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Background: It is unknown whether patients with nonleukemic myeloid sarcoma (MS) and those with acute myeloid leukemia (AML) have similar responses to anti-AML treatment. In the current study, the authors addressed this question by matching MS patients with analogous AML patients and comparing their clinical outcomes.Methods: Twenty-three consecutive patients with MS and 1720 consecutive patients with AML were identified who presented at The University of Texas M. D. Anderson Cancer Center from 1990 to 2004. All AML patients and 16 MS patients received cytarabine plus idarubicin or fludarabine as induction remission therapy. Treated MS patients and AML patients were matched according to cytogenetics, age, Zubrod performance status, and time of treatment. Event-free survival (EFS) and overall survival (OS) were compared using Kaplan-Meier analyses.Results: Complete response rates were 69% in patients with MS and 57% in patients with AML (P = .45). The respective 2-year EFS and OS rates were 32% and 18% (P = .08) and 43% and 29% (P = .11). Matches were identified for 14 MS patients who were paired repeatedly with 91 AML patients to produce 94 matches (3 AML patients were matched twice). EFS was longer in 56 MS pair mates, shorter in 26 pair mates, and similar in 12 pair mates (P = .01; Fisher exact test). OS analyses yielded similar results.Conclusions: Anti-AML therapy was highly effective in patients with nonleukemic MS. The results from this study emphasize the need to treat patients who have nonleukemic MS with AML-type therapy. [ABSTRACT FROM AUTHOR]

Background: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia., Methods: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower. The induction chemotherapy regimen used was mini-hyper-CVD (a lower intensity version of the conventional hyper-CVAD). Odd-numbered cycles (1,3, 5, and 7) comprised intravenous cyclophosphamide (150 mg/m 2 every 12 h on days 1-3) and oral or intravenous dexamethasone (20 mg per day on days 1-4 and days 11-14); no anthracycline was administered. Intravenous vincristine (2 mg flat dose) was given on days 1 and 8. Even-numbered cycles comprised intravenous methotrexate (250 mg/m 2 on day 1) and intravenous cytarabine (0·5 g/m 2 given every 12 h on days 2 and 3). Intravenous inotuzumab ozogamicin was given on day 3 of the first four cycles at the dose of 1·3-1·8 mg/m 2 at cycle 1, followed by 1·0 -1·3 mg/m 2 in subsequent cycles. Maintenance therapy with dose-reduced POMP (purinethol [6-mercaptopurine], oncovin [vincristine sulfate], methotrexate, and prednisone) was given for 3 years. The primary endpoint of this study was progression-free survival at 2 years. Analyses were by intention to treat. The study is ongoing, recruiting patients for an approved expansion phase with a modified treatment plan by protocol amendment. The trial is registered with ClinicalTrials.gov, number NCT01371630., Findings: Between Nov 12, 2011, and April 22, 2017, 52 patients with a median age of 68 years (IQR 64-72) were enrolled. With a median follow-up of 29 months (IQR 13-48), 2-year progression-free survival was 59% (95% CI 43-72). The most frequent grade 3-4 adverse events were prolonged thrombocytopenia (42 [81%] patients), infections during induction (27 [52%]) and consolidation chemotherapy (36 [69%]), hyperglycaemia (28 [54%]), hypokalaemia (16 [31%]), increased aminotransferases (ten [19%]), hyperbilirubinaemia (nine [17%]), and haemorrhage (seven [15%]). Veno-occlusive disease occurred in four (8%) patients. Six (12%) patients died from adverse events that were deemed treatment related (five [10%] from sepsis and one [2%] from veno-occlusive disease)., Interpretation: Inotuzumab ozogamicin plus mini-hyper-CVD chemotherapy is a safe and active first-line therapy option in older patients with newly diagnosed acute lymphoblastic leukaemia and could represent a new therapy for this population. Randomised, phase 3 trials to evaluate the efficacy of this combination compared with the current standard of care in this setting, combination chemotherapy without inotuzumab ozogamicin, are warranted., Funding: MD Anderson Cancer Center., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: The clinical course for patients with chronic lymphocytic leukemia (CLL) is diverse; some patients have indolent disease, never needing treatment, whereas others have aggressive disease requiring early treatment. We continue to use criteria for active disease to initiate therapy. Multivariable analysis was performed to identify prognostic factors independently associated with time to first treatment for patients with CLL., Patients and Methods: Traditional laboratory, clinical prognostic, and newer prognostic factors such as fluorescent in situ hybridization (FISH), IGHV mutation status, and ZAP-70 expression evaluated at first patient visit to MD Anderson Cancer Center were correlated by multivariable analysis with time to first treatment. This multivariable model was used to develop a nomogram-a weighted tool to calculate 2- and 4-year probability of treatment and estimate median time to first treatment., Results: There were 930 previously untreated patients who had traditional and new prognostic factors evaluated; they did not have active CLL requiring initiation of treatment within 3 months of first visit and were observed for time to first treatment. The following were independently associated with shorter time to first treatment: three involved lymph node sites, increased size of cervical lymph nodes, presence of 17p deletion or 11q deletion by FISH, increased serum lactate dehydrogenase, and unmutated IGHV mutation status., Conclusion: We developed a multivariable model that incorporates traditional and newer prognostic factors to identify patients at high risk for progression to treatment. This model may be useful to identify patients for early interventional trials.

Zeta-associated protein-70 (ZAP70) expression measured by flow cytometry has been proposed as a surrogate marker of the somatic mutation status of the immunoglobulin heavy chain variable region (IGHV) genes in chronic lymphocytic leukemia. However, attempts to implement this approach in clinical flow cytometry laboratories have been problematic; many commercially available antibodies give unreliable results. Assessment of ZAP70 protein expression by immunohistochemistry in chronic lymphocytic leukemia tissue sections is an easy, alternative approach, although lack of quantitation and subjective interpretation of results are potential pitfalls. In this study, we correlated ZAP70 protein expression, assessed by immunohistochemistry, with ZAP70 messenger RNA (mRNA) transcript expression, assessed by semi-quantitative real-time reverse transcriptase-polymerase chain reaction assay, with the somatic mutation status of the IGHV genes in previously untreated patients with chronic lymphocytic leukemia. Expression of ZAP70 protein and mRNA transcripts correlated strongly (P=8.238 × 10(-12)). Expression of ZAP70 protein and mRNA transcripts also correlated strongly with the somatic mutation status of the IGHV genes (P=0.000071 and P=0.00076, respectively). Further, ZAP70 positivity by immunohistochemistry was associated with an increased risk of progression to therapy requirement (3-year risk 83% vs 31% for ZAP70 negative by immunohistochemistry, P=0.03). These results show that ZAP70 expression assessed by immunohistochemistry is a reliable surrogate marker of the somatic mutation status of the IGHV genes, and predicts time to progression.

Background: Hodgkin transformation is a rare complication of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In this study, the authors assessed the incidence, presenting characteristics, and outcomes of patients with CLL/SLL who developed Hodgkin lymphoma (HL)., Methods: An electronic database search of patients with CLL/SLL who presented at The University of Texas M. D. Anderson Cancer Center Department of Leukemia between 1975 and 2005 was performed., Results: Among 4121 patients with CLL/SLL, 18 patients (0.4%) developed HL. Presenting features included B-symptoms (67%), lymph node enlargement (79%), splenomegaly (43%), hepatomegaly (29%), hypercalcemia (6%), infection (6%), and mental status changes (6%). The median age was 72 years (range, 49-81 years), and there was a male preponderance (78%). The median time from CLL to HL diagnosis was 4.6 years (range, 0-12.9 years). Fourteen patients (78%) had been previously treated for CLL/SLL. Ten patients (56%) had received >1 prior therapy. The median beta2-microglobulin level was 4.5 mg/L, and the median lactate dehydrogenase level was 610 IU/L. Epstein-Barr virus (EBV) was positive by in situ hybridization for EBV-encoded RNA in 3 of 4 tested patients. Fourteen patients (78%) received chemotherapy. The overall response rate was 44% (complete response rate, 19%). The median overall survival duration was 0.8 years (range, 0.03 years-6.7+ years). The median failure-free survival (FFS) duration was 0.4 years., Conclusions: The rates of response, survival, and FFS in patients with Hodgkin transformation of CLL/SLL were inferior to those reported in patients with de novo HL and were similar to those in patients with Richter syndrome., ((c) 2006 American Cancer Society.)