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[Microangiopathic hemolytic anemia associated with cancers. Symptomatic treatment by plasma exchange].

OBJECTIVE: To determine the interest of plasmapheresis in the management of cancer-associated microangiopathic haemolytic anaemia (MHA) not due to cancer treatment. MATERIAL AND METHODS: [corrected] National retrospective study using the file of the French Hemapheresis Society. RESULTS: We isolated 6 patients (5 men and a woman aged 32 to 69-year-old) who had prostatic (4 cases) or breast carcinomas or Hodgkin's disease. Diagnosis of cancer preceeded MHA in 3 patients (from 2 to 4 years). Bone or bone marrow metastases were demonstrated in 5 patients. The clinical presentation included anuria (4 cases), bleeding (4 cases), and laboratory findings were consistent with microangiopathic haemolysis and thrombopenia in all cases and intravascular coagulation (2 cases) and/or renal failure (4 cases). MHA symptomatic treatment included 4 to 10 courses of plasmapheresis, extra-renal epuration (4 patients), anticoagulation (4 patients) and/or antiagregant (3 cases), haemodialysis (4 cases) and vincristine (2 cases). Cancer treatment consisted of antitumoural chemotherapy (2 cases) and/or hormonotherapy (5 cases). In all cases, haemolysis, thrombopenia and intravascular coagulation were controlled within 30 days. MHA treatment was effective alone in 3 patients. No relapse were observed in 3 patients whereas the course of cancer continued in 2 patients. Two patients relapsed and died from MHA after 4 and 36 months. Two patients relapsed and died from MHA within a few months and 1 was lost to follow-up. CONCLUSION: Symptomatic treatment of cancer-associated MHA including plasmapheresis may be useful while waiting for an aetiologic management of the tumour.

Adenocarcinoma↗

[Extreme thrombocytopenia in sarcoidosis (author's transl)].

A report on a 17-year-old patient with sarcoidosis who was admitted to hospital because of acute generalized tendency to hemorrhage in very severe thrombopenia. This type of thrombopenia has a high primary mortality rate unless steroids are administered in high doses in good time. If the patient survives this crisis, the prognosis for him and the sarcoidosis is good.

Adolescent↗

[Immunoglobulins in Hematology. Immunologic thrombopenic purpura].

Immunologic thrombopenic purpura refers to several diseases including the most frequent, autoimmune thrombopenic purpura (AITP). Immunologic thrombopenia is related to anti-platelet autoantibodies, usually IgGs. In 15 to 20% of the cases, no auto-antibody can be detected. The severity of the cutaneomucosal manifestations is not always correlated with the degree of thrombopenia but only occurs for platelet counts less than 50 x 10(9)/L. The clinical course includes acute episodes of AITP and complete remissions in 80% of the cases in the episodes of AITP and complete remissions in 80% of the cases in the very young child. Inversely, in the adult, treatment of AITP has been highly debated because chronicity is frequent. Two therapeutic approaches, corticotherapy and splenectomy, have been widely used. Corticoids given at a dose of 0.5 to 1 mg/kg/day leads to remission in 15 to 30% of the cases. Splenectomy, a second intention therapy, leads to platelet counts above 100 x 10(9)/L in 60 to 70% of the patients. In 1981, intravenous polyvalent immunoglobulins were first employed for 13 children in a study reported by Imbach et al. The results have been confirmed in children and in adults. There are few side effects with this method and the dose of 1 g/kg over 2 days is effective. Response is rapid (platelet counts above 50 x 10(9)/L in 1 to 5 days) but often temporary (relapse to former levels in 5 to 45 days). The high cost of this intravenous polyvalent immunoglobulins has led to much debate over their use.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Concomitant radiochemotherapy with cisplatin (CDDP), 5-fluorouracil (5-FU) and mitomycin C (MMC) in locally advanced carcinoma of the oropharynx. Results of a phase II trial].

In order to improve loco-regional control in locally advanced oropharyngeal carcinoma, a phase II trial was designed to establish the feasibility of concomitant conventional radiotherapy and three cycles of chemotherapy at day 1, 21 and 42 with cisplatin (CDDP) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 day 1 to day 4, and mitomycin C (MMC) 10 mg/m2 day 1. From March 1990 to September 1993, 27 patients (mean age: 55) were included in this study. Three patients (11%) were T2N0, 19 (70%) T3 (T3N0: n = 9, T3N1: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4N0: n = 1, T4N1: n = 1, T4N2: n = 2, T4N3: n = 1). With a mean follow-up of 34 months (17-59), ten patients (37%) were alive, free of disease; among the 17 other patients, seven died with cancer. Loco-regional control rate was 85%. One and 2-year survival rates were respectively 48 and 31% for overall and disease-free survival; respective corrected overall survival rates were 68 and 61%. Grade 3 or 4 mucositis was 81%; enteral feeding was necessary for 63% of the patients; mean loss of weight was 5.7 kg. Grade > 2 thrombopenia occurred in 11 patients (41%), grade > 2 neutropenia in eight patients (29%) , grade > 2 anemia in four patients (15%). Febrile neutropenia or aplasia occurred in five patients (19%). Two patients (7%) died during treatment of haematological or infectious complications related to the treatment. Another patient died 2 months after treatment with grade 4 thrombopenia and septicemia. Addition of MMC to 5-FU and CDDP might have been partly responsible of this increased toxicity. A high complete response rate has been achieved with this concomitant radio-polychemotherapy, but with a severe digestive and haematological toxicity, which did not allow to conclude to the feasibility of this therapeutic association.

Adult↗

[Indication for spinal anesthesia for cesarean section in HELLP syndrome coagulopathy].

We describe the relation between coagulation and local-regional anesthesia in two women with HELLP syndrome who required emergency cesarean delivery. HELLP syndrome involves hemolysis, elevated liver enzyme levels and thrombopenia complicating the hypertension of pregnancy. Regional anesthesia presents advantages for mother and fetus in this context but also involves the risk of coagulopathy. In the first case we describe, coagulation was normal before surgery and epidural anesthesia was therefore prescribed. The initial epidural puncture was hemorrhagic and a second, higher puncture was made to insert the catheter. Shortly after surgery severe thrombopenia developed and lasted 24 hours; formation of an epidural hematoma caused by vascular lesion during puncture was suspected. The epidural catheter was left in place, and the patient was kept under observation and seen by a neurologist within the first 48 hours. Outcome was good. In the second patient, epidural puncture was contraindicated by the presence of preoperative coagulopathy, and the cesarean was performed without complications under intradural anesthesia provided with low doses of bupivacaine and fentanyl. The coagulopathy that accompanies HELLP syndrome should be assessed not only before taking the decision on anesthetic technique; as the condition can be progressive it can become most severe after the epidural puncture is performed, as shown by the first case we describe. The patient's condition must be watched closely until coagulation becomes normal. Removal of the epidural catheter must wait until coagulopathy is resolved. When coagulopathy is evident before surgery, intradural anesthesia is a safe option provided hemodynamic stability is assured, as demonstrated by the second case we report.

Adult↗

A single dose of thrombopoietin shortly after myelosuppressive total body irradiation prevents pancytopenia in mice by promoting short-term multilineage spleen-repopulating cells at the transient expense of bone marrow-repopulating cells.

Thrombopoietin (TPO) has been used in preclinical myelosuppression models to evaluate the effect on hematopoietic reconstitution. Here we report the importance of dose and dose scheduling for multilineage reconstitution after myelosuppressive total body irradiation (TBI) in mice. After 6 Gy TBI, a dose of 0.3 microgram TPO/mouse (12 microgram/kg) intraperitoneally (IP), 0 to 4 hours after TBI, prevented the severe thrombopenia observed in control mice, and in addition stimulated red and white blood cell regeneration. Time course studies showed a gradual decline in efficacy after an optimum within the first hours after TBI, accompanied by a replacement of the multilineage effects by lineage dominant thrombopoietic stimulation. Pharmacokinetic data showed that IP injection resulted in maximum plasma levels 2 hours after administration. On the basis of the data, we inferred that a substantial level of TPO was required at a critical time interval after TBI to induce multilineage stimulation of residual bone marrow cells. A more precise estimate of the effect of dose and dose timing was provided by intravenous administration of TPO, which showed an optimum immediately after TBI and a sharp decline in efficacy between a dose of 0.1 microgram/mouse (4 microgram/kg; plasma level 60 ng/mL), which was fully effective, and a dose of 0.03 microgram/mouse (1.2 microgram/kg; plasma level 20 ng/mL), which was largely ineffective. This is consistent with a threshold level of TPO required to overcome initial c-mpl-mediated clearance and to reach sufficient plasma levels for a maximum hematopoietic response. In mice exposed to fractionated TBI (3 x 3 Gy, 24 hours apart), IP administration of 0. 3 microgram TPO 2 hours after each fraction completely prevented the severe thrombopenia and anemia that occurred in control mice. Using short-term transplantation assays, ie, colony-forming unit-spleen (CFU-S) day 13 (CFU-S-13) and the more immature cells with marrow repopulating ability (MRA), it could be shown that TPO promoted CFU-S-13 and transiently depleted MRA. The initial depletion of MRA in response to TPO was replenished during long-term reconstitution followed for a period of 3 months. Apart from demonstrating again that MRA cells and CFU-S-13 are separate functional entities, the data thus showed that TPO promotes short-term multilineage repopulating cells at the expense of more immature ancestral cells, thereby preventing pancytopenia. The short time interval available after TBI to exert these effects shows that TPO is able to intervene in mechanisms that result in functional depletion of its multilineage target cells shortly after TBI and emphasizes the requirement of dose scheduling of TPO in keeping with these mechanisms to obtain optimal clinical efficacy.

Animals↗

[Common variable immunodeficiency associated with autoimmune thrombocytopenia: anesthetic management].

A 44-year-old man diagnosed of common variable immunodeficiency associated with thrombopenia due to autoimmunity required anesthesia for anal fissure repair and hemorrhoidectomy. Hemostatic complications developed after surgery, with extreme thrombopenia (1,000 platelets/pl) and analytical changes that necessitated administration of six units of platelets from apheresis, as well as immunoglobulins, antifibrinolytic agents (e-aminocaproic acid) and granulocytic colony stimulating factors. Anesthesia for such patients is reviewed, with emphasis on careful management of the airways, preparation of sufficient material for surgery (rapid transfusion equipment, large caliber intravenous catheters, sterile material) and orientation of anesthetic technique toward general anesthesia through a laryngeal mask.

Adjuvants, Anesthesia↗

Yoshi 864 (NSC 102627) 1-propanol, 3, 3'-iminodi-dimethanesulfonate (ester) hydrochloride: a phase 1 study.

Yoshi 864 was given i.v. push daily times 5 with 6 weeks' followup. Dose escalation was from 0.25 mg/kg to 2.7 mg/kg. Toxicity and effectiveness were first seen at 1.5 mg/kg. Twenty-five courses were given to 16 patients at or above this level. In 16 of 22 courses, exclusive of CML, thrombopenia and/or leukopenia occurred. Mean platelet and WBC nadirs occurred on day 24 and 29 with recovery taking 1-2 weeks and 2-3 weeks respectively. Hb fell in 11 courses. At 2.7 mg/kg, nausea and vomiting lasting 6-12 days occurred in 3 of 7 courses; during 5 coures patients slept 20 hours a day, and 1 was comatose for 2 days. Two patients with squamous cell carcinoma and 1 with an unknown primary responded. Both patients with CML had clinical remissions. It is recommended that a cooperative Phase II Study in a broad spectrum of human solid tumors including lymphomas and chronic myelocytic leukemia be undertaken at a dose level of 2 mg/kg.

Alkylating Agents↗

Dysmyelopoietic syndromes. A search for prognostic factors in 193 patients.

Dysmyelopoietic syndromes cover sideroblastic or nonsideroblastic refractory anemia with or without excess of blasts, subacute or chronic myelomonocytic leukemia. The evolution of 193 patients was studied with regard to the initial hematologic picture. A certain number of variables of prognostic value have then been isolated: excess of marrow blasts (more than 5%); presence of circulating blasts or karyotypic anomalies; reduction in the number of polymorphonuclear leukocytes (less than 1.043 10(9)/l, of monocytes (less than 0.136 10(9)/l), of platelets (less than 140 10(9)/l), of in vitro granulopoietic progenitors (less than 5 per 10(5) nucleated cells plated), of erythrocytic incorporation of 59Fe at day 14 (less than 12%), of hemoglobin level (less than 92 g/l); previous exposure to radiation or chemotherapy; early hemolysis in 51Cr-labeled erythrocytes study; marrow heterogeneity in histology; less than 20% of ringed sideroblasts. The correlation between these variables and adjustments related to the length of survival and the order of magnitude of the critical level of the log-rank test show that the most significant variables in descending order are: excess of marrow blasts, neutropenia, thrombopenia, presence of circulating blasts, the type of erythropoietic insufficiency, and decrease of in vitro growth.

Anemia, Sideroblastic↗

Sequential non-cross-resistant chemotherapy regimens (MOPP and CAVmP) in Hodgkin's disease stage IIIB and IV.

Fifty consecutive patients with advanced Hodgkin's disease were treated in a multicentre study with 6 cycles of an alternating scheme of MOPP and CAVmP followed by irradiation to a dose of 20 Gy. The objective was to increase complete remission (CR) and cure rates by alternating two effective noncross-resistant regimens with subsequent consolidation of the remission by irradiating bulky nodes. A total of 47 patients completed the treatment and are evaluable. In the first 13 patients the irradiation fields amounted to a total or subtotal nodal irradiation with inclusion of the spleen. In case of organ involvement the affected organ was also included in the irradiation field. The irradiation protocol was later changed to an irradiation of the initially involved sites because of severe leucopenia and thrombopenia. After completion of the chemotherapy 32 (68%) patients (for Stage IIIB and IV patients: 63% and 71%, respectively) achieved a CR, after ending the radiotherapy the percentage of CR increased to 87% (for stage IIIB and IV patients: 90% and 86%, respectively). Five of the patients relapsed in an irradiated and nonirradiated area, three patients in a nonirradiated field. The actuarial 3-year survival rate for the entire group was 86% and for patients in CR 94%. The relapse-free survival was 73%. It is concluded that this alternating chemotherapy scheme followed by irradiation is at least equally effective as MOPP treatment in achieving a CR, and is probably superior in terms of survival.

Adolescent↗

A phase III trial comparing prednimustine (LEO 1031) to chlorambucil plus prednisolone in advanced breast cancer.

Prednimustine is an ester of chlorambucil and prednisolone. The drug has had some activity in experimental as well as in human tumors, including breast cancer. The objective of the current study is to compare the clinical effectiveness and toxicity of prednimustine with its components of chlorambucil plus prednisolone, and to compare the clinical effectiveness and toxicity of a continuous treatment with an intermittent one. Two hundred and one patients with advanced breast cancer were randomized to the following treatments: I: prednimustine continuously; 40 mg/m2 d; II: prednimustine intermittently, 160 mg/m2 d 1 to 5, repeated every three weeks; and III: chlorambucil 8 mg/m2 d plus prednisolone 8 mg/m2 d, both given continuously. All treatments were given orally. One hundred and ninety five patients were evaluable for assessment of response to the treatments. The response rates were 21% in both of the prednimustine-treated groups, whereas only 11% of the patients treated with chlorambucil and prednisolone responded. The duration of remission with continuous prednimustine was longer than with the other two treatment groups, but not significantly so. One hundred and ninety five patients were evaluable for assessment of hematologic toxicity. No differences were observed between the two prednimustine-treated groups, whereas the group treated with chlorambucil plus prednisolone experienced a significantly higher degree of leukopenia and/or thrombopenia. Subjective toxicities, nausea, vomiting and psychical symptoms were only moderate in the three treatment groups, but significantly more pronounced in the group treated with intermittent prednimustine. Because of these promising results, prednimustine should be compared to other alkylating agents in patients with advanced breast cancer in randomized trials.

Adult↗

Vinblastine-ifosfamide-cisplatin treatment of bulky seminoma.

Eighteen patients with pure seminoma in advanced Stages IIC-IV of disease were treated with VIP combination chemotherapy consisting of vinblastine (6 mg/m2, days 1 and 2), ifosfamide (1.5 g/m2, days 1 to 5), and cisplatin (20 mg/m2, days 1 to 5). Eleven patients had Stage IIC, four had Stage III, three had Stage IV, and two had primary extragonadal seminoma. Primary histologic diagnoses were typical seminoma in 15 patients and anaplastic seminoma in three patients. Human chorionic gonadotropin (HCG) levels were elevated to 350 U/1 in eight patients; alpha-fetoprotein (AFP) levels were always normal. No primary lymphadenectomy was carried out. Seven of 18 patients had prior radiotherapy and were treated because of relapse or progression. There was one early death and one patient has not yet completed therapy. Of 16 evaluable patients, 14 reached complete remission (CR) (88%), which was documented surgically in six cases, whereas in the non-pretreated group, all nine patients reached CR and in the pretreated group, CR could be induced in five of seven patients (71%). The remission duration ranged from 6+ to 41+ months (median, 29+ months). No relapse has occurred. The bone marrow toxicity of VIP was remarkable. Because of leukopenia below 1000/mm3 and/or thrombopenia below 50,000/mm3, dose reduction and interval prolongation were necessary in 10 of 16 patients, especially in all those who were pretreated. Even though it is not superior to other platin-based regimens, VIP chemotherapy is highly effective in bulky seminoma with and without prior radiotherapy.

Adult↗

Detection of bone marrow relapse in patients with small cell carcinoma of the lung.

From a total of 874 patients with small cell lung cancer (SCC), a series of 104 patients were reviewed to determine if bone marrow relapses are detectable by routine clinical investigations. Autopsy, including microscopical bone marrow examination, was performed in all the 104 patients and bone metastases were disclosed in 36 patients (35%). After retrospective evaluation it was concluded that dose modification, occurrence of leukopenia plus fever, need of blood transfusion, leukopenia, and thrombopenia during treatment all were without predictive value in the detection of bone marrow relapse. Increased concentrations of lactate dehydrogenase and alkaline phosphatase were, however, positively correlated to the finding of bone marrow relapse.

Adult↗

High-dose cisplatin for metastatic soft tissue sarcoma.

Between August 1984 and January 1987, the Southwest Oncology Group (SWOG) registered 46 patients with metastatic sarcomas on SWOG 8465, a Phase II trial of high-dose cisplatin in patients with metastatic soft tissue sarcoma. Six patients were ineligible for the following reasons: poor performance status (two patients); ineligible diagnosis (three patients, two with Ewing's sarcoma of bone and one with metastatic chondrosarcoma); and evaluable but nonmeasurable disease (one patient with bone-only disease). Of the 40 fully evaluable patients, 34 had received prior chemotherapy; treatment was with cisplatin (40 mg/m2/d for 5 consecutive days). Cisplatin was mixed in 250 ml of 3% NaCl and hydrated with a normal saline solution at a rate of 250 ml/h, beginning 12 hours before the first dose of cisplatin was specified. The second treatment was given 3 weeks after the first, with all subsequent treatments given every 4 weeks. After three cycles of treatment, responding patients were treated at a cisplatin dose of 20 mg/m2/d for 5 consecutive days. Leukopenia was of Grade 3 or 4 in seven patients, whereas thrombopenia was of Grade 3 or 4 in eight patients. More severe myelosuppression was produced in patients who had received prior radiotherapy. A single case of reversible Grade 4 nephrotoxicity was produced; neurotoxicity was observed in 11 cases, but was of Grade 3 in only 2 cases. Of the 40 evaluable cases, six showed partial responses or no responses, for a major response rate of 15%. High-dose cisplatin has minor activity and major toxicity in the treatment of metastatic soft tissue sarcomas, and should be considered investigational.

Adult↗

Treatment results and acute and late toxicity of radiation therapy for testicular seminoma.

From 1977 to 1988, 215 patients with a diagnosis of testicular seminoma were referred to the University Hospital, Hamburg, West Germany, for radiation therapy (RT). In 15 patients a careful review of the histologic condition showed signs of embryonal cell carcinoma. Three patients refused completion of therapy. No patient was lost to follow-up. On this basis, a retrospective review of 197 patients was carried out. One hundred thirty-three patients were classified as Stage I (67%), 39 as Stage II (20%), 8 as Stage III (4%), and 17 as Stage IV (9%). One hundred eighty patients had classic seminoma and 17 had anaplastic seminoma. All patients underwent high inguinal orchiectomy before treatment. Seven patients with Stages III and IV received chemotherapy before RT. Patients with Stages I and II were treated with 40-Gy photons to paraaortic and parailiac fields. Ten patients with Stage III and IV seminoma received 30-Gy photons to mediastinal and supraclavicular fields as well. Sixty patients received additional inguinal RT. The overall 5-year survival rate (corrected for intercurrent death, except for treatment toxicity) was 100% for Stage I, 100% for Stage II, 87% for Stage III, and 87% for Stage IV. The mean follow-up time was 6.3 years (range, 0.6 to 11.9 years). An evaluation of all patients showed no difference according to histologic condition or prior chemotherapy. Mediastinal and supraclavicular irradiation showed no improvement in treatment results. Acute toxicity consisted of mild to moderate emesis, increased bowel frequency, erythema, and, in four cases leucopenia and thrombopenia (all World Health Organization [WHO] Grades I to II). However, one patient died of a pulmonary fibrosis 1 month after mediastinal irradiation and 2 months after polychemotherapy, and a gastroduodenal ulcer developed in another patient 1.5 months after paraaortic RT and prior polychemotherapy. Overall, the data suggest that to avoid overtreatment and consecutive treatment morbidity reduced doses of 30 Gy and a restrictive treatment planning adapted to the individual risk are sufficient for RT for testicular seminoma. An alternative to postoperative RT in Stage I (and possibly Stage II) seminoma could be no RT, but close follow-up instead.

Combined Modality Therapy↗

Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases.

One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma.

Adult↗

Myelodysplasia. The clinical spectrum of 51 patients.

BACKGROUND: Over a 15 year period, the authors followed 51 male patients with myelodysplastic syndromes whose clinical findings, laboratory data, and evolution demonstrated a wide spectrum of disease. METHODS: The following characteristics were assessed: age at diagnosis, risk factors, clinical presentation, laboratory features, category of myelodysplasia, leukemic conversion, and overall survival. RESULTS: The clinical manifestations included hemolytic episodes in two patients, antibody-mediated thrombopenia in one, marked marrow fibrosis in two; thrombocytosis in three, and simultaneous lymphoproliferative disorders in two. There were 21 patients whose marrow was either normo- or hypocellular. Six patients presented with single cytopenia but not anemia. There were six instances of overlapping of the French-American-British classification. Eighteen patients progressed to acute leukemia and 1 to chronic myelomonocytic leukemia. CONCLUSIONS: These observations indicate that patients with myelodysplastic syndromes may have single cytopenia without anemia that progresses to acute leukemia and may, rarely, evolve into chronic myelomonocytic leukemia. The clinical aspects of these syndromes may include autoimmune phenomena and myeloproliferative features.

Adult↗

B-cell chronic lymphocytic leukaemia: prognostic value of the immunophenotype and the clinico-haematological features.

Sixty-two previously untreated patients with B-cell chronic lymphocytic leukaemia were analysed to study the prognostic value of both the immunologic phenotype and the clinicobiologic characteristics. Univariate studies showed that none of the immunological markers analysed, sheep-rosette, mouse-rosette, slg, and HLA/DR, CD20, FMC7, CD5, and CD9 antigens, had a significant influence on survival. On the other hand, several clinical and haematological characteristics were identified as being associated with survival: 1) clinical features--presence of lymphadenopathies (P less than .05) and hepatomegaly and/or splenomegaly (P less than .04); 2) haematologic parameters--presence of anaemia and/or thrombopenia (P less than .05), the absolute peripheral blood lymphocyte count (P less than .03), and the presence of hypogammaglobulinemia (P less than .08); 3) biochemical parameters--serum uric acid (P less than .03); and 4) bone marrow histopathological features--biopsy pattern (P less than .04) and the percentage of lymphocytes in bone marrow aspirate (P less than .03). Both the Rai staging and the International Workshop on CLL staging systems were effective in identifying groups of patients with significantly different prognoses (P less than .05). Multivariate regression analysis demonstrated that the combination of three clinicopathologic characteristics (bone marrow histopathologic pattern, absolute peripheral blood lymphocyte count, and the presence or not of hypogammaglobulinaemia) had the strongest predictive relationship with survival time. In summary, our findings show that the clinicobiological and anatomopathologic parameters have much more prognostic relevance than the immunological markers analysed in the present study.

Antigens, Differentiation↗