transient hepatotoxicity in 35% to 39% of patients, pancreatitis in 11% of patients, osteonecrosis in 11% of patients, and thrombosis in 22% of patients. The 3-year OS rate was 74% in the ABFM group versus 71% in the hyper-CVAD group, and the corresponding 3-year CRD rate was 70% versus 66%, respectively.Conclusions: ABFM was tolerable in AYA patients with ALL but was not associated with significant improvements in CRD and OS compared with hyper-CVAD. [ABSTRACT FROM AUTHOR]

BACKGROUND Patients with relapsed chronic lymphocytic leukemia (CLL) often achieve response with chemoimmunotherapy but have short remission durations. Studies have shown that patients with CLL have increased angiogenesis in the microenvironment; levels of proangiogenic growth factors such as VEGF and/or angiopoietin-2 are also elevated. Increased angiogenesis correlates with poor outcome in CLL. Bevacizumab (B) is a humanized monoclonal antibody targeting VEGF-A. METHODS In this study, we analyzed whether a combination of bevacizumab with fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy (FCR-B) could improve outcomes in patients with relapsed CLL. Sixty-two patients were enrolled. The median age of the patients was 60 years (range, 31-84 years) and 40% had received >1 prior therapy for CLL. Sixty-one patients were evaluable for toxicity, and 57 were evaluable for response. Six cycles were planned; 36 patients (59%) completed ≥4-6 cycles of the regimen. RESULTS The overall response rate was 79%, with 13 (23%) complete remissions (CRs), 8 nodular partial remissions (14%), and 24 partial remissions (43%). The median progression-free survival and overall survival rates were 13.5 and 45 months, respectively. Grade 3 or 4 toxicities included febrile neutropenia (n = 40), infections (n = 21), thrombocytopenia (n = 18) and anemia (n = 9). CONCLUSIONS Results with FCR-B were similar to those observed with an historical cohort of relapsed patients treated with FCR. Cancer 2014;120:3494-3501. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND The authors developed an ex vivo methodology to perform drug library screening against human leukemia. METHODS The strategy for this screening relied on human blood or bone marrow cultures under hypoxia; under these conditions, leukemia cells deplete oxygen faster than normal cells, causing a hemoglobin oxygenation shift. Several advantages were observed: 1) partial recapitulation of the leukemia microenvironment, 2) use of native hemoglobin oxygenation as a real-time sensor/reporter, 3) cost-effectiveness, 4) species specificity, and 5) a format that enables high-throughput screening. RESULTS For a proof of concept, a chemical library (size, approximately 20,000 compounds) was screened against human leukemia cells. Seventy compounds were identified ('hit' rate, 0.35%; Z-factor = 0.71) that had activity, and 20 compounds were examined to identify 18 true-positive compounds (90%). Finally, the results demonstrated that carbonohydraxonic diamide group-containing compounds are potent antileukemia agents that induce cell death in leukemia cells and in patient-derived samples. CONCLUSIONS The current results indicated that this unique functional assay can identify novel drug candidates and can help with the development of future applications in personalized drug selection for patients with leukemia. Cancer 2014;120:589-602. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Chronic myeloid leukemia (CML) may progress to blast phase (BP) at the rate of 1% to 1.5% per year. With the use of single-agent tyrosine kinase inhibitors, median overall survival ranges between 7 and 11 months. METHODS The outcome was analyzed for 42 patients with lymphoid BP-CML who were treated with hyperfractionated cyclophosphamide, vincristine, Adriamycin, dexamethasone (HCVAD) plus imatinib or dasatinib. RESULTS Complete hematological response was achieved in 90% of patients, complete cytogenetic remission in 58%, and complete molecular remission in 25%. Flow cytometry minimal residual disease negativity was achieved by 42% of evaluable patients after induction. Eighteen patients received allogeneic stem cell transplant (SCT) while in first complete hematological response. Median remission duration was 14 months and was longer among SCT recipients ( P = .01) on multivariate analysis. Median overall survival was 17 months (range, 7-27 months) and was longer among SCT recipients ( P < .001) and patients treated with dasatinib ( P = .07) on multivariate analysis. Although a high rate of hematologic toxicity (100%) and infectious complications (59%) were observed, the related rate of treatment discontinuation was low (7% and 9%, respectively). CONCLUSIONS HCVAD combined with tyrosine kinase inhibitors is an effective regimen for the management of BP-CML, particularly when followed by allogeneic SCT. Cancer 2014;120:373-380 © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The combination of fludarabine, cyclophosphamide, and rituximab (FCR) has produced improved response rates and a prolonged survival in patients with chronic lymphocytic leukemia (CLL). However, its therapeutic power is counterbalanced by significant hematologic toxicity. Persistent and new-onset cytopenia after the completion of FCR raise concern about disease recurrence, the development of therapy-related myeloid malignancies (TRMM), and infections.Methods: A total of 207 patients with CLL who achieved complete response, complete response with incomplete bone marrow recovery, or nodular partial remission were analyzed after frontline FCR therapy.Results: Three months after the completion of therapy, 35% of patients had developed grade 2 to 4 cytopenia (according to Common Terminology Criteria for Adverse Events [version 4.0]). Factors found to be associated with cytopenia at 3 months after therapy were older age, advanced Rai stage disease, and lower baseline blood counts. Moreover, patients with cytopenia were less likely to have completed 6 courses of therapy with FCR. At 6 months and 9 months after therapy, the prevalence of grade 2 to 4 cytopenia was 24% and 12%, respectively. No differences in progression-free survival and overall survival were noted between cytopenic and noncytopenic patients or between patients with persistent and new-onset cytopenia. The prevalence of TRMM was 2.3% and did not differ significantly between cytopenic and noncytopenic patients or between those with persistent and new-onset disease. Late infections were more common in patients who were cytopenic at 9 months (38%) and were mostly bacterial (67%).Conclusions: Cytopenia after the completion of therapy is a common complication of frontline FCR that improves over time, particularly for new-onset cases. The presence of persistent cytopenia (lasting up to 9 months after the completion of therapy) should not raise concern about CLL recurrence of the development of TRMM, but should encourage surveillance for bacterial infections for an additional 9 months. [ABSTRACT FROM AUTHOR]

BACKGROUND CD22 expression occurs in >90% of patients with acute lymphocytic leukemia (ALL). Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, is active in ALL. METHODS Patients with refractory-relapsed ALL received treatment with inotuzumab. The first 49 patients received single-dose, intravenous inotuzumab at doses of 1.3 to 1.8 mg/m2 every 3 to 4 weeks. In the next 41 patients, the schedule was modified to inotuzumab weekly at a dose of 0.8 mg/m2 on day 1 and at a dose of 0.5 mg/m2 on days 8 and 15, every 3 to 4 weeks, based on higher in vitro efficacy with more frequent exposure. RESULTS Ninety patients were treated; 68% were in salvage 2 or beyond. Overall, 17 patients (19%) achieved a complete response (CR), 27 (30%) had a CR with no platelet recovery (CRp), and 8 (9%) had a bone marrow CR (no recovery of counts), for an overall response rate of 58%. Response rates were similar for single-dose and weekly dose inotuzumab (57% vs 59%, respectively). The median survival was 6.2 months overall, 5.0 months with the single-dose schedule, and 7.3 months with the weekly dose schedule. The median survival was 9.2 months for patients in salvage 1 (37% at 1 year), 4.3 months for patients in salvage 2, and 6.6 months for patients in salvage 3 or later. The median remission duration was 7 months. Reversible bilirubin elevation, fever, and hypotension were observed less frequently on the weekly dose. In total, 36 of 90 patients (40%) underwent allogeneic stem cell transplantation. Veno-occlusive disease was noted in 6 of 36 patients after stem cell transplantation (17%), was less frequent after the weekly schedule (7%), and with less alkylators in the preparative regimen. CONCLUSIONS Inotuzumab single-agent therapy was highly active, safe, and convenient in patients with refractory-relapsed ALL. A weekly dose schedule appeared to be equally effective and less toxic than a single-dose schedule. Cancer 2013;119:2728-2736. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fluorescence in situ hybridization can detect genomic abnormalities in up to 80% of cases and provides prognostic information on patients with chronic lymphocytic leukemia (CLL). Although 13q deletion as the sole abnormality has been found to confer a favorable prognosis, there are little data as to whether there is a difference in prognostic value between monoallelic versus biallelic deletion of 13q. METHODS: The authors reviewed the electronic database for patients with CLL who carried the 13q deletion as the sole abnormality and presented to The University of Texas MD Anderson Cancer Center (MDACC). Untreated patients were separated into 2 groups: those having monoallelic versus those with biallelic deletion of 13q. Using Mann-Whitney, chi-square, and Kaplan-Meier analysis, the baseline quantitative and qualitative variables for each group, along with the time from presentation to MDACC to treatment, were compared. RESULTS: A total of 176 patients were identified; 143 patients had a monoallelic deletion of 13q, whereas 33 patients had a biallelic deletion. The only significantly different values between the groups were albumin (4.5 g/dL vs 4.4 g/dL; P = .01) and zeta-chain-associated protein kinase 70 (ZAP70) expression (1.7% vs 4.8%; P = .010). The median time from fluorescence in situ hybridization analysis to treatment in both the monoallelic and biallelic groups had not been reached ( P = not significant). CONCLUSIONS: Except for inconsequential differences in albumin and ZAP70 expression, there was no difference in the baseline characteristics between patients with CLL who had monoallelic or biallelic deletion of 13q. In addition, there was no significant difference in endpoints, including time to treatment. Cancer 2012;3531-3537. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The long-term outcome of patients with chronic phase chronic myeloid leukemia treated with imatinib after failure of interferon alpha therapy has not been detailed. METHODS: In total, 368 patients were analyzed. Univariate and multivariate survival analyses were conducted using standard statistical methods. RESULTS: Overall, 247 patients (67%) achieved a complete cytogenetic response (CCyR). Of the 327 patients who were studied, 207 patients (63%) achieved a major molecular response (MMR), and 99 patients (30%) had undetectable breakpoint cluster region/c-abl oncogene (BCR-ABL) levels at some time during therapy. The estimated 10-year survival rate was 68%, the progression-free survival rate was 67%, and the event-free survival rate was 51%. In multivariate analysis, age ≥60 years, hemoglobin <10 g/dL, bone marrow basophils ≥5%, any peripheral blasts, and clonal evolution were independent adverse factors for survival. The estimated 7-year survival rate according to the presence of no factors (n = 154), 1 or 2 factors (n = 190), or ≥3 factors (n = 24) were 93%, 70%, and 25%, respectively ( P < .01). Achieving an MMR, a CCyR, or a partial cytogenetic response at 12 months was associated with significantly better 10-year survival rate in a landmark analysis (10-year survival rate, 80%-90%) compared with achieving a minor cytogenetic response or a complete hematologic response (10-year survival rate, 55%-65%) or another response (10-year survival rate, 10%). In a landmark analysis that included imatinib response at 12 months, achieving a major cytogenetic response or better (hazard ratio, 0.12; P < .001) and achieving a complete hematologic response or a minor cytogenetic response (hazard ratio, 0.36; P = .003) were significant favorable prognostic factors. CONCLUSIONS: The current results indicated that the estimated 10-year survival rate of 68% for patients with chronic myeloid leukemia who receive imatinib after failure on interferon has improved. Cancer 2012;118: 3116-22. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Deletions of derivative chromosome 9 are a poor prognostic factor in patients with chronic myeloid leukemia (CML) treated with hydroxyurea, interferon, or stem cell transplantation. Imatinib may overcome the adverse prognostic impact of deletions of derivative chromosome 9. METHODS: A study was undertaken to investigate the prognostic impact of deletions of derivative chromosome 9 in 353 patients with CML receiving the second generation tyrosine kinase inhibitors (TKIs) nilotinib (n = 161) or dasatinib (n = 192). RESULTS: Deletion of derivative chromosome 9 status was determined in 245 (69%). Twenty-eight (11%) patients, 22 in chronic phase, 4 in accelerated phase, and 2 in blast phase, carried deletions of derivative chromosome 9, including 17 receiving nilotinib and 11 receiving dasatinib ( P = .47). Overall survival (OS) at 24 months was similar between patients with or without deletions of derivative chromosome 9 (70% vs 71%, P = .76). For patients in chronic phase, no significant differences in overall major cytogenetic response (77% vs 82%, P = .57) or complete cytogenetic response (77% vs 81%, P = .71) rates were observed between patients with or without deletions of derivative chromosome 9. At 24 months, patients with CML in chronic phase without deletions of derivative chromosome 9 had improved event-free survival (EFS) (88% vs 66%, P = .07) and OS (96% vs 82%; P = .08) compared with those carrying deletions of derivative chromosome 9. However, multivariate analysis established second-line versus frontline second generation TKI therapy as the only adverse prognostic factor for EFS and increased bone marrow blast burden and older age as independent adverse prognostic factors for OS. CONCLUSIONS: Deletions of derivative chromosome 9 do not appear to be an independent risk factor for survival among patients with CML in chronic phase receiving second generation TKIs. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The role of nonmyeloablative allogeneic stem cell transplantation (NST) in the treatment of chronic lymphocytic leukemia (CLL) is not well established. The authors report on long-term experience with NST in relapsed/refractory CLL and define prognostic factors associated with outcome.Methods: The authors reviewed the outcome of 86 patients with relapsed/relapsed CLL enrolled in sequential NST protocols.Results: The median patient age was 58 years. Patients were heavily pretreated before transplantation, and 43 required immunomanipulation after NST for persistent or recurrent disease. Immunomanipulation included withdrawal of immunosuppression, rituximab, and step-wise donor lymphocyte infusions. Of 43 patients receiving immunomanipulation, 20 (47%) experienced a complete remission. Patients with human leukocyte antigen (HLA) genotype A1(+) /A2(-) /B44(-) were more likely to experience a complete remission (P = .0009), with rates of 9%, 36%, 50%, and 91%, respectively, for 0, 1, 2, and 3 of these HLA factors. This resulted in significant improvement in progression-free-survival rates of 68.2% at 5 years for patients with all 3 HLA factors. Overall, the estimated 5-year survival rate was 51%. In a multivariate model, a CD4 count of <100/mm(3) and a below normal serum immunoglobulin G level at study entry were associated with a short survival duration (P < .0001).Conclusions: These results confirm the potential cure of relapsed/refractory CLL with NST and provide the first evidence that immunoglobulin G and CD4 levels are predictive of overall survival after NST in CLL and that human leukocyte antigen alleles predict response to immunomanipulation. [ABSTRACT FROM AUTHOR]

Background: Management of asymptomatic early stage chronic lymphocytic leukemia (CLL) centered on expectant surveillance for active disease warranting chemotherapy. In CLL, elevated serum β-2 microglobulin (β2M) levels were associated with more rapid disease progression and shorter survival (OS).Methods: An early intervention trial was designed to assess response, time-to-progression (TTP), and OS after immunotherapy with standard-dose rituximab (375 mg/m² intravenously weekly for 8 consecutive weeks) in 34 asymptomatic untreated early stage CLL with β2M level ≥ 2 mg/dL.Results: Long-term follow-up and results are reported. The overall response rate in 34 patients was 82% (9% complete [CR]), median TTP in the 28 responders was 23 months, the median time to subsequent treatment was 43 months, and the 8-year OS rate was 74% (median follow-up, 102 months).Conclusions: Early treatment with rituximab was well tolerated and safe. Further studies are needed to determine if this intervention can decrease CLL-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

BACKGROUND: The authors conducted a phase 1/2 study of tipifarnib in combination with idarubicin and cytarabine (IA) in 95 patients with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome. METHODS: Induction consisted of idarubicin 12 mg/m² a day on days 1-3, cytarabine 1.5 g/m² intravenously continuously daily on days 1-4 (days 1-3 if age ≥60 years), and tipifarnib, with the first cohort (n = 6) receiving 200 mg orally twice a day and all others receiving 300 mg twice a day for 21 days every 28 days. Consolidation consisted of 5 courses of idarubicin 8 mg/m² a day on days 1-2, cytarabine 0.75 g/m² a day on days 1-3, and tipifarnib 300 mg twice a day for 14 days every 4-6 weeks. Maintenance with tipifarnib 300 mg twice a day for 21 days every 4-6 weeks was continued for 6 months. RESULTS: With a median follow-up of 33 months, 61 patients achieved complete remission (CR) (64%), and 9 achieved complete remission with incomplete platelet recovery (CRp) (9%). The median duration of CR was not reached. Median overall survival was 17 months. The most common grade 3 adverse events were gastrointestinal toxicities, liver dysfunction, and skin rash. Compared with historical IA, IA and tipifarnib showed a better CR duration (P = .04) and a trend toward a higher CR rate in patients with chromosome 5/7 abnormalities. CONCLUSIONS: The combination of IA and tipifarnib is safe and active. Further studies exploring different dosages and schedules are warranted, particularly in patients with poor-risk AML. [ABSTRACT FROM AUTHOR]

BACKGROUND: Anemia is a frequent side effect of imatinib in patients with chronic myeloid leukemia (CML). Erythropoietic-stimulating agents have been used for treatment of imatinib-induced anemia. There are no data on long-term safety of erythropoietic-stimulating agents in CML patients. METHODS: The records of chronic phase CML patients who received treatment with imatinib were reviewed for use of erythropoietic-stimulating agents and occurrence of thrombotic events. Data on cytogenetic response and survival were analyzed by use of erythropoietic-stimulating agent. RESULTS: A total of 608 patients were included, and 217 patients received erythropoietic-stimulating agents. There were 30 thrombotic episodes. Patients who received erythropoietic-stimulating agents had a higher rate of thrombosis (8.5% vs 2.6%, P = .0025). There was no difference in cytogenetic response rate and survival by use of erythropoietic-stimulating agent. Development of grade 3-4 anemia occurred in 62 (10%) patients and was associated with significantly worse response and survival in patients in late chronic phase. By multivariate analysis, use of erythropoietic-stimulating agents was not a risk factor for event-free survival. CONCLUSIONS: In our cohort of chronic phase CML patients, use of erythropoietic-stimulating agents did not impact survival or cytogenetic response rate, but was associated with a higher thrombosis rate. Severe anemia is associated with worse survival and response. [ABSTRACT FROM AUTHOR]

BACKGROUND: Most patients with chronic myelogenous leukemia (CML) harbor residual disease, as evidenced by molecular techniques even after treatment with high-dose imatinib (ie, 800 mg/d). Interferon alpha (IFN α) is efficacious in CML likely due to its immunomodulatory properties, and is synergistic in vitro with imatinib and granulocyte macrophage-colony stimulating factor (GM-CSF). METHODS: A study was undertaken to determine whether adding pegylated (PEG) IFN α-2b and GM-CSF to high-dose imatinib may improve the complete molecular response rate in patients with CML in chronic phase. Ninety-four patients were treated with imatinib 800 mg/d for the first 6 months, then randomly assigned to continue high-dose imatinib alone (n = 49) or in combination with PEG IFN α-2b 0.5 µg/ kg/wk and GM-CSF 125 mg/m² 3x weekly (n = 45). RESULTS: The median follow-up for all patients was 54 months (range, 7-70 months). There were no differences in the rates of complete cytogenetic response (87% vs 90%; P = 1.0), or of major (77% vs 77%; P = 1.0) or complete (11% vs 13%; P = 1.0) molecular response (on the international scale) at 12 months between the 2 arms, or at any time during the study. Adverse events led to PEG IFN α-2b discontinuation in all patients. CONCLUSIONS: The addition of PEG IFN α-2b and GM-CSF to high-dose imatinib therapy does not improve significantly the cytogenetic or molecular response rates compared with high-dose imatinib alone. The high dropout rate in the PEG IFN α-2b arm may have compromised its potential immunomodulatory benefit. [ABSTRACT FROM AUTHOR]

BACKGROUND: Imatinib is an effective tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML) in chronic phase (CP). Although some patients may fail on therapy with imatinib, effective salvage therapy is available with second-generation TKIs. Current measurement of efficacy for each therapy is judged by its individual impact on overall survival and event-free survival (EFS). METHODS: In total, 586 patients with CML in CP who received imatinib were included in this analysis in 2 cohorts: imatinib as front-line therapy (n = 281) or after failure on interferon-α (IFN-α) (n = 305). By accounting for successful salvage treatment (ie, regain of complete cytogenetic response), the current EFS (CEFS) rate was calculated to obtain a more accurate impression of the outcome of patients with CML who received treatment with sequential TKIs. RESULTS: For patients who received imatinib after failing on IFN-α, the 7-year EFS rate was 61%, whereas the CEFS rate was 69%. The 7-year EFS rate for patients who received imatinib as initial therapy was 81% compared with a 7-year CEFS rate of 88%. CONCLUSIONS: CEFS provided a more accurate representation of the outcome of patients with CML in CP. These patients may frequently be treated successfully with subsequent TKIs after experiencing failure on the first TKI. [ABSTRACT FROM AUTHOR]

The article presents information on a study which evaluated the efficacy of subcutaneous alemtuzumab to treat residual disease in patients with chronic lymphocytic leukemia (CLL). Information on the incidence of CLL is offered. Study subjects were patients in partial remission (PR), nodular PR (nPR) or complete remission (CR) who had disease in bone marrow confirmed by two-color flow cytometry analysis. A discussion on the findings is detailed. It concludes that self-administered, subcutaneous alemtuzumab was safe and active for residual disease.

The article presents information on a study which characterized clinical parameters and treatment outcomes of 29 patients with therapy-related acute promyelocytic leukemia (t-APL). Background on t-APL is given. Study subjects were randomly assiged to receive either with arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) or with standard ATRA plus anthracycline-based chemotherapy. A discussion on the research findings is detailed.

This article discusses a study which compared two schedules of palonosetron versus ondansetron in the treatment of chemotherapy-induced nausea and vomiting in patients with acute myelogenous leukemia (AML) receiving cytarabine. The study included 47 patients on ondansetron and 48 patients on each of the palonosetron. It revealed that the daily assessments of emesis did not show significant differences between the study arms.

This article discusses a study which defined the prognosis for adult patients with acute lymphocytic leukemia (ALL) after first salvage through multivariate analyses of patient and disease characteristics. The study involved 124 patients who had refractory-recurrent ALL after receiving frontline therapy and 121 patients who were referred. It revealed that 75 of 245 patients achieved complete response (CR), the median CR duration was five months and the median survival was 4.7 months.

The author comments on a study published within the issue which reviewed six studies by the Eastern Cooperative Oncology Group (ECOG) involving patients with acute myeloid leukemia (AML) who achieved a complete response (CR) either following one course or two courses of chemotherapy. The findings of the study are discussed. The author opines that the findings raise significant issues pertaining to frontline AML therapy, such as the prognosis for unselected patients with AML who were given standard frontline AML therapy.

The article examines whether or not anthracycline dose intensification in a modified hyper-cyclophosphamide, vincristine, doxorubicin and dexmethasone (CVAD) regime can improve the results in treating adult acute lymphoblastic leukemia (ALL). A study administered anthracycline-based consolidation chemotherapy on 63 ALL patients with liposomal daunorubicin and cytabarine to the modified regimen which included rituximab. It was found that early anthracycline intensification within the modified regimen did not improve the treatment outcome for ALL patients.

The article discusses a study which determined the incidence, predictors and outcome for acute kidney injury (AKI) in patients with acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS). The study included 537 patients with AML or HR-MDS who are undergoing induction chemotherapy from 1999 to 2007. It identified the independent risk factors for AKI, which include age, mechanical ventilation and the use of vancomycin.