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.     

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.     

High-dose dexamethasone for splenectomy in patients with idiopathic thrombocytopenic purpura.

High-dose intravenous immune globulin (IV IgG) is currently the treatment of choice for patients with idiopathic thrombocytopenic purpura (ITP) who undergo splenectomy; however, this treatment is extremely expensive. We report on 13 ITP patients with severe thrombocytopenia (<20 x 10(9)/l) who were prepared for laparoscopic splenectomy with a 4-day oral course of high-dose (40 mg/day) dexamethasone (DEX). Four patients had an excellent response with platelet counts that increased to above 150 x 10(9)/l. Seven patients had a good response with a platelet count that increased to between 50 and 150 x 10(9)/l (median 121 x 10(9)/l). Two patients were resistant both to DEX and IV IgG. The operation was uneventful in all the patients, including the 2 who had resistant ITP and were operated on while their platelet count was very low (5 x 10(9)/l). Thus, high-dose DEX, which is an easy, effective and inexpensive treatment, is recommended for the preparation of ITP patients prior to splenectomy.     

5- to 16-year follow-up following splenectomy in chronic immune thrombocytopenic purpura in children

The long-term outcome after splenectomy in children with chronic immune thrombocytopenic purpura (ITP) has not been widely analyzed. We reviewed the medical records of 288 children and adolescents with chronic ITP between 1980 and 1996: 112 were splenectomized; 59 were steroid resistant and 42 were steroid dependent, and 11 were managed with repeated courses of intravenous immunoglobulin (IVIG). All had platelet counts (PCs) <30 x 10(9)/l with frequent bleeding episodes or persistent thrombocytopenia <10 x 10(9)/l. Ninety-eight patients (88%) were evaluated; 58 (60%) patients had never received immunotherapy for ITP following splenectomy. At 5 years, 44 (45%) remained in complete response (CR) and 34 (35%) in partial response (PR). In multivariate analysis, steroid-resistant patients were more likely to relapse after an initial CR (RR 5.2). CONCLUSION: The long-term CR was 45%; 60% had stable PCs >30 x 10(9)/l not requiring therapy. Most postsplenectomy relapses occurred during the 1st year. Initial response to steroids and IVIG prior to splenectomy was a predictor of long-term response to splenectomy.     

重组人血小板生成素治疗慢性难治性特发性血小板减少性紫癜的多中心临床试验

目的 评价国产重组人血小板生成素(rhTPO)对慢性难治性特发性血小板减少性紫癜(ITP)的疗效和安全性。方法 慢性难治性ITP患者皮下注射rhTPO 1.0μg/kg,1次/d,疗程14 d。结果 82例患者用药前血小板计数中位数为15.5(6.0-24.0)×109/L,给药起(5、7、15)d时分别升至27.5(16.0～47.0)×109/L、35.0(20.5-78.0)×109/L和77.0(41.8-119.5)×109/L,与用药前相比(P值均<0.01)。停药后血小板计数逐渐回落,至给药起第28天,血小板计数中位数降至76.5(35～120.3)×109/L,但仍明显高于治疗前(P<0.01)。近期有效率85.3％,其中显效58.5％(血小板≥100×109/L,无出血症状),良效26.8％(血小板升至50×109/L或较原水平上升30×109/L以上,无或基本无出血症状)。仅3例出现轻微临床不良反应。16例中1例在给药起21 d和28 d的血清中检测出低滴度抗TPO抗体,但不具有中和活性。结论 rhTPO可一过性升高慢性难治性ITP患者的血小板计数,不良反应轻微。     

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)     

Functional role of CD4+CD25+ regulatory T cells and transforming growth factor-beta1 in childhood immune thrombocytopenic purpura

CD4+CD25+ regulatory T cells (Tregs) are critical in maintaining self tolerance and preventing organ specific autoimmune diseases. Their role in childhood immune thrombocytopenic purpura (ITP), an immune disorder in which the production of platelet autoantibodies might be caused by cytokine network dysregulation, has not been clearly defined. Transforming Growth Factor-beta1 (TGF-beta1) has been suggested to mediate Tregs suppressive function. The aim of this study was to assess cell populations of CD4+CD25+ T regulatory cells as well as mRNA expression of TGF-beta1 level in peripheral blood of children with ITP and evaluate their possible role in prediction of disease severity and response to therapy. Thirty-three children with ITP (13 acute and 20 chronic cases) and 10 healthy controls were studied. CD4+CD25+ regulatory T cells were assessed in peripheral blood by flowcytometry. Expression of TGF-beta1 mRNA was examined by real-time quantitative polymerase chain reaction assay. The frequency of CD4+CD25+ Tregs was significantly decreased in acute and chronic ITP patients as compared to controls. Acute ITP patients had significantly lower percentage of Tregs compared with chronic ITP patients. Higher frequency of CD4+CD25+ Tregs was detected in chronic ITP patients with platelet count >100 x 10(9)/L compared with patients with platelet count <100 x 10(9)/L and in steroid responsive patients compared with steroid resistant patients. The expression of mRNA TGF-beta1 level was significantly lower in acute and chronic ITP patients compared with controls and in chronic ITP patients with pltc <100 x 10(9)/L in comparison with patients with pltc > 100 x l0(9)/L. A significant positive correlation was found between percentage of CD4+CD25+ Tregs and mRNA expression of TGF-beta1 in chronic ITP patients. In conclusion, immune regulation of TGF-beta1 by Tregs may play a fundamental role in the pathogenesis of childhood immune thrombocytopenic purpura. This might form a base for future specific immunomodulatory therapies for ITP.     

High prevalence of sustained remission of idiopathic thrombocytopenic purpura after Helicobacter pylori eradication: a long-term follow-up study

We studied the effect of Helicobacter pylori (H. pylori) eradication in 43 consecutive H. pylori-infected patients with idiopathic thrombocytopenic purpura. H. pylori was eradicated with antibiotics in 41 of them (95.3%). The difference between the mean platelet count before and after therapy was statistically significant (54.3 x 10(9)/l vs. 119.1 x 10(9)/l; P < 0.001). A sustained remission was observed in 20 patients (48.8%), after a median follow-up of 31.2 months. None of the patients still infected by H. pylori after therapy reached normal platelet values. The long-term follow-up confirms the efficacy of H. pylori eradication in H. pylori-infected ITP patients.     

A prospective, randomized trial of conventional, dose-accelerated corticosteroids and intravenous immunoglobulin in children with newly diagnosed idiopathic thrombocytopenic purpura

To determine the minimal essential treatment for childhood acute idiopathic thrombocytopenic purpura (ITP), a prospective, randomized trial was conducted focusing on hemorrhagic manifestation as well as platelet count. Subjects with a platelet count of <10 x 10(3)/microL or 10 to 29 x 10(3)/microL and mucosal bleeding (group 1) were randomly assigned to receive intravenous immunoglobulin (IVIg) at 1 to 2 g/kg, conventional oral prednisolone (o-PSL) (2 mg/kg for 2 weeks). parenteral methylprednisolone (mPSL) (5 mg/kg for 5 days), or pulsed parenteral methylprednisolone (PmPSL) (30 mg/kg for 3 days). Subjects with a platelet count of 10 to 29 x 10(3)/microL without mucosal bleeding (group 2) were randomized to receive either o-PSL or no treatment. In subjects with a platelet count of 30 x 10(3)/microL or higher (group 3), patients undergoing no specific treatment were monitored. In group 1, IVIg offered faster platelet enhancement compared with o-PSL and mPSL, although neither mPSL no PmPSL showed any advantage, even over o-PSL. Platelet response was uniformly excellent when pretreatment platelet coun was > or = 10 x 10(3)/microL. Furthermore, the presence or absence of mucosal bleeding in subjects with a platelet count <10 x 10(3)/microL had no effect on the response to treatment. In group 2, platelet increase was indifferently attained with or without o-PSL. These data suggest that childhood acute ITP with a platelet count > or = 10 x 10(3)/microL may be left untreated or may be treated with o-PSL when mucosal bleeding is evident, whereas for those with a platelet count <10 x 10(3)/microL, IVIg is the most predictable platelet enhancer. Thus, a platelet count of 10 x 10(3)/microL seems to be informative enough to decide whether to treat childhood acute ITP.     

Very severe thrombocytopenia and fragmentation hemolysis mimicking thrombotic thrombocytopenic purpura associated with a giant intracardiac vegetation infected with Staphylococcus epidermidis: role of monocyte procoagulant activity induced by bacterial supernatant

The pathogenesis of very severe thrombocytopenia in bacterial endocarditis is uncertain. We report a 50-year-old male with platelet counts < 10 x 10(9)/l and fragmentation hemolysis complicating Staphylococcus epidermidis pacemaker endocarditis with a giant vegetation. Antibiotics, corticosteroids, high-dose intravenous gammaglobulin, and plasmapheresis (for initially-suspected thrombotic thrombocytopenic purpura) failed to produce significant platelet count increase. However, therapeutic-dose heparin anticoagulation was associated with a platelet count increase from <10 to approximately 40 x 10(9)/l, with parallel reduction in thrombin-antithrombin complexes (from 8.9 to 3.5 microg/l), facilitating surgical intervention. The thrombocytopenia promptly resolved following surgical removal of the vegetation. Culture supernatant from S. epidermidis isolated from the patient's blood induced monocytes to express procoagulant activity (assessed by factor Xa generation) equivalent to lipopolysaccharide (1 microg/ml), with half-maximal activation seen with culture supernatant diluted to 1:12,800. These data are consistent with previous animal models of endocarditis demonstrating staphylococci-induced procoagulant changes in monocytes. This case demonstrates that heparin anticoagulation can be therapeutic in infective endocarditis-associated severe thrombocytopenia in a non-bleeding patient, and that such therapy may ameliorate the platelet count enough to permit surgical intervention.     

Rituximab therapy for chonic and refractory immune thrombocytopenic purpura: a long-term follow-up analysis

The aim of this study was to evaluate the long-term response to rituximab in patients with chronic and refractory immune thrombocytopenic purpura (ITP). Adults with ITP fail to respond to conventional therapies in almost 30% of cases, developing a refractory disease. Rituximab has been successfully used in these patients. We used rituximab at 375 mg/m2, IV, weekly for a total of four doses in 18 adult patients. Complete remission (CR) was considered if the platelet count was >100 x 10(9)/l, partial remission (PR) if platelets were >50 x 10(9)/l, minimal response (MR) if the platelet count was >30 x 10(9)/l and <50 x 10(9)/l, and no response if platelet count remained unchanged. Response was classified as sustained (SR) when it was stable for a minimum of 6 months. Median age was 43.5 years (range, 17 to 70). Median platelet count at baseline was 12.5 x 10(9)/l (range, 3.0 to 26.3). CR was achieved in five patients (28%), PR in five (28%), MR in four (22%), and two patients were classified as therapeutic failures (11%). Two additional patients were lost to follow-up. The median time between rituximab therapy and response was 14 weeks (range, 4 to 32). SR was achieved in 12 patients (67%). There were no severe adverse events during rituximab therapy. During follow-up (median, 26 months; range, 12 to 59), no other immunosuppressive drugs were used. In conclusion, rituximab therapy is effective and safe in adult patients with chronic and refractory ITP. Overall response rate achieved is high, long term, and with no risk of adverse events.     

The long-term efficacy of Helicobacter pylori eradication therapy in patients with idiopathic thrombocytopenic purpura

BACKGROUND AND AIM: A beneficial effect of Helicobacter pylori (H. pylori) eradication in patients with H. pylori-positive idiopathic thrombocytopenic purpura (ITP) has been reported by several investigators; however, it was not clear whether the recovered platelet count after H. pylori eradication was maintained for a long period. METHOD: Thirty-eight ITP patients who were examined for H. pylori infection were assessed. H. pylori-positive patients received a standard antibiotic therapy for H. pylori eradication. We investigated the long-term effect of H. pylori eradication on platelet recovery in patients with H. pylori-positive ITP. RESULTS: Of the 38 ITP patients, 26 (68.4%) were positive for H. pylori. The response rate of platelet recovery was 56.5% (13/23 patients). Twelve patients showed complete response (CR) and one showed partial response (PR). The mean platelet counts 6 months after eradication significantly increased from 31 x 10(9)/L to 129 x 10(9)/L in 23 H. pylori-eradicated patients (P < 0.001). The median platelet counts of responders 1, 2, 3, and 4 years after eradication were 168 x 10(9)/L (n = 10), 193 x 10(9)/L (n = 9), 168 x 10(9)/L (n = 7), and 243 x 10(9)/L (n = 4) after a mean follow-up of 25.8 months. CONCLUSION: Eradication therapy for H. pylori-positive patients with ITP was effective and a favorable effect was maintained for long periods.     

Chronic thrombocytopenia of childhood: use of non-invasive methods in clinical evaluation

OBJECTIVES: An unselected group of 21 children with chronic thrombocytopenia was investigated to understand the patients' platelet abnormality better. METHODS: Platelet counts, mean platelet volumes (MPV), membrane glycoproteins and Fcgamma receptor type IIA (FcgammaRIIA) polymorphism H131R, reticulated platelets (% RP), antiplatelet antibodies and plasma thrombopoietin (TPO) were measured. RESULTS: Sixteen patients had idiopathic thrombocytopenic purpura (ITP) (group 1: platelets < 50 x 10(9)/L, n = 6; group 2: 50-99 x 10(9)/L, n = 4; group 3: 100-149 x 10(9)/L, n = 4; group 4: splenectomised patients with normal platelet counts, n = 2). Five patients had familial thrombocytopenia. Six healthy children were studied as a reference. In the 19 thrombocytopenic patients, the platelets were significantly larger and % RP and TPO levels were significantly higher than those in the controls. Increased megakaryocytosis at diagnosis was associated with larger MPV and higher % RP but not with platelet level or TPO. The % RP was remarkably high in all ITP patients of group 1 indicating a brisk production of platelets despite low peripheral count. In all patients with familial thrombocytopenia, TPO was increased suggesting that the syndrome was not because of defective TPO production. The distribution of FcgammaRIIA alleles in the patients was similar to that in the controls. CONCLUSIONS: A combined application of % RP and TPO could be helpful in classifying patients with chronic thrombocytopenia into different categories. The observations may be of value in the clinical evaluation of ITP patients and lead to avoidance of invasive examinations at least in some patients.     

Pattern of platelet-associated immunoglobulin (classes and IgG subclasses) in childhood immune thrombocytopenic purpura

Platelet-associated Ig classes and IgG subclasses were studied by a semiquantitative platelet ELISA test in 17 children with immune thrombocytopenic purpura (ITP). An elevation of PAIg was found in 94% of the children. In nearly all cases increased amounts of PAIgG of subclass G1 was seen, and in half of the cases increased amounts of PAIgM were also seen. No statistical difference in the composition of PAIg classes and PAIgG subclasses in acute and in chronic ITP was found. However, a correlation of increased amount of PAIgG3 and very low platelet count (20 x 10(9)/l) was observed.     

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.     

Effects of prednisone and splenectomy in patients with idiopathic thrombocytopenic purpura: only splenectomy induces a complete remission

Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous disease, whereby it is unclear if and in which way prednisone and splenectomy affect the platelet kinetics leading to a complete remission. To determine the effects of prednisone and splenectomy on the mean platelet life (MPL) and platelet production, platelet kinetic studies with Indium-111 tropolonate-labeled autologous platelets were performed in patients with ITP ( n=41). In 17 patients platelet kinetic studies were performed before and during prednisone treatment, and in 24 patients before and after splenectomy. MPL increased after prednisone therapy only in patients ( n=13) with a full recovery (FR, platelets >150 x 10(9)/l) and partial recovery (PR, 50 x 10(9)/l 相似文献   

Long-term follow-up of chronic autoimmune thrombocytopenic purpura refractory to splenectomy: a prospective analysis

Splenectomy remains the most effective treatment of chronic autoimmune idiopathic thrombocytopenia (ITP) (i.e. of > 6 months duration). Treatment of patients refractory to splenectomy (with absence of response or relapse after initial response) is difficult, and their long-term outcome is not well known. Over a 10-year period, 183 patients with chronic ITP were splenectomized including 158 adults and 25 children ( 100 x 10(9)/l, nine of them without treatment and 27 of them with low-dose steroids or azathioprine; six (13%) remained moderately thrombocytopenic (35 x 10(9)/l to 100 x 10(9)/l platelets); the last five patients, without response to any treatment (up to six regimens), remained severely thrombocytopenic (platelets < 20 x 10(9)/l), and three of them died from bleeding. Twenty-seven (57%) of the 47 refractory cases required at least one hospitalization, in the majority of cases for intravenous immunoglobulin (IVIg) infusions. Seven of the refractory cases occurred in children. Six of them subsequently reached platelet counts > 100 x 10(9)/l, but one died from bleeding. Our findings confirm the overall favourable long-term prognosis of chronic ITP refractory to splenectomy.     

Reduced transforming growth factor-beta1 production by mononuclear cells from patients with active chronic idiopathic thrombocytopenic purpura

Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which activated T-helper (Th) cells and different Th-cell cytokines might play an important role. We have recently reported that chronic ITP patients in remission had elevated plasma levels of the Th3 cytokine transforming growth factor-beta1 (TGF-beta1), possibly as a part of a bystander immune suppression. In the present study we found that, in ITP patients with active disease [platelet count (plc) < 50 x 10(9)/l], mitogen-stimulated peripheral blood mononuclear cells (PBMC) had a significantly reduced production of TGF-beta1 (444 +/- 178 pg/ml; n = 6) compared with patients with plc 50-150 x 10(9)/l (1293 +/- 374 pg/ml; n = 9; P < 0.05), patients with plc >150 x 10(9)/l (1894 +/- 244 pg/ml; n =12; P <0.005) and healthy controls (1698 +/- 241 pg/ml; n = 10; P < 0.01). Nineteen per cent of ITP patients expressed a platelet-induced PBMC proliferation. Surprisingly, 22% of the ITP patients had a PBMC proliferation below the normal range, i.e. a suppressed proliferation in the presence of platelets; five of these six patients had active disease. In summary, this study demonstrated that chronic ITP patients with active disease had reduced PBMC production of the Th3 cytokine TGF-beta1. This result gives further support to the theory that chronic ITP in active phase is associated with a downregulated Th3-response.     

Analysis of outcome of laparoscopic splenectomy for idiopathic thrombocytopenic purpura by platelet count

Laparoscopic splenectomy (LS) is now performed routinely in patients with idiopathic thrombocytopenic purpura (ITP) refractory to the medical treatment. Low preoperative platelet count was deemed to be a contraindication for a laparoscopic approach; however, there is no data reporting the outcome in those patients. We aimed to evaluate the influence of the preoperative platelet count on the operative and postoperative course and complication rate. Retrospective cohort study that was conducted in tertiary care university-affiliated medical center and included 110 consecutive patients who underwent LS. All patients were divided into three groups by their preoperative platelet counts: 50 x 10(9)/L (n = 80). The outcome and the influence of preoperative factors predictive of complications, blood transfusion, and length of stay were compared between the groups. Patients with a platelet count of 20 x 10(9)/L before surgery. Patients with counts >20 x 10(9)/L can safely undergo LS.     

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.