AIM To evaluate the importance of the CD34+CD38-cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia ...characteristics and known prognostic factors, as well as with response to therapy and survival.METHODS Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia(AML) were studied between September 2008 and December 2010 at our Institution(Hematology Department, Lyon, France). The CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach using 8 C panels and FACS CANTO and Diva software(BD Bioscience).RESULTS We analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at diagnosis, and investigated the prognostic value of the most immature CD34+CD38-population. Using a cut-off value of 1% of CD34+CD38-from total “bulk leukemic cells” we found that a high(> 1%) level of CD34+CD38-blasts at diagnosis was correlated with advanced age, adverse cytogenetics as well as with a lower rate of complete response after induction and shorter disease-free survival. In a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells and the standardized cytogenetic and molecular risk subgroups, a percentage of CD34+CD38-leukemic cells > 1% was an independent predictor of DFS HR = 2.8(1.02-7.73), P = 0.04 and OS HR = 2.65(1.09-6.43), P = 0.03.CONCLUSION Taken together, these results show that a CD34/CD38 “backbone” for leukemic cell analysis by multicolour flowcytometry at diagnosis provides useful prognostic information.
Prognostic factors for response and survival in higher-risk myelodysplastic syndrome patients treated with azacitidine (AZA) remain largely unknown. Two hundred eighty-two consecutive high or ...intermediate-2 risk myelodysplastic syndrome patients received AZA in a compassionate, patient-named program. Diagnosis was RA/RARS/RCMD in 4%, RAEB-1 in 20%, RAEB-2 in 54%, and RAEB-t (AML with 21%-30% marrow blasts) in 22%. Cytogenetic risk was good in 31%, intermediate in 17%, and poor in 47%. Patients received AZA for a median of 6 cycles (1-52). Previous low-dose cytosine arabinoside treatment (P = .009), bone marrow blasts > 15% (P = .004), and abnormal karyotype (P = .03) independently predicted lower response rates. Complex karyotype predicted shorter responses (P = .0003). Performance status ≥ 2, intermediate- and poor-risk cytogenetics, presence of circulating blasts, and red blood cell transfusion dependency ≥ 4 units/8 weeks (all P < 10−4) independently predicted poorer overall survival (OS). A prognostic score based on those factors discriminated 3 risk groups with median OS not reached, 15.0 and 6.1 months, respectively (P < 10−4). This prognostic score was validated in an independent set of patients receiving AZA in the AZA-001 trial (P = .003). Achievement of hematological improvement in patients who did not obtain complete or partial remission was associated with improved OS (P < 10−4). In conclusion, routine tests can identify subgroups of patients with distinct prognosis with AZA treatment.
Les patients âgés peuvent être traités par des séances d’aphérèse Hequet, Olivier; Revesz, Daniela; Chelghoum, Youcef ...
Transfusion clinique et biologique : journal de la Société française de transfusion sanguine,
September 2019, 2019-09-00, Letnik:
26, Številka:
3
Journal Article
Recenzirano
L’augmentation de l’espérance de vie implique une prise en charge thérapeutique de plus en plus intensive chez les patients âgés. Dans notre service d’aphérèse polyvalent nous avons analysé ...rétrospectivement les indications, l’utilisation de produits sanguins de substitution et la tolérance des séances d’aphérèse réalisées chez des patients âgés, c’est à dire d’au moins 80 ans. En 15 ans, 33 patients âgés ont été traités par aphérèse. L’échange plasmatique (EP) (technique de flux continu par centrifugation) constitue la principale méthode utilisée (n=29, 80–92 ans). La plupart des patients (n=22) a été traitée par quelques séances d’EP (1–4) pour une complication aiguë (hyperviscosité myélome, Waldenström, Guillain Barré ou myasthénie aiguë). Chez le sujet âgé, compte tenu du risque hémorragique par reconstitution lente de facteurs de coagulation lors de séances répétées sur une courte période, du plasma frais congelé (PFC) a été utilisé dans 62 % des séances. Parmi les 7 patients traités de manière chronique (80–88 ans), des PFC n’ont été utilisés que lors de séances réalisées 2 fois par semaine. Toutes ces séances d’EP et la perfusion de PFC ont été bien tolérées. Quatre patients âgés (80-88 ans) ont été traités par photophérèse (lymphomeT de Sezary) dont 2 depuis plus de 4 ans. La plupart des séances (70 %) a été réalisée par technique de flux continu avec une bonne tolérance clinique. Au total, les séances d’aphérèse sont faisables chez les patients âgés, à condition de tenir compte de leurs particularités physiologiques, en prévenant les déséquilibres volémiques (technique en flux continu) et métaboliques (fabrication plus lente des facteurs de coagulation).
AIM: To evaluate quantitatively and qualitatively the different CD34+cell subsets after priming by chemotherapy granulocyte colony-stimulating factor(± G-CSF)in patients with acute myeloid ...leukemia.METHODS: Peripheral blood and bone marrow sampleswere harvested in 8 acute myeloid leukemia patients during and after induction chemotherapy. The CD34/CD38 cell profile was analyzed by multi-parameter flow cytometry. Adhesion profile was made using CXC chemokine receptor 4(CXCR4)(CD184), VLA-4(CD49d/CD29) and CD47.RESULTS: Chemotherapy ± G-CSF mobilized immature cells(CD34+CD38 population), while the more mature cells(CD34+CD38lowand CD34+CD38+populations) decreased progressively after treatment. Circulating CD34+cells tended to be more sensitive to chemotherapy after priming with G-CSF. CD34+cell mobilization was correlated with a gradual increase in CXCR4 and CD47expression, suggesting a role in cell protection and the capacity of homing back to the marrow.CONCLUSION: Chemotherapy ± G-CSF mobilizes into the circulation CD34+bone marrow cells, of which, the immature CD34+CD38-cell population. Further manipulations of these interactions may be a means with which to control the trafficking of leukemia stem cells to improve patients’ outcomes.
It has been proposed that Vitamin D has a significant influence on disease progression in malignancy. This study aims to investigate whether serum levels of 25-hydroxyvitamin D 25(OH)D are associated ...with prognosis in patients with hematological malignancies. This study is based on 105 patients with hematological disease (acute and chronic leukemias, myelodysplastic syndromes, monoclonal gammapathies, and chronic lymphoid disorders), seen over a 6-months period. 25(OH)D deficiency (<20 ng/ml) appeared very common and an inverse relationship was observed between 25(OH)D levels and the response to therapy: lower levels being related to poorer response. In acute leukemias, a significant difference was noted between patients with long-term disease-free survival in those tested at diagnosis (P = 0·001) or in those tested at the time of relapse (P = 0·05). Similarly in patients with Philadelphia-positive leukemias, there was a correlation between molecular response and levels of 25(OH)D (P = 0·01). Previously identified factors, such as age, season, gender, or nutritional index, were not related to circulating 25(OH)D levels. Lower levels of circulating 25(OH)D appeared related to a progressive stage of the disease and poor response to therapy, and, therefore, to the aggressiveness of the disease. It is a potential marker of prognosis in patients with leukemia.
Échanges érythrocytaires chez les enfants de faible poids Hequet, Olivier; Gauthier, Alexandra; Revesz, Daniela ...
Transfusion clinique et biologique : journal de la Société française de transfusion sanguine,
September 2019, 2019-09-00, Letnik:
26, Številka:
3
Journal Article
Recenzirano
Les Échanges Érythrocytaires (EE) sont utilisés pour traiter et prévenir les complications vasculaires graves des patients drépanocytaires. Cependant, le faible poids des jeunes enfants nécessite des ...précautions et une adaptation pour éviter une mauvaise tolérance clinique lors de ces séances. En effet, le volume extracorporel peut représenter un pourcentage non négligeable du volume sanguin de l’enfant lors des EE. Nous avons analysé la tolérance clinique lors des séances d’EE en pédiatrie en adaptant nos pratiques au poids de l’enfant et avons mis en évidence les périodes critiques lors de ces échanges. Chez les enfants de poids inférieur à 20kg (n=5), un amorçage du kit avec un concentré de globules rouges et une perfusion continue d’albumine 4 % (10mL/kg) permettent d’éviter une diminution significative de la tension artérielle (TA) au début et pendant toute la durée de l’EE (25 séances analysées). Chez les enfants pesant entre 20 et 40kg (n=17), la perfusion d’une macromolécule ou d’albumine 4 % (15mL/kg) lors de l’EE permet d’éviter une diminution de la TA uniquement si elle est réalisée de manière strictement continue (217 séances analysées). L’existence d’une anémie (hématocrite inférieur à 23 %) nécessite une perfusion initiale (de volume variable selon le poids de l’enfant) par albumine et une surveillance clinique particulière. De plus, l’échange d’une quantité trop importante de globules rouges prédispose à la survenue de malaises et de baisse de TA chez l’enfant. Au total, la réalisation d’EE est possible chez les enfants de faible poids (>10kg) sans conséquence clinique délétère, à condition de prévoir une stratégie thérapeutique et une surveillance adaptées.
To assess the value of administering timed-sequential chemotherapy (TSC; 2 therapeutic sequences separated by a 4-day interval-free chemotherapy) or high-dose cytarabine (HDAraC) cycles in ...consolidation therapy for acute myeloid leukemia (AML), 459 patients 15 to 50 years of age were enrolled in the prospective randomized Acute Leukemia French Association–9802 trial. Complete remission was achieved in 89%. A total of 237 patients were then randomized to either TSC consolidation (120 patients) or HDAraC consolidation cycles (117 patients). Overall, there was no significant difference between the 2 consolidation arms (5-year event-free survival EFS: 41% for HDAraC vs 35% for TSC), or cumulative incidence of relapse, or treatment-related mortality. Cytogenetically normal AML NPM1+ or CEBPA+ and FLT3-ITD− had the same outcome as those with favorable cytogenetics. When considering favorable and unfavorable risk groups, the trend was in favor of HDAraC. However, the difference became significant when considering intermediate cytogenetics (5-year EFS: 49% vs 29%; P = .02), especially cytogenetically normal AML (5-year EFS: 48% vs 31%; P = .04), which was related to lower relapse rate and less toxicity. This study demonstrates that TSC did not produce any benefit when used as consolidation therapy in younger adults compared with HDAraC. This trial was registered at www.clinicaltrials.gov as #NCT00880243.
Acute leukemia (AL) requiring cytotoxic treatment occurring during pregnancy poses a very difficult therapeutic dilemma.
By means of a mail questionnaire, information on a series of 37 patients with ...a diagnosis of AL during pregnancy was collected from 13 French centers between December, 1988 and November, 2003.
Thirty-one patients had acute myeloid leukemia (AML), and 6 patients had acute lymphoblastic leukemia (ALL). Nine patients were diagnosed during the first trimester, 10 patients were diagnosed during the second trimester, and 18 patients were diagnosed during the third trimester. Fifteen pregnancies ended with therapeutic or spontaneous abortion. There were 13 normal deliveries, including 1 gemellary pregnancy, and 9 Cesarean sections. Twenty-three healthy babies survived from the 37 pregnancies, of whom 15 babies had been exposed to chemotherapeutic agents. A complete remission was achieved in 34 patients. Eleven women had severe extrahematologic complications during the induction remission course. The median disease-free survival (DFS) was not reached, with a 5-year DFS of 54%. Ten patients developed recurrent disease. Overall, 12 of 37 pregnant women died from leukemia.
Pregnancy does not affect the course of AL. In the first trimester, termination of pregnancy should be discussed because of the potential fetal consequences of chemotherapy. Chemotherapy treatment during the second or third trimester may not require termination of pregnancy, because as remission of AL and delivery of a normal infant are likely to be obtained.
Recent cohort and case-control studies have suggested that cigarette smoking may be involved in the etiology of leukemia. Rising trends have been observed for all leukemias when the amount of ...cigarettes smoked increased. However, the magnitude of the trend was strongest for myeloid leukemia. Although no detailed biological mechanism has been proposed, a causal link is made plausible by evidence of systemic effects of cigarette smoke and the presence in cigarette smoke of chemicals (benzene) and radioactive substances that have been associated with leukemia risk. Cigarette smoking has a deleterious effect on survival in leukemia by shortening complete remission duration and subsequent survival. The data reported in this review are derived from the medical literature and from the experience of the authors.
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