JAK2<Superscript>V617F</Superscript> positive early stage myeloproliferative disease (essential thrombocythemia) as the cause of portal vein thrombosis in two middle-aged women: therapeutic implications in view of the literature

The present study describes portal vein thrombosis (PVT) in two women as the first and single presenting symptom of latent or masked myeloproliferative disease (MPD). Essential thrombocythemia (ET) was suspected by a sustained increase in platelet count (>400 × 10⁹/l) and slight splenomegaly on echogram. ET could be diagnosed by the presence of large platelet in peripheral blood smear, an increase in clustered large megakaryocytes in bone marrow smear and the presence of the JAK2^V617F mutation. A subsequent biopsy specimen was consistent with the diagnosis of true ET. In patients with a first episode of splanchnic vein thrombosis (SVT), analysis of any venous thrombophilic risk factors as well as a JAK2^V617F mutation status indicative for MPD is warranted. Administration of heparin followed by oral anticoagulation with vitamin K antagonists is the treatment of choice in patients with SVT. Anticoagulation therapy combined with low-dose aspirin and proper treatment of the MPD is recommended in patients with SVT associated with the JAK2^V617F mutation.     

Budd-Chiari syndrome and portal vein thrombosis associated with myeloproliferative disorders: diagnosis and management

The improvement observed in the prognosis of Budd-Chiari syndrome (BCS) since 1985 may be related to a better identification of underlying prothrombotic states. In a recent investigation of the currently identified prothrombotic disorders, one or several prothrombotic disorders were evidenced in 72% of patients with portal vein thrombosis (PVT) and 87% of patients with hepatic vein thrombosis. According to the different criteria used for their diagnosis, myeloproliferative disorders (MPDs) were reported in 25 to 65% of patients with splanchnic vein thrombosis (STV). In a single-center retrospective study of 128 patients with STV, clusters of abnormal megakaryocytes in bone marrow biopsy combined with endogenous erythrocyte colony formation were used as reference standards for a diagnosis of MPD. These two criteria allowed the diagnosis of MPDs at risk of aggravation in 25% (26 of 103) of patients with STV (41% in BCS; 23% in PVT). After a mean follow-up of 6.09 +/- 6.6 years, hematologic progression was confirmed in 23% of patients with the two criteria both positive, whereas neither progression nor features suggestive of MPD were observed in patients with the same concordant negative criteria. The combination of marked splenomegaly and platelet count > 200 x 10 (9)/L that was never observed in patients without MPD, constitutes a simple index for the suspicion of an underlying MPD, but the absence of an obvious splenic enlargement and normal or decreased platelet numbers may even be observed in patients with MPD-associated STV. In the absence of reliable indicators of the exact expansion of the myeloproliferative clone, the therapeutic management of STV-associated MPD is difficult to standardize. Owing to the suspected incidence on the prognosis of BCS of an associated MPD, the present watchful-waiting attitude proposed in MPD without obvious hematologic expression may be challenged.     

Comparative assessment of quantitative HIV viraemia assays.

OBJECTIVE: To compare two published methods for determining plasma viraemia in HIV-seropositive patients, with reference to a cellular viraemia assay. PATIENTS, PARTICIPANTS: Three patient groups were defined according to CD4 cell count: group I, less than 200 x 10(6)/l (23 patients); group II, 200-500 x 10(6)/l (18 patients); and group III, greater than 500 x 10(6)/l (13 patients). METHODS: The two reported methodologies were applied to all fresh samples, simultaneously and on the same day. RESULTS: The two techniques did not differ significantly in the detection of plasma viraemia: 82.3% of group I patients and 55% of group II patients were positive, while all group III patients were negative. Cellular viraemia was positive for 96% of the overall population. CONCLUSIONS: These results, obtained in a network of seven French laboratories involved in clinical trials, confirm that both plasma viraemia and cellular viraemia are useful virological markers.     

Peripheral blood vs bone marrow as a source for allogeneic hematopoietic stem cell transplantation.

In this randomized prospective study, we included 30 patients with different hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome or severe aplastic anemia) to compare peripheral blood stem cells (PBSC) (15 patients; mean age 23) and bone marrow (BM) (15 patients; mean age 21.8) as a source for allogeneic transplantation regarding the tempo of hematopoietic recovery and the incidence of acute graft-versus-host disease (GVHD). In the BM group, the median nucleated cell count harvested was 1.3 x 10(10), while in the PBSC group, the aphereses contained a median of 4.4 x 10(6) CD34+/kg recipient weight. PBSC transplantation (PBSCT) was associated with faster hematopoietic reconstitution measured as absolute neutrophil count (ANC) >0.5 x 10(9)/l (log-rank P value <0.0018) and platelet count >25 x 10(9)/l (log-rank P value <0.0098). Seven patients (46.7%) in the BM group vs only one patient (6.7%) in the PBSC group developed acute GVHD (P = 0.013). Therefore, we conclude that PBSCT is associated with faster hematopoietic recovery and the incidence of acute GVHD does not exceed that seen with BMT.     

Treatment of hepatitis C related thrombocytopenia with interferon alpha.

Thrombocytopenia is a common extrahepatic manifestation of hepatitis C (HCV) infection. Treatment with steroids may be effective, but can exacerbate the viral infection. Interferon alpha (INF) has documented efficacy in the treatment of HCV, but its use in the treatment of HCV thrombocytopenia is controversial. We treated eight patients with HCV-related thrombocytopenia, who had platelet counts of fewer than 50 x 10(9)/l (range: 16 to 46 x 10(9)/L) with INF 3 MU SQ three times a week. Planned duration of treatment was 24 weeks. Five patients had no evidence of hepatic cirrhosis, three had cirrhosis, and two had palpable splenomegaly. Only three patients tolerated the full course of treatment, and all three had improvement in their platelet counts to greater than 50 x 10(9)/l. Two other patients had improvement in platelet counts to more than 50 x 10(9)/l with shorter duration of treatment (six and 16 weeks, respectively). The mean increase in platelet count in the five responders was 44 x 10(9)/lL (range: 28 to 90 x 10(9)/l). The average peak platelet count in the responders was 81 x 10(9)/l (range: 62 to 136 x 10(9)/l). Duration of response ranged from four to 18+ months, with the shortest responses observed in the two patients treated with a shorter course of INF. Response was independent of the presence of cirrhosis. Responding patients had improvement in hepatic transaminases, reduction in cryoglobulin and anticardiolipin antibodies, and HCV plasma RNA when tested. Relapse was associated with an increase in these laboratory markers of HCV infection. We conclude that INF can be an effective treatment in patients with HCV-related thrombocytopenia.     

Patterns of platelet response in idiopathic TTP/HUS: frequency of declining platelet counts with plasma exchange and the recognition and significance of a pseudo refractory state

For thrombotic thrombocytopenic purpura (TTP), daily plasma exchange (TPE) is typically discontinued when the platelet count normalizes (>150 x 10(9)/L). We observed a decline in platelet count during TPE and in patients who appeared pseudo-refractory because of a platelet count plateau (100-150 10(9)/L range). In the present study, we evaluated platelet count trends in TTP patients. Retrospective review of TTP patients from 01/1999 to 12/2004 was completed. Patients were categorized based on platelet count trends: Group I, counts rose then decreased to levels <100 x 10(9)/L; Group II, counts declined following TPE initiation; Group III, counts rose continuously; Group IV, counts decreased after the count was >100 x 10(9)/L. Additionally, we identified pseudo-refractory patients caused by a platelet count plateau (>100 x 10(9)/L but <150 x 10(9)/L). We identified 60 TTP patients. Within Group I (17 patients/17 series/19.1% of total), the mean decrease in platelet count was 67.3% +/- 22.1% following initial rise. Within Group II (24 patients/25 series/28.1% of total), the mean decrease was 28% +/- 5.3% following presentation. Group III included 31 patients/39 series (43.8% of the total). Within Group IV (seven patients/eight series/9.0% of total), the mean decrease was 17.4% +/- 12.6% following a sustained rise >100 x 10(9)/L. With a declining platelet count and daily TPE, it is generally sufficient to stay the course and the decline will reverse. Our limited experience with pseudo-refractory patients supports discontinuing TPE when counts plateau between 100 and 150 x 10(9)/L when a therapy goal is a platelet count of 150 x 10(9)/L. Recognition of this pseudo-refractory state can minimize the risks of prolonged TPE and the risks of adjunct interventions.     

Changes in endogenous TPO levels during mobilization chemotherapy are predictive of CD34+ megakaryocyte progenitor yield and identify patients at risk of delayed platelet engraftment post-PBPC transplant

Patients with delayed platelet recovery post-PBPC transplant (PBPCT) are a high-risk group for thrombocytopenic bleeding and platelet transfusion dependence. Total CD34+ cell dosage has been proposed as the most important factor influencing the rate of platelet recovery. To achieve the shortest time to platelet engraftment, a minimum leukapheresis target of 10x10(6) CD34+ cells/kg was established for 30 patients. Of the 29 evaluable patients, 62% had rapid (group I: time to platelets >20x10(9)/l < or =10 days and 50x10(9)/l < or =14 days) platelet recoveries while 38% had delayed (group II: 20x10(9)/l >10 days and 50x10(9)/l >14 days) recoveries. Groups I and II were compared for: (1) pretreatment variables; (2) mobilizing capability of CD34+ cells and subsets including megakaryocyte (Mk) progenitors; (3) infused dose of these cells at transplant; (4) changes in endogenous levels of Mpl ligand (or TPO) during mobilization and myeloablative chemotherapy. Group II patients received significantly more platelet transfusions (6 vs. 2.1, P = 0.002) post-PBPCT, had a higher proportion of patients with a prior history of BM disease (64% vs. 6%, P = 0.001), and showed a reduced ability to mobilize differentiated (CD34+/38+, CD34+/DR+) and Mk progenitors (CD34+/42a+, CD34+/61+). Only the number of Mk progenitors reinfused at transplant was significantly different between the groups (group II vs. group I: CD34+/42a+ = 1.02 vs. 2.56x10(6)/kg, P = 0.013; CD34+/61+ = 1.12 vs. 2.70x10(6)/kg, P = 0.015). The ability to mobilize Mk progenitors correlated with percentage changes in endogenous levels of TPO from baseline to platelet nadir during mobilization chemotherapy (CD34+/42a+: r = 0.684, P = 0.007; CD34+/61+: r = 0.684, P = 0.007), with group II patients experiencing lower percentage changes. An inverse trend but no correlation was observed between serial TPO levels and platelet counts. TPO levels remained elevated in group II patients throughout a prolonged period of thrombocytopenia (median days to 50x10(9)/l = 25 vs. 11 for group I), indicating that delayed engraftment was not due to a deficiency of TPO but to a lack of Mk progenitor target cells. Our results show that the number of reinfused Mk progenitors is a better predictor of platelet engraftment than total CD34+ cell dosage. Small changes in endogenous TPO levels during mobilization predict for low Mk progenitor yields.     

Recovery of hematopoiesis after high-dose chemotherapy and peripheral blood stem cell autografts in children]

Hematopoietic recovery kinetics were evaluated in 34 children with therapy-refractory malignant tumors who underwent a total of 35 peripheral blood stem cell autografts (PBSCT) after marrow-ablative chemotherapy without total body irradiation. A negative correlation was found between the numbers of colony-forming units of granulocyte-macrophage (CFU-GM) infused per kilogram of the patients' body weight and the time of achieving an absolute granulocyte count (AGC) of 0.5 x 10(9)/l or a platelet count of 50 x 10(9)/l (granulocyte: r = -0.631, p less than 0.001, platelet: r = -0.590, p less than 0.001). The patients were classified into three groups; 14 patients who received less than 1 x 10(5) CFU-GM/kg (group A), 7 patients who received 1-3 x 10(5) CFU-GM/kg (group B), and 14 patients who received greater than or equal to 3 x 10(5) CFU-GM/kg (group C). The AGC recovered to 0.5 x 10(9)/l by 21 day in group A, 14 day in group B, and 10 day in group C. The platelet count recovered to 50 x 10(9)/l 102 in group A, 23 in group B, and 16 day in group C patients. The final platelet infusion was on day 60 in group A, day 12 in group B, and day 12 in group C. Transient decrease in the blood cell count developed in all patients 3 to 7 weeks after transplantation, and two cases developed reversible ITP. In the remaining patients, the recovered hematopoietic function was sustained for 1-48 months after transplant action.(ABSTRACT TRUNCATED AT 250 WORDS)     

Successful treatment with vincristine for an elderly patient with idiopathic thrombocytopenic purpura]

A 77-year-old female was referred to our hospital in March 1991 because of a severe bleeding tendency. Her blood count on admission was as follows: Hb 7.5 g/dl, WBC 4.6 x 10(9)/l with normal differentiation and platelet 2 x 10(9)/l. One month prior to admission, her blood count was normal. Initially, acute idiopathic thrombocytopenic purpura (ITP) was suspected, because of the acute onset of the bleeding tendency and thrombocytopenia. High dose intravenous immunoglobulin (400 mg/kg/day for 5 days) and bolus methylprednisolone (1 g/day for 3 days then tapered) were administered, starting March 13. Her platelet count had increased immediately on March 20 to 40 x 10(9)/l. However, platelet count decreased to 4 x 10(9)/l in the following two weeks. Her clinical course differed from that of typical acute ITP. Because the treatment with prednisolone was not effective, it was changed to intravenous infusion of vincristine (VCR) at a weekly dose of 1 mg for 6 weeks. The treatment was extremely effective, and her platelet count reached over 200 x 10(9)/l. The treatment was discontinued. Three weeks later, her platelet count decreased to 15 x 10(9)/l, the administration of VCR was resumed, and her platelet count recovered again. Throughout her clinical course, no side effect of VCR was noticed except for mild hypesthesia of the fingertips. VCR therapy was considered to be an useful treatment in elderly patients with ITP.     

Improvement of thrombocytopenia with disappearance of HCV RNA in patients treated by interferon-alpha therapy: possible etiology of HCV-associated immune thrombocytopenia

We evaluated the relationship between the severity of thrombocytopenia and the serum hepatitis C virus (HCV) RNA level to investigate the mechanism of thrombocytopenia in patients with HCV infection. Patients who had chronic hepatitis without splenomegaly were divided into two groups according to the platelet count, which were 18 patients with a platelet count < or =150 x 10(9)/L and 22 patients with a platelet count >150 x 10(9)/L. HCV RNA, platelet-associated immunoglobulin G (PAIgG), rheumatoid factor (RF), and other immunological parameters were measured and correlations were investigated. Patients in the low platelet group had higher levels of PAIgG, Th1 cells, thrombopoietin (TPO), and RF than those in the normal platelet group (textitP < 0.05). Twenty-two patients completed 6 months of IFN therapy and were followed for more than 1 yr afterwards. Twelve patients who responded to IFN therapy with clearance of HCV showed an increase of the platelet count, whereas the 10 patients who did not respond to IFN showed a decrease of the platelet count. The improvement of thrombocytopenia after interferon therapy suggests a contribution of HCV infection to this condition.     

Mobilization of CD34+ cells in elderly patients (>/= 70 years) with multiple myeloma: influence of age,prior therapy,platelet count and mobilization regimen

The mobilization of peripheral blood stem cells was studied in 984 multiple myeloma patients, including 106 patients aged >/= 70 years. Increasing age correlated inversely with CD34+ yield (P < 0.0001), but also with >/= 12 months of prior standard chemotherapy (P = 0.0001), < 200 x 10(9)/l platelets (P = 0.0006) premobilization and mobilization with growth factors only (P = 0.0001). After controlling for these age covariates, multivariate analysis identified /= 200 x 10(9)/l premobilization as favourable variables (both P < 0.0001), while increasing patient age remained an unfavourable factor (P = 0.0009). With both favourable variables, 85% of elderly patients collected >/= 4 x 10(6)/kg CD34+ cells in a median of one collection. The effect of age was incremental with no age threshold showing acceleration in the decline of CD34+ yield. Chemotherapy significantly increased CD34+ yield compared with growth factors only. However, the subgroup of patients with > 12 months prior therapy and premobilization platelet count < 200 x 10(9)/l mobilized as many CD34+ cells with granulocyte colony-stimulating factor (G-CSF) alone as with chemotherapy and haematopoietic growth factors. Increasing patient age had no effect on post-transplant neutrophil recovery, but significantly delayed platelet recovery (>/= 50 x 10(9)/l) if < 2 x 10(6)/kg CD34+ cells were infused, but this effect was eliminated completely with infusion of >/= 4 x 10(6)/kg CD34+ cells. Increasing age adversely affected CD34+ yield even with limited premobilization therapy, indicating that early collection is important in elderly patients.     

A prospective evaluation of normal mean platelet volume in discriminating hyperdestructive thrombocytopenia from hypoproductive thrombocytopenia

Bone marrow (BM) examination is the gold standard test in discriminating between hyperdestructive thrombocytopenia and hypoproductive thrombocytopenia. However, this procedure is invasive. Mean platelet volume (MPV) is simple and may be used as an alternative diagnostic test in distinguishing these two types of thrombocytopenia. All thrombocytopenic patients (platelet count: <150.0 x 10(9)/l), except those with congestive splenomegaly, thrombotic thrombocytopenic purpura, and disseminated intravascular coagulopathy, were enrolled into the study prospectively. The mean MPV of normal Thais (7.9 fl) was tested as a cutoff value. Any thrombocytopenic patient with MPV of >7.9 fl would be presumptively diagnosed as hyperdestructive thrombocytopenia, whereas one with MPV of 7.9 fl could predict hyperdestructive thrombocytopenia with a sensitivity of 82.3% (95% CI: 70.5-90.8), a specificity of 92.5% (95% CI: 79.6-98.4), a positive predictive value of 94.4% (95% CI: 84.6-98.8), a negative predictive value of 77.1% (95% CI: 62.7-88.0), and a likelihood ratio of 11.0. In conclusion, the mean MPV of normal Thais may be used as a cutoff value in distinguishing these two types of thrombocytopenia.     

Relationships between platelet counts, platelet volumes and reticulated platelets in patients with ITP: evidence for significant platelet count inaccuracies with conventional instrument methods

The platelet count has a primary role in the diagnosis and treatment of idiopathic thrombocytopenic purpura (ITP). This study analysed the accuracy of ITP patient platelet counts determined by Abbott CD-Sapphire (impedance/optical) and Bayer Advia 120 (optical) analyses, compared with a reference immunoplatelet method. Instrument platelet estimates showed broad equivalence in the higher range of observed values, but significant discrepancies against the immunoplatelet count were seen when platelet counts were <10 x 10(9)/l. CD-Sapphire mean platelet volume (MPV) results revealed increased (>12 fl) platelet volumes in eight of eight ITP patients with counts of <20 x 10(9)/l compared with 6/6 and 5/13 patients with platelet counts of 20-50 and >50 x 10(9)/l. In contrast, Bayer Advia MPV values showed no relationship with the platelet count. Increased reticulated platelets were associated with an increasing CD-Sapphire MPV (R(2) = 0.61) and a decreasing platelet count. High (>40%) reticulated platelet values were seen in 9/9 patients with immunoplatelet counts of <20 x 10(9)/l compared with 0/19 patients with platelet counts above 20 x 10(9)/l. There may be a need for caution in the interpretation of platelet counts in ITP patients obtained with conventional instrument methods, and therapeutic decisions should ideally be validated by reference immunoplatelet procedures.     

Current status and problem of platelet transfusion for hematopoietic diseases: results from a questionnaire survey

We carried out a survey on platelet transfusions performed in hospitals certified by the Japanese Society of Hematology. The average values of the pretransfusion platelet count (trigger value) for the day on which the transfusion was ordered, and the values on each day in the interval between the order and actual transfusion, were compared with the Guidelines. The average trigger value in aplastic anemia and myelodysplastic syndrome patients (A group) (1.41 x 10(4)/microl) for the same day on which the transfusion was ordered was higher than the Guideline, whereas those patients with hematological disorders undergoing chemotherapy (B group) and hematopoietic stem cell transplantation (C group), namely 2.08 x 10(4)/microl and 2.1 x 10(4)/microl, respectively, were acceptable values when compared with the Guidelines. On the other hand, in all groups, the transfusion trigger values at one or two days after ordering were higher than the Guidelines, being 2.56 x 10(4)/microl in the A group, 3.15 x 10(4)/microl in the B group, and 2.59 x 10(4)/microl in the C group. We have tried to formulate platelet count criteria for ordering a transfusion based on one day before the actual transfusion, because these platelet counts on ordering were relatively high. The criteria are 1.0-1.5 x 10(4)/microl in group A, 3.0 x 10(4)/microI in group B, and 3.0 x 10(4)/microl in group C. In order to perform platelet transfusion according to the Guidelines, the platelet count on ordering should be decreased as we proposed.     

Splenectomy in a case of splenic vein thrombosis unmasks essential thrombocythemia

We report a patient with splenic vein thrombosis (SVT) in whom splenectomy resulted in the unmasking of essential thrombocythemia (ET). He had portal hypertension with haematemesis, resulting in anaemia requiring repeated blood transfusions. Investigations revealed SVT. Following splenectomy, he suffered a transient ischaemic attack episode, associated with persistent thrombocytosis (> 2000 x 10(9)/l). Other myeloproliferative disorders were excluded and a diagnosis of ET was established. He responded to hydroxyurea but, due to financial constraints, he discontinued treatment and subsequently relapsed. The association of ET with SVT is rare and the diagnosis of ET was missed initially as the platelet count was normal prior to splenectomy.     

Diagnosis of essential thrombocythemia at platelet counts between 400 and 600x10(9)/L. Gruppo Italiano Malattie Mieloproliferative Croniche(GIMMC)

BACKGROUND AND OBJECTIVE: Diagnostic criteria for essential thrombocythemia (ET) remain essentially negative, that is, exclusion of other myeloproliferative diseases and causes of reactive thrombocytosis. A platelet count above 600x10(9)/L is still generally considered an absolute diagnostic criterion although new protocols for positive diagnostic criteria have recently been proposed, reducing the stringency of a definite platelet limit. This study demonstrates that a platelet count 600x10(9)/L is not a reliable diagnostic criterion for ET, especially in the early stages. DESIGN AND METHODS: An ongoing retrospective study by the GIMMC analyzed 2,316 ET patients diagnosed between 1986 and 1995. Of these 2,316 patients, diagnosed according to the PVSG criteria, 68 had a platelet count 600x10(9)/L and were analyzed separately; 37 out of 68 were excluded from this analysis because of a follow-up shorter than 2 years and/or because of treatment with myelosuppressive agents. The remaining 31 patients were the subjects of our study. RESULTS: After a median follow-up of 4.56 years (range 2-9.6 years) none of the 31 patients had a spontaneous decrease of platelets to the normal range. Transformation to a different chronic myeloproliferative disorders was never observed and no patient developed a condition known to produce reactive thrombocytosis. During follow-up, 23 patients (74%) were treated with anti-aggregating drugs, mainly aspirin. The disease did not evolve into acute leukemia in any patient, 1 had a thrombotic event and none presented hemorrhagic episodes. Median platelet count during follow-up was 534x10(9)/L (range 398-997x10(9)/L). INTERPRETATION AND CONCLUSIONS: Long term follow-up has documented that our 31 patients were correctly diagnosed as having ET, although platelet count was 600x10(9)/L. Our patients were probably in a early phase of their disease and following updated PVSG criteria would have been misdiagnosed leading to incomplete recognition of the natural history of the disease. Further, because an early diagnosis could also have a clinical relevance, our results outline the need for new criteria for the diagnosis of ET. The exclusion of patients with a platelet count between 400 and 600x10(9)/L may prevent patients, nevertheless at risk of vascular complications, from being treated.     

Very large amounts of peripheral blood progenitor cells eliminate severe thrombocytopenia after high-dose melphalan in advanced breast cancer patients

We analyzed the relationship between the reinfusion of large or very large amounts of peripheral blood progenitor cells (PBPC) and hematologic toxicity in twenty-one advanced breast cancer patients subjected to a myeloablative dose of melphalan at the end of a high-dose sequential chemotherapy (HDSC) program. We also evaluated the influence of the white blood cell (WBC) count to predict an optimal PBPC harvest after high-dose chemotherapy and growth factor priming. Twenty-one patients with high-risk or metastatic breast cancer sequentially received: high-dose cyclophosphamide (HD-Cy) and G-CSF followed by PBPC harvest, HD-methotrexate plus vincristine, HD-doxorubicin, cisplatin and finally HD-melphalan 200 mg/m2 (HD-L-PAM) followed by PBPC reinfusion. No growth factor was administered after HD-L-PAM. CD34+ cytofluorimetric analysis, WBC count and clonogenic assays were employed to monitor circulating cells and to analyze the PBPC harvest. Correlation between different PBPC doses and hematologic toxicity as well as leukocyte and platelet recovery time was attempted. Patients received a median number of 16 (4-25.1) x 10(6)/kg CD34+ cells, 81.3 (30.8-228) x 10(4)/kg CFU-GM and 4.2 (1.3-7.3) x 10(8)/kg nucleated cells (NC) after HD-L-PAM. The number of days with fewer than 1 x 10(9)/l leukocytes and 20 x 10(9)/l platelets were 6 (range 4-9) and 0 (range 0-3), respectively. The CD34+ cell dose significantly correlated with both platelet count nadir (r = 0.73) and time to 50 x 10(9)/l platelets (r = 0.7), but did not correlate with time to reach more than 1 x 10(9)/l WBC count (r = 0.2). In particular, we found that in 12 patients given very large amounts of CD34+ cells, ranging between 15.8 and 25. 1 x 10(6)/kg (V-LA-CD34+), the platelet nadir count never fell below 20 x 10(9)/l and platelet transfusions were not required. Conversely, nine patients who received only large amounts of CD34+ cells, ranging between 4 and 12 x 10(6)/kg (LA-CD34+), experienced a platelet nadir lower than 20 x 10(9)/l and required 2 days (range 1-4) to achieve independence from platelet transfusions (P = 0.001 and P = 0. 0005). The requirement for packed red blood cells (RBC) was 1.5 vs 3 units in the V-LA-CD34+ and LA-CD34+ groups respectively (P = 0.063). The analysis of 44 PBPC collections demonstrated that 29 aphereses performed with a WBC count <20 x 10(9)/l yielded a mean of 312 +/- 43 x 10(6) CD34+ cells and 1831 +/- 201 x 10(4) CFU-GM, whereas 15 collections performed with WBC count >20 x 10(9)/l yielded 553 +/- 64 x 10(6) CD34+ cells and 3190 +/- 432 x 10(4) CFU-GM (P = 0.004). In conclusion, our data suggests that V-LA-CD34+ eliminates severe thrombocytopenia and platelet transfusion requirements in breast cancer patients subjected to HD-L-PAM, and higher PBPC collections seems to coincide with WBC count higher than 20 x 10(9)/l after HD-Cy and G-CSF mobilization. These results justify a prospective study to establish whether large doses of CD34+ cells result in significant clinical benefits.     

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).     

Splenectomy for refractory thrombocytopenia in the antiphospholipid syndrome.

OBJECTIVE: Thrombocytopenia, usually mild, is one of the clinical criteria of the antiphospholipid syndrome (APS). Rarely, this disorder requires treatment and, due to the shared characteristics with idiopathic thrombocytopenic purpura (ITP), similar rules are followed. We report our experience in patients who required splenectomy after being refractory to steroids and immunosuppressive therapy. METHODS: Fifty-five APS patients with a platelet count of < 100 x 10(9)/l at least twice were analysed retrospectively. Therapeutic response or remission was considered when the platelet count was > 100 x 10(9)/l after 1 month and with no relapse on stopping or tapering the steroid dose. No response or refractory disease was defined as an absence of increase in platelet count, a total count that never exceeded 50 x 10(9)/l during treatment or when the dose requirements were such that the patient developed serious side-effects. RESULTS: Fifty patients were classified as having secondary APS associated with systemic lupus erythematosus (SLE) and five were identified as primary APS (PAPS). Splenectomy was performed in 11 cases (20%), two PAPS and nine SLE-APS, with an average time of 28 +/- 9 months after the development of thrombocytopenia. Eight patients were initially characterized as ITP (six SLE-APS, two PAPS) with an average time of 4.4 +/- 1.1 yr until the APS diagnosis. All but two were responsive to splenectomy. CONCLUSION: Splenectomy was required in 11 (20%) of the patients with APS-associated thrombocytopenia. There was a high rate of good and long-term response.