Prognostic discrimination among younger patients with chronic granulocytic leukemia: relevance to bone marrow transplantation

To obtain information relevant to the question of bone marrow transplantation, we examined the prognostic significance of disease features recorded at the time of diagnosis among 625 patients, aged 5 to 45, with Philadelphia chromosome-positive, nonblastic chronic granulocytic leukemia. The actuarial death rate for this population was 5% during the first year after diagnosis, 12% during the second year, and averaged 22.5% per year during the next eight years. Multivariable regression analysis of features recorded in nearly all cases indicated that sex, spleen size, hematocrit, platelet count, and percentage of circulating blasts were significant prognostic indicators. Analyses of additional data available in 113 to 421 cases suggested that serum lactic dehydrogenase activity, percentage of blasts in marrow, nucleated RBCs in blood, and percentage of basophils plus eosinophils might also provide useful prognostic information. A Cox model, generated with five variables representing features recorded regularly (the first five listed), permitted segregation of these patients into three groups with significantly different survival patterns. The high-risk group exhibited an actuarial mortality of 30% during the first two years after diagnosis and an annual risk of 30% thereafter. In contrast, the most favorable group had a two-year actuarial mortality of 9% and an average risk thereafter of 17% per year, with a median survival of 5 1/2 years. We conclude that it should be possible to classify potential candidates for bone marrow transplantation according to risk with conventional therapy. Such information may be useful in making decisions regarding early v deferred marrow transplantation.     

Multivariate analysis of prognostic factors influencing survival in chronic myelogenous leukemia

Prognostic significance of disease features obtained at the time of initial diagnosis was analyzed in 90 patients with chronic myelogenous leukemia (CML) in chronic phase. Median survival of this population was 45.9 months. Univariate analysis revealed that splenomegaly, bone marrow basophils, bone marrow blasts, peripheral blood blasts, and bone marrow eosinophils were significant prognostic factors for survival, and that peripheral blood leukocytes counts, hemoglobin concentration, performance status, age and lymphadenopathy were factors with border line significance. There were multiple interrelationship among these disease features. Multivariate regression analysis identified that age, hemoglobin concentration, and bone marrow blasts were independent primarily significant prognostic factors for survival. The Cox model generated with three variables of age, hemoglobin concentration, and percent blasts in bone marrow provided a useful representation of risk status in the population. A hazard function derived from the patients population segregated patients into three groups with significantly different survival patterns: A lower risk group, an intermediate group and a high risk group of patients with median survival of 57.8, 49.8 and 38.4 months respectively. Survival after CML blast crisis was short and overall median survival of 54 patients with CML blast crisis was 6.4 months. A sole prognostic factor for survival in blast crisis identified by multivariate analysis was blast cell type at CML blast crisis and patients with lymphoid phenotype had a good prognosis with median survival of 9.8 months. Median survival of myeloid crisis was 4.2 months. No other disease features were identified as significant prognostic factors in the present patient population.     

Prognostic factors in idiopathic myelofibrosis: a simple scoring system with prognostic significance

In a prognostic univariate analysis of a series of 80 patients with idiopathic myelofibrosis the Hb-concentration, the platelet count and osteomyelosclerosis emerged as factors with prognostic significance. A Hb-concentration less than 10 g/dl was associated with a significantly shorter survival than a Hb-concentration greater than or equal to 10 g/dl. A platelet count less than 100 x 10(9)/l also implied a significantly shorter survival. Patients with osteomyelosclerosis on X-ray of the skeleton had a significantly better prognosis as compared to those without osteomyelosclerosis. In a multivariate regression analysis the Hb-concentration consistently emerged as an important prognostic parameter, whereas the platelet count was only of prognostic significance within the first 6 months from diagnosis and the presence of osteomyelosclerosis emerged as a favourable parameter at 3 and 5 years. Based upon the above parameters and spleen size, a prognostic scoring system was designed which categorized the patients into three prognostic groups with highly different survival times (low risk group = 69 months; intermediate risk group = 33 months; high risk group = 4 months).     

Age and platelet count are IPSS‐independent prognostic factors in young patients with primary myelofibrosis and complement IPSS in predicting very long or very short survival

Objectives: The current study was designed to identify International Prognostic Scoring System (IPSS)‐independent prognostic factors in young patients with primary myelofibrosis (PMF). The study also examined the overall risk profile of long‐term (>15 yr) and short‐term (<5 yr) survivors. Methods: Study patients were selected from the Mayo Clinic database for PMF, and study eligibility included age <60 yr, minimum follow‐up of 5 yr and availability of IPSS‐relevant variables at time of diagnosis. Results: A total of 148 consecutive patients met the above‐stipulated criteria. To date, 89 (60%) patients have died; 48 (32%) died within 5 yr of their diagnosis (short‐term survivors). Median follow‐up of patients who are alive was 9 yr (range 5–28) with a >15‐yr survival documented in 16 patients (long‐term survivors). Multivariable analysis identified unfavorable IPSS category (intermediate‐2/high risk), age >50 yr and platelet count <100 × 10⁹/L as independent predictors of inferior survival (P < 0.01). Median survival in the absence of all three risk factors was approximately 18 yr and was shortened to 7 and 1.6 yr in the presence of 1 or ≥2 risk factors, respectively (P < 0.01). Among long‐term survivors, 69% were age ≤50 yr, 100% had favorable IPSS profile and 100% displayed platelet count ≥100 × 10⁹/L; the corresponding figures for short‐term survivors were 29%, 50% and 65% (P < 0.01). Conclusions: Age and platelet count are IPSS‐independent predictors of survival in young patients with PMF, and they complement the IPSS in identifying patients with very long or very short survival.     

Karyotype complements the International Prognostic Scoring System for primary myelofibrosis

Objectives: The International Prognostic Scoring System (IPSS) for primary myelofibrosis (PMF) is based on five independent predictors of inferior survival: age >65 yr, hemoglobin <10 g/dL, leukocyte count >25 × 10⁹/L, circulating blasts ≥1%, and presence of constitutional symptoms. The presence of 0, 1, 2, and ≥3 adverse factors defines low, intermediate‐1, intermediate‐2, and high risk disease, respectively. We examined the additional prognostic relevance of karyotype. Methods: World Health Organization criteria were used for PMF diagnosis. Only patients with bone marrow cytogenetic studies at the time or within 1 yr of diagnosis and a minimum of 20 evaluable metaphases were considered. Cytogenetic findings were categorized as ‘normal’ vs. ‘abnormal’ or ‘favorable’ (normal or with sole abnormalities of 13q? or 20q?) vs. ‘unfavorable’ (all other abnormalities). Results: A total of 109 patients were studied (median age 63 yr). Numbers of patients in the above‐listed four IPSS risk groups were 26, 31, 28, and 24, respectively. Cytogenetic results were abnormal in 33% of the patients and unfavorable in 21%. At a median follow‐up of 35 months, 45 (41%) deaths were recorded. ‘Unfavorable’ (P = 0.008) but not ‘abnormal’ (P = 0.19) karyotype predicted shortened survival and its significance remained on multivariable analysis that included the IPSS or other prognostic tools as covariates. JAK2V617F, detected in 63 (58%) patients, was inconsequential to survival. Conclusions: In PMF, specific cytogenetic abnormalities and not the mere presence of an abnormal karyotype provide important prognostic information that is not accounted for by the IPSS or other established risk factors.     

Clinicopathologic features and prognostic indicators in Chinese patients with myelofibrosis

Objective: To define the clinicopathologic features, outcome, and prognostic indicators of myelofibrosis (MF) in Asian patients.

Methods: Two hundred and seventy consecutive Chinese patients (primary MF, n?=?207; post-polycythemia vera MF, n?=?27; and post-essential thrombocythemia MF, n?=?36) from seven regional referral hospitals were analyzed.

Results: The median overall survival (OS) for primary MF was 66 months. Multivariate analysis showed that age >65 years (P?=?0.02), platelet count?<100?×?10⁹/l (P?=?0.001), and leukemic transformation (P?=?0.001) negatively impacted on OS. The median OS of 63 patients with secondary MF was 44 months. In primary MF, the 10-year cumulative risk of leukemic transformation was 28%. On multivariate analysis, unfavorable karyotypes significantly predicted inferior leukemia-free survival (LFS) (P?=?0.03). In secondary MF, the 10-year cumulative risk of leukemic transformation was 31%. Circulating blasts ≥1% significantly predicted inferior LFS (P?=?0.04). The international prognostic scoring system (IPSS) and dynamic IPSS were not significant survival predictors in our cohort. Eighteen patients underwent allogeneic hematopoietic stem cell transplantation. The median OS post-transplantation was merely 19 months.

Discussion: Platelet count?<100?×?10⁹/l, unfavorable karyotypes, and circulating blasts >1% were negative prognostic indicators.

Conclusion: Chinese MF patients were similar to Western patients in clinicopathologic features and outcome.     

Platelet mass has prognostic value in patients with myelodysplastic syndromes

Platelet mass (mean platelet volume x platelet count) can be derived from data obtained from the routine full blood count and separates patients with myelodysplastic syndromes (MDS) at diagnosis into three distinct prognostic groups: low platelet mass group - median survival 5 months and 5-year survival 0%; intermediate platelet mass group - median survival 30 months and 5-year survival 34%; high platelet mass group median survival - not reached at 82 months follow-up with a 5-year survival of 82%. These data provide a simple rapid prognostic index at the time of diagnosis in MDS.     

Long-term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma

We assessed the results of treatment in 283 patients with lung or bone metastases from differentiated thyroid carcinoma who were followed for up to 40 yr (median, 44 months) after the discovery of the metastases. The survival rates from the time of discovery of the metastases were 53% at 5 yr, 38% at 10 yr, and 30% at 15 yr; 156 patients died. Multivariate analysis revealed that only 4 variables had an independent prognostic significance for survival. They were extensive metastases, older age at discovery of the metastases, absence of radioiodine uptake by the metastases, and moderately differentiated follicular cell type. The site of metastases (lung or bone) was not a prognostic factor for survival after treatment of metastatic disease. Remission was achieved in 79 patients after metastases were found. The only predictive factor for 5-yr disease-free survival after treatment of metastases was the initial extent of disease. Our results suggest that the aim of management should be to detect and treat metastases in patients with thyroid cancer as early as possible.     

Polycythemia vera. A clinical study of 141 patients

Summary The clinical course of 141 unselected patients (64 m, 77 f, median age 59) with polycythemia vera (PV), treated during the period 1967 to 1986 was analyzed to study prognostic factors and the correlation between treatment strategies and complication rates. Therapy was performed according to a prospectively defined treatment protocol. Primary control of the disease was achieved by phlebotomy. Marrow suppression by radioactive phosphorus or low dose busulphan was used only as a second-line therapy or to lower high platelet counts. The clinical course of the patients was characterized by a low rate of acute leukemia (4%) and a high rate of thromboembolic complications (40%). Myelofibrosis developed in 17 patients (12%). Median survival of the patients was 9.4 years. The prognostic influence of several parameters at the time of diagnosis was tested: age, sex, spleen size, percentage of blood blasts + promyelocytes, leucocyte count, platelet count, hemoglobin, hematocrit, reticulocyte count and the values of the lactatdehydrogenase (LDH) and the alkaline neutrophil phosphatase (ANP) all had no significant influence on the length of survival. The prognosis of PV patients with atypical disease presentation at diagnosis was not different from patients with typical disease.     

Improved outcome in adult acute myeloid leukemia is almost entirely restricted to young patients and associated with stem cell transplantation

Prognostic factors were studied in a series of 318 patients with acute myeloid leukemia (AML), 17-90 yr old, treated at a single centre during 1982-98, and representing 79% of the total number of cases registered in the area during this period. Risk group stratification based on cytogenetics, occurrence of antecedent hematological disorder, and leukocyte count could be performed in 93%. Five percent were allocated to the favourable risk group, 40% to standard risk, and 55% to adverse risk. Complete remission (CR) was attained in 52%. The CR rate was higher in the favourable (80%) and standard risk groups (69%) than in the adverse risk group (37%). The CR rate increased from 44% in the 1980s to 60% in the 1990s. The 5-yr survival rate for all patients was only 12%. Low age, promyelocytic leukaemia, treatment in the 1990s, high induction treatment intensity, and non-adverse risk group were favourably associated with survival. The median survival time increased from 115 to 349 d between the 1980s and the 1990s, but the 5-yr survival rate was only 11% for patients over 55 yr of age even in the last decade. For the younger patients, the 5-yr overall survival rate increased from 9% to 35% in the last decade. The median time in first remission was 365 d. Age below 56 yr, allogeneic and autologous transplants, and non-adverse risk group were associated with prolonged response duration. The duration of response among all patients increased from 250 d in the 1980s to 451 d in the 1990s, but event-free survival time did not improve significantly in patients above 55 yr of age. Among patients below 56 yr of age, overall survival and event-free survival were significantly better for those who received allogeneic or autologous transplants in first remission than for those who were treated with chemotherapy only. Overall survival times did not improve from the 1980s to the 1990s among those patients below 56 yr who were treated with chemotherapy only in first remission, in spite of the use of transplants in second remission.     

应用COX模型判断慢性粒细胞白血病患者的预后

应用国际慢性粒细胞白血病(CML)预后研究协作组建立的Cox模型对35例CML患者进行了回顾性分析,高危患者占80％,3年生存率35.7％,中危患者占20％,生存期均超过3年,无1例低危组,提示该模型在我国也有一定的实用价值。在判断CML预后的几个危险因素中,脾脏大小是最重要的,红细胞压积对46岁以下患者预后影响也较大。外周血中原始细胞百分数及血小板计数在高中危组之间差异并不显著。     

Prognostic variables and clinical staging in multiple myeloma

To evaluate the most important factors in the prognosis and staging of multiple myeloma (MM), the presenting clinical features of 163 previously untreated patients with MM were correlated with survival duration using univariate and multivariate regression analyses. The univariate proportional hazard analysis ranked the parameters in the following order of importance: platelet count, hemoglobin level (Hb), tumor cell mass stage, lytic bone lesions, creatinine, and age. When the individual contribution of each variable was assessed by multivariate regression analysis, platelet count was confirmed to be the dominant feature for prognosis and clinical stage provided additional information. The introduction of platelet count could then be used to improve the reliability of the Durie and Salmon staging, by allowing to separate the high-risk group (stages II and III) into a smaller subgroup (22%) of thrombocytopenic patients (less than 150 x 10(9) platelets/L) whose risk of death was actually very high (median survival, 9 months) and a larger subgroup (46%) of patients with normal platelet count and intermediate or standard risk (median survival, 48 months). This simple change in the prognostic system gave rise to markedly different survival curves also after the exclusion of patients with renal failure and applied successfully to both old and young patients (greater than and less than 50 years, respectively). Finally, platelet count, Hb, and lytic bone lesions could be combined simply to stratify patients with normal renal function into three risk groups: (1) low (39% of cases; median survival, 79 months), (2) intermediate (53% of cases; median survival, 48 months), and (3) high (8% of cases; median survival, 19 months).     

Circulating myeloid colony-forming cells predict survival in myelodysplastic syndromes

The growth characteristics and the prognostic value of cytokine-stimulated myeloid colony formation from peripheral blood mononuclear cells (PBMC) of patients with myelodysplastic syndromes (MDS) are largely unknown. In this study we have determined the number of myeloid colony-forming units (mCFUs) in semisolid medium from 112 MDS patients and correlated them with French-American-British (FAB) type, the international prognostic scoring system (IPSS), karyotype, peripheral blood (PB) and bone marrow (BM) blast cells, cytopenias, lactate dehydrogenase (LDH), and survival data. Concerning the FAB classification, lower median mCFUs were found in patients with refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) compared to refractory anemia with excess of blast cells (RAEB) and refractory anemia with excess of blasts cells in transformation (RAEB-T). In vitro growth in MDS clearly correlated with the cytogenetic risk groups defined by the IPSS (30.5/10(5) PBMCs with favorable karyotypes, 191 in the intermediate prognostic group, 677 with unfavorable cytogenetics, p=0.015 favorable vs unfavorable). BM blast cells >5% (60.5 vs 255 colonies, p=0.032) as well as LDH levels above the normal limit (64.5 vs 425 colonies, p=0.045) were also associated with higher colony formation. Patients were stratified according to the number of circulating mCFUs into a low growth, intermediate growth and high growth group. Median survival was 343 days in the high growth, 1119 days in the low growth, and 2341 days in the intermediate growth group ( p=0.0002). Multivariate analyses revealed colony growth ( p=0.0056), PB blast cells ( p=0.0069), cytogenetic risk group ( p=0.024), and platelet count ( p=0.018) to predict survival in our patients. After inclusion of the IPSS risk categories, mCFU levels remained a highly predictive parameter for survival ( p=0.0056) and acute myeloblastic leukemia (AML) transformation ( p=0.0003).     

Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system [see comments]

We studied the survival of 195 patients with agnogenic myeloid metaplasia (AMM) diagnosed between 1962 and 1992 in an attempt to stratify patients into risk groups. Median survival was 42 months. Adverse prognostic factors for survival were age > 60 years, hepatomegaly, weight loss, low hemoglobin level (Hb), low or very high leukocyte count (WBC), high percentage of circulating blasts, male sex, and low platelet count. A new scoring system based on two adverse prognostic factors, namely Hb < 10 g/dL and WBC < 4 or > 30 x 10(3)/L, was able to separate patients in three groups with low (0 factor), intermediate (1 factor), and high (2 factors) risks, associated with a median survival of 93, 26, and 13 months, respectively. An abnormal karyotype (32 cases of 94 tested patients) was associated with a short survival, especially in the low-risk group (median survival of 50 v 112 months in patients with normal karyotype). The prognostic factors for acute conversion were WBC > 30 x 10(3)/L and abnormal karyotype. Thus, hemoglobin level and leukocyte count provide a simple prognostic model for survival in AMM, and the adverse prognostic value of abnormal karyotype may be related to a higher rate of acute conversion.     

An effective therapy for both undifferentiated (including Burkitt''s) lymphomas and lymphoblastic lymphomas in children and young adults

We have used a single intensive chemotherapy regimen in the treatment of young patients with diffuse, aggressive, malignant lymphomas. There were two major histologic types of lymphoma in our series: lymphoblastic lymphomas, which presented most often with mediastinal tumor (64%), and undifferentiated lymphomas (mostly Burkitt's lymphomas), which occurred predominantly in the abdomen (86%). Our objective was to examine the determinants of prognosis in a uniformly treated patient group that included 31 children (2-16 yr) and 34 young adults 17-35 yr). Patients with extensive bone marrow involvement (greater than 50% replacement by tumor cells) were included in the study. Treatment consisted essentially of a 4-drug combination (cytoxan, adriamycin, vincristine, and prednisone) alternating with a 42-hr methotrexate infusion, followed by leukovorin rescue, and included intrathecal prophylactic therapy against central nervous system (CNS) disease. Patients with localized or resected undifferentiated lymphoma received 6 therapy cycles; all other patients received 15 cycles. Radiation therapy was used only in exceptional circumstances. Fifty-eight of 65 patients (89%) achieved complete remission: 97% of children and 82% of adults. The estimated 3-yr survival was 60% (SE 6.4%) with a median follow-up of 3 yr. Analysis of factors associated with remission duration and survival indicated that bone marrow involvement at referral and extensive disease were poor prognostic variables. Patients with lymphoblastic lymphomas and patients with completely resected undifferentiated lymphomas had the best prognosis (81% +/- 12% and 94% +/- 6% estimated 3-yr survival, respectively). Patients with extensive intraabdominal undifferentiated lymphoma (stage D) had the worst prognosis (33% +/- 11% estimated 3 yr survival), but even in this subgroup, bone marrow involvement was an adverse factor (estimated survival in stage D patients with and without bone marrow involvement was 14% +/- 13% and 43% +/- 15%, respectively). Elevated uric acid and/or lactic dehydrogenase (LDH) were also of prognostic significance, but predominantly reflected state, i.e., extent of disease. Age did not significantly influence prognosis. In the undifferentiated lymphoma subgroup, histology (i.e., Burkitt's lymphoma versus non-Burkitt's lymphoma) was not of prognostic significance. Total white count was below 1,000/cu mm in 39% of cycles, and fever associated with granulocytopenia occurred in 17% of cycles. Stomatitis of moderate to severe extent occurred in 50% of cycles.(ABSTRACT TRUNCATED AT 400 WORDS)     

Long-term outcomes for unselected patients with acute myeloid leukemia categorized according to the World Health Organization classification: a single-center experience

The actual utility of a new classification system of acute myeloid leukemia (AML) recently introduced by the World Health Organization (WHO) has not been thoroughly investigated yet. In this study, we evaluated long-term outcomes of unselected AML patients categorized according to the new WHO classification. Between 1990 and 2002, 109 adult AML cases were referred to our hospital. For the entire population, the median survival duration was 1.2 yr with a 5-yr survival rate of 31%. AML with recurrent genetic abnormalities accounted for 26%, AML with multilineage dysplasia for 29%, therapy-related AML for 13%, and AML not otherwise categorized for 32% of classifiable cases. Among the four groups, a significant difference was observed in terms of overall survival (P < 0.0001). Univariate analysis showed that six variables affected survival: cytogenetic risk, age, multilineage dysplasia, prior chemo/radiotherapy, type of treatment (intensive or palliative), and transplantation. However, in multivariate analysis no adverse prognostic impact of multilineage dysplasia and prior chemo/radiotherapy was detected (P = 0.4979 and 0.8702), whereas cytogenetic risk and patient age maintained their prognostic value (P = 0.0005 and 0.0100). These results indicate that outcomes for AML patients appear to be distinguished on the basis of the WHO classification, but the prognostic significance of multilineage dysplasia and prior therapy is lost after adjusting for cytogenetic risk and age. Our findings suggest that the WHO classification may be strengthened by greater emphasis on genetic/cytogenetic information.     

Incidence, clinical features and outcome of essential thrombocythaemia in a well defined geographical area

In an attempt to characterise the clinical features, incidence and outcome of essential thrombocythaemia (ET) we report our experience in a large unselected series of patients from a well defined region. All new cases of ET in the County of Copenhagen were registered during the period 1977-98. We identified 96 cases of ET, yielding an age- and sex-adjusted annual incidence rate of 0.59/100.000 and a point-prevalence at last follow up of 11/100.000. The overall incidence rate was 0.31 and 1.00 per 100.000 population during the consecutive periods 1977-89 and 1990-98, respectively, corresponding to a 3.2-fold increase. Median age at diagnosis was 67 yr (females 68 yr, males 66 yr, range 18-87 yr), and the female to male (F/M) ratio was 2.6:1. At diagnosis, 52% of the patients displayed no ET-related symptoms and were discovered fortuitously by a routine platelet count. Forty-eight percent presented with thrombohaemorrhagic phenomena, of which microvascular disturbances of the central nervous system (CNS), extremities and skin were most frequently observed (23%). Compared to patients diagnosed after 1989, patients diagnosed before 1990 had a significantly higher mean platelet count, white blood cell (WBC) count, lactate dehydrogenase (LDH) value and alkaline phosphatase value. With a median follow up of 70 months, 5-yr survival was 76%, significantly lower than the expected survival of an age- and sex-matched control group (p = 0.0052). Thirty-seven patients experienced a total of 55 thrombohaemorrhagic events during follow-up, corresponding to an incidence of thrombosis and microvascular disturbances or haemorrhage of 8.1% per pt-yr and 2.5% per pt-yr, respectively. The number of patients experiencing thrombosis or microvascular disturbances was significantly higher among the 29 patients who never received acetylsalicylic acid (ASA) compared to the 67 patients who received ASA during follow up (45% vs. 21%; p = 0.017). This study provides population-based data suggesting the benefit of treatment with low-dose ASA in a non-selected population of patients with ET.     

Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients.

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy characterized by wide heterogeneity of clinical presentation and course. CMML shares myelodysplastic characteristics with features of myeloproliferative disorders. No treatment has proven effective in modifying the natural course of the disease. To improve the prognostic assessment of clinical outcome, the associations of patient and disease characteristics with survival times of 213 patients with CMML was investigated retrospectively. Median survival was 12 months. Univariate analysis identified low hemoglobin level; low platelet count; high white blood cell, monocyte, and lymphocyte counts; presence of circulating immature myeloid cells, high percentage of marrow blasts, low percentage of marrow erythroid cells, abnormal cytogenetics, and high levels of serum lactate dehydrogenase and beta(2)-microglobulin as characteristics associated with shorter survival. Hemoglobin level below 120 g/L (12 g/dL), presence of circulating immature myeloid cells, absolute lymphocyte count above 2.5 x 10(9)/L, and marrow blasts 10% or more were independently associated with shorter survival by multivariate analysis and were used to generate a prognostic score. The model identified 4 subgroups of patients with median survival of 24, 15, 8, and 5 months for low, intermediate-1, intermediate-2, and high risk, respectively. Researchers could not confer objective evidence suggesting that arbitrary divisions of CMML by white blood cell counts into "dysplastic" and "proliferative" categories reflect clinical entities differing in the risk of acute leukemia development, although a trend of shorter survival in patients with leukocytosis was observed. The prognostic model was compared with 6 previously published scoring systems for myelodysplastic syndrome/CMML. The reported results should provide an improved assessment of prognosis in CMML.     

Risk factors and a prognostic model for postsplenectomy survival in myelofibrosis

Palliative treatment in myelofibrosis (MF) includes transfusion support, JAK2 inhibitors, involved field radiotherapy and splenectomy. To assist in selecting patients who are likely to benefit from splenectomy, we looked into risk factors for postsplenectomy survival, in 120 consecutive cases (median age 66 years); at the time of splenectomy, 61% displayed red cell transfusion need, 49% platelet count <100 × 10(9)/L, 25% leukocyte count >25 × 10(9)/L, 60% constitutional symptoms and 13% circulating blasts ≥5%; dynamic international prognostic scoring system risk categories were 21% high, 55% intermediate‐2, 21% intermediate‐1 and 3% low. Among informative cases, karyotype was abnormal in 60% and driver mutational status was JAK2 75%, CALR 15%, MPL 4% and triple‐negative 6%. At median follow‐up of 1.3 years, from time of splenectomy, 95 (79%) deaths and 30 (25%) leukemic transformations were recorded. Median postsplenectomy survival was 1.5 years; in multivariable analysis, survival was adversely affected by age >65 years, transfusion need, leukocyte count >25 × 10(9)/L and circulating blasts ≥5%; these variables were subsequently used to devise an HR‐weighted scoring system with high (3‐4 risk factors), intermediate (2 risk factors) and low (0‐1 risk factors) risk categories; the corresponding postsplenectomy median survivals were 0.3 (HR 5.9, 95% CI 3.2‐11.0), 1.3 (HR 2.9, 95% CI 1.8‐4.6) and 2.9 years. Postsplenectomy survival was not affected by driver mutational status or occurrence of leukemic transformation. Leukemia‐free survival was predicted by very high risk karyotype. The observations from the current study might help identify appropriate candidates for splenectomy in MF.     

Staging of chronic lymphocytic leukemia

One-hundred and eighty-eight patients with chronic lymphocytic leukemia were analyzed for prognosis based on Rai's staging system. It was found that stages I and II were not homogeneous as to prognosis. Stage II patients presenting with isolated splenomegaly had a long survival and were pooled with stage 0 patients (low risk group, 30% of cases, relative death rate 0.24, median survival greater than 10 yr). Stages I and II patients with a lymphocyte count higher than 40 x 10(9)/liter had a short survival and were pooled with stages III and IV patients (high risk group, 39% of cases, relative death rate 1.91, median survival 3.3 yr). Stages I and II patients with a lymphocyte count lower than 40 x 10(9)/liter made up an intermediate or standard risk group (31% of cases, relative death rate 1.00, median survival 6.2 yr). This modified staging system applied successfully to both old and young patients (more and less than 60 yr old, respectively).