Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens.

The expression of CD56 antigen in acute promyelocytic leukemia (APL) blasts has been associated with short remission duration and extramedullary relapse. We investigated the clinical significance of CD56 expression in a large series of patients with APL treated with all-trans retinoic acid and anthracycline-based regimens. Between 1996 and 2009, 651 APL patients with available data on CD56 expression were included in 3 subsequent trials (PETHEMA LPA96 and LPA99 and PETHEMA/HOVON LPA2005). Seventy-two patients (11%) were CD56(+) (expression of CD56 in ≥ 20% leukemic promyelocytes). CD56(+) APL was significantly associated with high white blood cell counts; low albumin levels; BCR3 isoform; and the coexpression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. For CD56(+) APL, the 5-year relapse rate was 22%, compared with a 10% relapse rate for CD56(-) APL (P = .006). In the multivariate analysis, CD56 expression retained the statistical significance together with the relapse-risk score. CD56(+) APL also showed a greater risk of extramedullary relapse (P < .001). In summary, CD56 expression is associated with the coexpression of immaturity-associated and T-cell antigens and is an independent adverse prognostic factor for relapse in patients with APL treated with all-trans-retinoic acid plus idarubicin-derived regimens. This marker may be considered for implementing risk-adapted therapeutic strategies in APL. The LPA2005 trial is registered at http://www.clinicaltrials.gov as NCT00408278.

Outcome of a Real-Life Population of Patients With Acute Promyelocytic Leukemia Treated According to the PETHEMA Guidelines: The Polish Adult Leukemia Group (PALG) Experience.

BACKGROUND: Acute promyelocytic leukemia (APL) has a favorable prognosis. However, results of randomized studies do not necessarily reflect the outcomes of a real-life population. PATIENTS AND METHODS: We analyzed 283 unselected APL patients treated in 20 Polish hospitals between 2005 and 2017. All patients were intended to be treated with PETHEMA (Programa Español para el Tratamiento de las Hemopatías Malignas) protocols based on all-trans retinoic acid plus chemotherapy. RESULTS: The probability of overall survival at 4 years was 67%, while event-free survival was 64%. The early death (ED) rate was 20.1% (n = 57), while 3.5% (n = 10) patients died before induction therapy was started. The main causes of ED included hemorrhage (45.6%), infections (17.5%), and differentiation syndrome (14.5%). Of 273 treated patients, 214 (78.4%) experienced hematologic morphologic remission, 2 (0.7%) were found to have resistant disease, 47 (17.2%) could not be evaluated for response because of ED, and in 6 (3.7%) no data concerning the response were available. Multivariate analyses showed that predictors of ED and overall survival were Eastern Cooperative Oncology Group performance status > 2, age > 60 years, and all types of bleeding episodes that occurred before starting therapy, while an additional predictor of event-free survival was high white blood cell count (> 10 109/L). CONCLUSION: ED remains a major problem in APL patients, especially in a real-life population. Shortening of the time between the initial contact with a health care professional, and all-trans retinoic acid administration and the use of appropriate supportive care could improve the outcome of unselected APL population, mainly by reducing the ED rate.

An analysis of the impact of CD56 expression in de novo acute promyelocytic leukemia patients treated with upfront all-trans retinoic acid and anthracycline-based regimens.

Out of 956, there were 95 (10%) CD56+ APL patients treated with PETHEMA ATRA and chemotherapy. CD56+ expression was associated with high WBC, BCR3 isoform, and co-expression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. CD56+ vs CD56- APL presented higher induction death rate (16% vs 8%, p = .02) and 5-years cumulative incidence of relapse (33% versus 10%, p = .006), irrespectively of the Sanz score (low-risk 47% versus 5%, p < .001; intermediate 23% versus 7%, p < .001; and high-risk 42% versus 21%, p = .007). In the multivariate analysis, CD56 + (p < .0001), higher relapse-risk score (p = .001), and male gender (p = .05) retained the independent predictive value. CD56+ APL also showed a greater risk of CNS relapse (6% versus 1%, p < .001) and lower 5-year OS (75% versus 83%, p = .003). The AIDA-based LPA2012 trial, with an intensified consolidation schedule for CD56+ APL, will elucidate whether an intensified consolidation schedule could mitigate the relapse rate in this setting.

Clinical significance of complex karyotype at diagnosis in pediatric and adult patients with de novo acute promyelocytic leukemia treated with ATRA and chemotherapy.

Although additional cytogenetic abnormalities (ACA) do not affect the prognosis of patients with t(15;17) acute promyelocytic leukemia (APL), the role of a complex karyotype (CK) is yet to be clarified. We aimed to investigate the relationship of CK with relapse incidence in 1559 consecutive APL patients enrolled in three consecutive trials. Treatment consisted of AIDA induction followed by risk-adapted consolidation. A CK (CK) was defined as the presence of ≥2 ACA, and a very CK (CK+) as ≥3 ACA. Eighty-nine patients (8%) had a CK, of whom 41 (4%) had CK+. The 5-year cumulative incidence of relapse (CIR) in patients with CK was 18%, and 12% in those with <2 ACA (p=.09). Among patients with CK+, the 5-year CIR was 27% vs 12% (p=.003), retaining the statistical significance in multivariate analysis. This study shows an increased risk of relapse among APL patients with CK + treated with ATRA plus chemotherapy front-line regimens.

[Pregnancy outcome in five women after autologous bone marrow transplantation for acute lymphoblastic leukaemia]. / Przebieg ciaz i porodów u kobiet po przebytym zabiegu autotransplantacji szpiku z powodu ostrej bialaczki limfoblastycznej.

There are reports of successful pregnancies in women with haematological malignancies after either autologous or allogeneic bone marrow transplantation (BMT). We report six cases of uncomplicated pregnancies in five women treated with high-dose chemotherapy, radiotherapy and autologous bone marrow transplantation (ABMT) for acute lymphoblastic leukaemia. One patient was diagnosed as having leukaemia during pregnancy. The pregnancy ended with medical termination. Each woman received conditioning regimens without total body irradiation (TBI). Of five women, who received AMBT, all resumed spontaneous cyclical menstruation post transplantation. All of them conceived naturally between 15-52 months following ABMT. We noted one miscarriage in our 29-year-old patient. Six pregnancies went to term and each resulted in the successful delivery of a full-term baby. We did not notice any case of relapse of leukaemia in pregnancy.

[Effectiveness of splenectomy in high-risk patients needing surgery]. / Skutecznosc splenektomii w przypadkach o wysokim ryzyku lub nie rokujacych powodzenia zabiegu.

Splenectomy is a useful method of treatment in some hematological disorders (congenital microspherocytosis, ITP, hypersplenism). However in many clinical situations the unclear prognostic factors, bad patient's condition or non-typical disease's course may impede the decision to splenectomize. We present a history of three successfully splenectomized patients. In each of reported cases the complicated course required detailed disease and treatment analysis. Our results indicate that splenectomy should be considered as a therapeutic option in the thrombocytopenic patients. This group of patients should be immediately referred to specialized centres.

[Outcome assessment of kidney transplantation in Katowice in years 1983-2000]. / Ocena wyników przeszczepiania nerek w osrodku katowickim w latach 1983-2000.

The aim of this study was to analyze the 20 years experience of the Renal Transplantation Center in Katowice in which 681 kidney transplants in 678 patients were performed between March 1983 and December 2000. Several parameters have been analyzed in this group: HLA class I and class II antigens compatibility, the mean cold ischaemia time, time to restore renal function, recipient's mortality, the causes of recipients' death, the early post-transplant complications, and patients' and grafts' survival. In the analyzed period of time HLA matching improved significantly (the median number of matched antigens of class I and II increased from 1 to 3) and the mean cold ischaemia time decreased from 27 to 20 hours. The number of transplants with early graft function increased from 9.5 to 42% and the number of primary non-functioning grafts decreased from 16 to 9%. Also recipients' early mortality declined significantly (from 31 to 5.5%). Among early post-transplant complications cases with sepsis and gastrointestinal bleeding decreased significantly. Improvement of both one-year and five-years graft survival was observed. During the observation period the number of donors did not changed and the rate of living kidney donors remained very low (1.76% of all transplants).

[Causes of chronic renal failure and clinical status of patients during initiation of hemodialysis therapy in upper Silesian region]. / Przyczyny przewleklej niewydolnosci nerek i stan kliniczny chorych w chwili rozpoczecia hemodializoterapii na obszarze Górnego Slaska.

UNLABELLED: The aim of this study was to evaluate the causes of chronic renal failure and clinical status of patients during the onset of hemodialysis therapy in Upper Silesian region. Medical documentation and questionnaires of 175 patients initiating hemodialysis therapy from November 1999 to October 2000 were analyzed. Concentrations of creatinine, calcium, phosphorus in serum, hemoglobin in blood, concomitance of hypertension, frequency of uremic symptoms, HBV and HCV infections, and occurrence of mature arterio-venous fistula before the first hemodialysis were assessed. The main causes of end stage kidney disease were: chronic glomerulonephritis (29%), diabetic nephropathy (27%), polycystic kidney disease (15%), interstitial (11%) and hypertensive (9%) nephropathy. The first contact with nephrologist for 30% of patients was the admission for the initiation of renal replacement therapy. 33% of patients were treated due to chronic renal failure shorter than 1 year. Only 53% of patients had matured arterio-venous fistula during the first hemodialysis session. Anemia, hyperphosphatemia (>1.7 mmol/l) and arterial hypertension were found in 87%, 49.5% and 82% of patients starting hemodialysis therapy, respectively. The main symptoms of chronic uremia were weakness, pruritus, swelling, nausea and insomnia. CONCLUSIONS: Most of patients with chronic renal failure is referred to the nephrologists at the advanced stage of the disease. It is especially true for patients with diabetic nephropathy.

Does plasma leptin concentration predict the nutritional status of hemodialyzed patients with chronic renal failure?

BACKGROUND: Patients with chronic renal failure are characterized by hyperleptinemia, and leptin is presumed to be an anorectogenic hormone. The aim of this prospective study was to analyze changes in body composition and parameters of nutritional status in relation to changes in plasma leptin concentration in uremic patients during the first year of hemodialysis therapy. MATERIAL/METHODS: 21 patients (10 F, 11 M, mean age 51+/- 3 years, BMI 24.3+/-1.1 kg/m2) were enrolled in this study. Nutritional status was evaluated by anthropometric parameters, estimation of body composition (DEXA method), and biochemical markers (plasma concentrations of albumin, cholesterol, triglycerides, transferrin) and plasma leptin concentration. Tests were performed twice: immediately after initiation of hemodialysis therapy and again 12 months later. RESULTS: After 12 months of hemodialysis therapy, the changes in body mass (-2.6+/-0.8 kg; p=0.23), total fat mass (TFM) (-0.3+/-0.8 kg; p=0.68) and total lean mass (TLM) (+0.5+/-0.8 kg; p=0.26) were insignificant. Plasma leptin concentration and estimated biochemical nutritional parameters did not change markedly. A significant positive correlation was noticed between TFM and plasma leptin concentration (R=0.521; p=0.02) at the beginning of hemodialysis therapy and between changes in TFM and plasma leptin concentration (R=0.466; p=0.04) after one year. CONCLUSIONS: Plasma leptin concentration does not predict forthcoming changes in body composition and changes of nutritional status in uremic patients after the first year of hemodialysis.