An international phase 2 study combining cladribine and cytarabine (Ara-C) was initiated for patients with refractory, risk-organ–positive Langerhans cell histiocytosis (LCH) in 2005. The protocol, ...comprising at least two 5-day courses of Ara-C (1 g/m2 per day) plus cladribine (9 mg/m2 per day) followed by maintenance therapy, was administered to 27 patients (median age at diagnosis, 0.7 years; median follow-up, 5.3 years). At inclusion, all patients were refractory after at least 1 course of vinblastine (VBL) plus corticosteroid, all had liver and spleen involvement, and 25 patients had hematologic cytopenia. After 2 courses, disease status was nonactive (n = 2), better (n = 23), or stable (n = 2), with an overall response rate of 92%. Median disease activity scores decreased from 12 at the start of therapy to 3 after 2 courses (P < .0001). During maintenance therapy, 4 patients experienced reactivation in risk organs. There were 4 deaths; 2 were related to therapy toxicity and 2 were related to reactivation. All patients experienced severe toxicity, with World Health Organization grade 4 hematologic toxicity and 6 documented severe infections. The overall 5-year survival rate was 85% (95% confidence interval, 65.2%-94.2%). Thus, the combination of cladribine/Ara-C is effective therapy for refractory multisystem LCH but is associated with high toxicity.
•Patients with LCH, risk organs, refractory to standard VBL-steroid regimen have a poor survival, ∼30%.•In a phase 2 study, with 5 years' median follow-up, cladribine and Ara-C was shown to improve the survival up to 85% for this group.
We analyzed prognostic factors of response, response duration, and possible impact on survival of epoetin α, epoetin β, or darbepoetin α (DAR) with or without granulocyte colony-stimulating factor in ...403 myelodysplastic syndrome (MDS) patients. Sixty-two percent (40% major and 22% minor) and 50% erythroid responses were seen, and median response duration was 20 and 24 months according to IWG 2000 and 2006 criteria, respectively. Significantly higher response rates were observed with less than 10% blasts, low and int-1 International Prognostic Scoring System (IPSS), red blood cell transfusion independence, serum EPO level less than 200 IU/L, and, with IWG 2006 criteria only, shorter interval between diagnosis and treatment. Significantly longer response duration was associated with major response (IWG 2000 criteria), IPSS low to INT-1, blasts less than 5%, and absence of multilineage dysplasia. Minor responses according to IWG 2000 were reclassified as “nonresponders” or “responders” according to IWG 2006 criteria. However, among those IWG 2000 minor responders, response duration did not differ between IWG 2006 responders and nonresponders. Multivariate adjusted comparisons of survival between our cohort and the untreated MDS cohort used to design IPSS showed similar rate of progression to acute myeloid leukemia in both cohorts, but significantly better overall survival in our cohort, suggesting that epoetin or DAR treatment may have a favorable survival impact in MDS.
In order to standardize cellular hematology practices, the French-speaking Cellular Hematology Group (Groupe Francophone d’Hématologie Cellulaire, GFHC) focused on Perls’ stain. A national survey was ...carried out, leading to the proposal of recommendations on insoluble iron detection and quantification in bone marrow. The criteria presented here met with a “strong professional agreement” and follow the suggestions of the World Health Organization’s classification of hematological malignancies.
The phosphoinositide 3-kinase (PI3K/Akt) pathway is activated in acute myelogenous leukemia (AML) and is promising for targeted inhibition. Ninety-two patients with primary AML were analyzed for ...PI3K/Akt constitutive activation. Fifty percent of the patients presented with constitutive PI3K activation (PI3K +). No difference was observed between PI3K + and PI3K − groups concerning age, sex, white blood cell count, lactate dehydrogenase (LDH) level, bone marrow blast cells, French-American-British (FAB) classification, cytogenetics, RAS or nucleophosmin (NPM) mutations. Slightly more FLT3-ITD was detected in the PI3K − group (P = .048). The complete remission rate was similar between the 2 groups. With a median follow-up of 26 months, we observed for PI3K + and PI3K − patients, respectively, 56% and 33% overall survival (P = .001) and 72% and 41% relapse-free survival (P = .001). Constitutive PI3K/Akt activity is a favorable prognosis factor in AML, even after adjustment for FLT3-ITD, and may confer a particular sensitivity to chemotherapy. A better understanding of the downstream effectors of the PI3K/Akt pathway is needed before targeting in AML.
The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway has been shown to be frequently activated in blast cells from patients with acute myeloid leukemia (AML) and to contribute to survival and ...proliferation of these cells. Of the 8 distinct mammalian isoforms of PI3K, it is the class I PI3Ks (p110α, p110β, p110γ, and p110δ) that are responsible for Akt activation. It is not known which PI3K isoform is critical in AML. Here we show that the p110δ isoform of PI3K is consistently expressed at a high level in blast cells from AML, in contrast to the other class I isoforms, the expression of which was very variable among patients. IC87114, a p110δ-selective inhibitor, suppressed both constitutive and Flt-3–stimulated Akt activation in blasts to the same extent as Ly294002, an inhibitor of all PI3K isoforms. Moreover, IC87114 inhibited AML cell proliferation without affecting the proliferation of normal hematopoietic progenitor cells. These observations identify p110δ as a potential therapeutic target in AML.
According to WHO recommendations, diagnosis of chronic myelomonocytic leukemia (CMML) beforehand requires microscopic examination of peripheral blood to identify dysplasia and/or blasts when ...monocytes are greater or equal to 1.0 × 10
9
/L and 10% of leucocytes. We analyzed parameters derived from Sysmex
TM
XN analyzers to improve the management of microscopic examination for monocytosis. We analyzed results of the complete blood count and the positioning and dispersion parameters of polymorphonuclear neutrophils and monocytes in 61 patients presenting with CMML and 635 control patients presenting with a reactive monocytosis. We used logistic regression and multivariate analysis to define a score for smear review. Three parameters were selected: neutrophil/monocyte ratio, structural neutrophil dispersion (Ne-WX) and monocyte absolute value. We established an equation in which the threshold of 0.160 guided microscopic examination in the search for CMML abnormalities with a sensitivity of 0.967 and a specificity of 0.978 in the learning cohort (696 samples) and 0.923 and 0.936 in the validation cohort (1809 samples) respectively. We created a score for microscopic smear examination of patients presenting with a monocytosis greater or equal to 1.0 × 10
9
/L and 10% of leucocytes, improving efficiency in laboratory routine practice.
Purpose
We aimed at investigating whether early metabolic response to corticosteroid therapy may be used as a diagnostic tool to discriminate between cancer and sarcoidosis, a well-known cause of ...false-positive 2-deoxy-2-F-18fluoro-
d
-glucose-positron emission tomography (FDG-PET) findings in oncology.
Procedure
Two cancer patients with biopsy-proven sarcoidosis or sarcoid-like reaction had multiple thoracic FDG foci. After infectious disease had been excluded, patients received oral corticosteroids for 16 and 14 days, respectively, and underwent posttherapeutic FDG-PET examination.
Results
Posttreatment PET revealed a complete metabolic response in both patients, and clinical and imaging follow-up showed no sign of cancer progression.
Conclusion
Early metabolic response to systemic corticosteroid treatment may be used as a tool in the establishment of final diagnosis when sarcoidosis is suspected in a cancer patient and could be capable of differentiating cancer from sarcoidosis in the case of coexisting diseases.
In order to standardize cellular hematology practices, the French-speaking Cellular Hematology Group (Groupe Francophone d’Hématologie Cellulaire, GFHC) focused on Perls’ stain. A national survey was ...carried out, leading to the proposal of recommendations on insoluble iron detection and quantification in bone marrow. The criteria presented here met with a “strong professional agreement” and follow the suggestions of the World Health Organization’s classification of hematological malignancies.
According to WHO recommendations, diagnosis of chronic myelomonocytic leukemia (CMML) beforehand requires microscopic examination of peripheral blood to identify dysplasia and/or blasts when ...monocytes are greater or equal to 1.0 × 10
/L and 10% of leucocytes. We analyzed parameters derived from Sysmex
XN analyzers to improve the management of microscopic examination for monocytosis. We analyzed results of the complete blood count and the positioning and dispersion parameters of polymorphonuclear neutrophils and monocytes in 61 patients presenting with CMML and 635 control patients presenting with a reactive monocytosis. We used logistic regression and multivariate analysis to define a score for smear review. Three parameters were selected: neutrophil/monocyte ratio, structural neutrophil dispersion (Ne-WX) and monocyte absolute value. We established an equation in which the threshold of 0.160 guided microscopic examination in the search for CMML abnormalities with a sensitivity of 0.967 and a specificity of 0.978 in the learning cohort (696 samples) and 0.923 and 0.936 in the validation cohort (1809 samples) respectively. We created a score for microscopic smear examination of patients presenting with a monocytosis greater or equal to 1.0 × 10
/L and 10% of leucocytes, improving efficiency in laboratory routine practice.
The prognostic value of fluorodeoxyglucose positron emission tomography (FDG-PET) and gallium-67 scan (GS) performed early after chemotherapy was assessed in 40 patients with newly diagnosed ...aggressive lymphoma. FDG-PET and GS were performed before and after three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or two cycles of ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone), with or without rituximab. Thirty-five patients had diffuse large B-cell lymphoma (DLBCL), two had mantle-cell lymphoma and three had T-cell lymphoma. Four patients relapsed despite early negative FDG-PET and GS including all three patients with T-cell lymphoma. Nine patients stayed in remission despite positive FDG-PET and or GS of whom five showed moderate intensity residual bone uptake. Seven of these nine early false positives had a negative exam at the end of treatment. In patients with DLBCL, the 2-year event-free survival was 85% for negative versus 30% for positive FDG-PET patients (P = 0.003) whereas it was 78% for negative versus 33% for positive GS patients (P = 0.018). Sensitivity, specificity and diagnostic accuracy of FDG-PET and GS were not significantly different: 90% versus 70%, 76 versus 80% and 80 versus 77%, respectively. We conclude that both FDG-PET and GS are valuable tools to early predict outcome in patients with DLBCL.
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![Early 2′-Deoxy-2′-[18F]Fluo...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1536-1632/small "Early 2′-Deoxy-2′-[18F]Fluoro-d-Glucose PET Metabolic Response after Corticosteroid Therapy to Differentiate Cancer from Sarcoidosis and Sarcoid-like Lesions")
