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S Cortelazzo

Publications and source records attributed to S Cortelazzo.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence of HCV infection in nongastric marginal zone B-cell lymphoma of MALT.

BACKGROUND: Hepatitis C virus (HCV) infection is frequently associated with B-cell non-Hodgkin's lymphomas. We investigated the prevalence of HCV infection in nongastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) in order to define the relationship between the viral infection and the presenting features, treatment, and outcome. METHODS: We retrospectively studied 172 patients with a histological diagnosis of marginal zone B-cell lymphoma of MALT, except for stomach, and with available HCV serology, among a series of 208 patients. RESULTS: HCV infection was documented in 60 patients (35%). Most HCV-positive patients (97%) showed a single MALT organ involvement. HCV-positive patients showed a more frequent involvement of skin (35%), salivary glands (25%), and orbit (15%). The majority of stage IV HCV-positive patients (71%) had a single MALT site with bone marrow involvement. The overall response rate was similar in HCV-positive (93%) and HCV-negative patients (87%). Overall survival (OS) and event-free survival (EFS) did not differ according to HCV infection. In multivariate analysis, advanced disease (stage III-IV) was associated with a poorer OS (P = 0.0001), irrespective of HCV serostatus. CONCLUSIONS: This study shows that nongastric marginal zone lymphomas are characterized by a high prevalence of HCV infection. Patients with involvement of a single MALT site have the highest prevalence of HCV. HCV-positive nongastric lymphomas of MALT show an indolent course similar to HCV-negative patients and seem an ideal target for exploiting the antilymphoma activity of antiviral treatments.

Antibodies, Viral↗
PubMed2006

Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation.

We report the results of two prospective phase II studies investigating the role of high-dose sequential chemotherapy, followed by autologous stem cell transplantation (ASCT) in 62 patients with advanced stage peripheral T-cell lymphomas (PTCLs) at diagnosis. Conditioning regimen consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) or carmustine, etoposide, Ara-C and melphalan followed by peripheral blood stem cell autografting. In an intent-to-treat analysis, 46 out of 62 patients (74%) completed the whole programme, whereas 16 patients did not undergo ASCT, mainly because of disease progression. At a median follow-up of 76 months, the estimated 12-year overall (OS), disease-free and event-free survival (EFS) were 34, 55 and 30%, respectively. OS and EFS were significantly better in patients with anaplastic lymphoma-kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL), as compared with the remaining PTCL. Multivariate analysis showed that patients attaining complete remission (CR) before ASCT had a statistically significant benefit in terms of OS and EFS (P<0.0001). Overall treatment-related mortality rate was 4.8%. In conclusion, our findings indicate (1) up-front high-dose therapy and ASCT are feasible, but could induce a high rate of long-term CR only in patients with ALK-positive ALCL and (2) the achievement of CR before autografting is a strong predictor of better survival.

Adult↗
PubMed2004

Anthracycline-based chemotherapy as primary treatment for intravascular lymphoma.

BACKGROUND: Optimal therapeutic management of intravascular lymphoma (IVL) lacks precise guidelines. PATIENTS AND METHODS: The clinico-pathological features of 38 HIV-negative patients with IVL were reviewed to define efficacy of chemotherapy in these malignancies. Clinical characteristics of 22 patients treated with chemotherapy and of 16 untreated patients were compared in order to understand better the impact and causes of potential patient selection. RESULTS: Median age was 70 years (range 34-90), with a male/female ratio of 0.9; 23 (61%) patients had Eastern Cooperative Oncology Group performance status (ECOG-PS) > 1; 21 (55%) had systemic symptoms. Cutaneous lesions and anemia were significantly more common among patients treated with chemotherapy; central nervous system (CNS) and renal involvement were significantly more common among untreated patients. Chemotherapy was associated with a response rate of 59% and a 3-year overall survival of 33 +/- 11%. Five of six patients with CNS involvement received chemotherapy: four of them died early; only one patient, treated with adriamycin, cyclophosphamide, vincristine, methotrexate, bleomycin and prednisolone (MACOP-B) followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), was alive at 19 months. High-dose chemotherapy supported by ASCT was indicated at diagnosis in another patient (43 years of age, stage I), who was alive at 71 months, and at relapse after cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in two patients who died early after transplantation. PS < or = 1, disease limited to the skin, stage I, and use of chemotherapy were independently associated with better outcome. CONCLUSIONS: Anthracycline-based chemotherapy is the standard treatment for IVL. However, survival is disappointing, with a relevant impact of diagnostic delay and lethal complications. More intensive combinations, containing drugs with higher CNS bioavailability, are needed in cases with brain involvement, and the role of high-dose chemotherapy supported by ASCT should be further investigated in younger patients with unfavorable features.

Adult↗
PubMed2003

Patterns of outcome and prognostic factors in primary large-cell lymphoma of the testis in a survey by the International Extranodal Lymphoma Study Group.

PURPOSE: To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell lymphomas (DLCL). PATIENTS AND METHODS: A retrospective international survey of 373 patients with primary testicular DLCL. RESULTS: Most patients presented with localized disease (stage I to II), and the median age at diagnosis was 66 years (range, 19 to 91 years). Anthracycline-based chemotherapy was administered to 255 patients (68%), and prophylactic intrathecal chemotherapy was given to 68 patients (18%); 133 patients (36%) received prophylactic scrotal radiotherapy. Median overall survival was 4.8 years, and median progression-free survival was 4 years. The survival curves showed no clear evidence of a substantial proportion of cured patients. A favorable international prognostic index score (IPI), no B-symptoms, the use of anthracyclines, and prophylactic scrotal radiotherapy were significantly associated with longer survival at multivariate analysis. However, even for patients with stage I disease and good-risk IPI, the outcome seems worse than what was reported for DLCL at other sites. At a median follow-up of 7.6 years, 195 patients (52%) had relapsed. Extranodal recurrence was reported in 140 cases. Relapses in CNS were detected in 56 patients (15%) up to 10 years after presentation. A continuous risk of recurrence in the contralateral testis was seen in patients not receiving scrotal radiotherapy. CONCLUSION: Testicular DLCL is characterized by a particularly high risk of extranodal relapse even in cases with localized disease at diagnosis. Anthracycline-based chemotherapy, CNS prophylaxis, and contralateral testicular irradiation seem to improve the outcome. Their efficacy is under evaluation in a prospective clinical trial.

Adult↗
PubMed2002

Rituximab: enhancing stem cell transplantation in mantle cell lymphoma.

Mantle cell lymphoma (MCL) responds poorly to standard chemotherapy regimens used in non-Hodgkin's lymphoma. As a result, a combination of high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) is being investigated in patients with MCL. So far, however, there is no evidence for long-term remission -- believed, in part, to be due to contamination of the transfusion product with residual cancer cells. Many ex-vivo purging methods have been developed to remove tumour cells, but these are complicated, time-consuming and expensive. This study describes an in vivo purging method using rituximab to produce a tumour-free stem cell product for re-infusion following HDT. The regimen is split into a purging phase and a myeloablative phase, which together consist of four-step high-dose sequential chemotherapy (sHDT) and six infusions of rituximab immunotherapy. The sHDT comprises cyclophosphamide, cytosine arabinoside, melphalan and mitoxantrone plus melphalan. There are two separate stem cell harvests and three reinfusions. In a pilot study 28 patients with untreated MCL received standard chemotherapy followed by sHDT with rituximab in vivo purging. Preliminary results indicate that in PCR analyses of leukaphereses from 20 assessable patients, 100% lymphoma-negative harvests were achieved following in vivo purging. PCR analyses of the bone marrow following the four-step high-dose regimen with purging and transplantation showed that all patients achieved molecular remission. After a median follow-up of 22 months (range 10-42 months), two patients had died while 26 were alive and disease free. This method allows efficient in vivo purging in the context of an effective chemotherapy regimen and may have a role as first-line therapy in MCL patients who respond poorly to standard treatment.

Antibodies, Monoclonal↗
PubMed2002

Relevance of intraocular involvement in the management of primary central nervous system lymphomas.

BACKGROUND: Reported data regarding intraocular lymphoma (IOL) management are anecdotal. Cases of IOL included in an international multicentre series of 378 immunocompetent patients with primary central nervous system lymphomas (PCNSLs) were reviewed. PATIENTS AND METHODS: Staging included slit-lamp examination in 170 patients: IOL was diagnosed in 22 cases (13%). A concomitant brain lesion was detected in 21 cases. Planned treatment was chemotherapy followed by radiotherapy in 13 cases, chemotherapy alone in three and radiotherapy, followed by or not by chemotherapy in five; one patient was not treated. Chemotherapy included high-dose methotrexate in 12 cases. Ten patients received intrathecal chemotherapy. Radiotherapy consisted of whole brain irradiation, followed by or not by a tumour bed boost; ocular irradiation was planned in 15 cases. Irradiation in one patient without brain lesions was limited to the orbits only (50 Gy). RESULTS: IOL was positively correlated to systemic symptoms and meningeal disease. Fifteen patients (71%) achieved an objective response; 16 patients experienced a failure (2-year failure-free survival 34+/-10%). Failures involved the eyes in eight cases, with a 2-year time to ocular relapse of 59+/-11%. Ocular failure was less common in patients treated with chemotherapy plus ocular irradiation and was associated with a significantly shorter survival. Seven patients are alive [median follow-up 53 months, 2-year overall survival (OS): 39+/-11%] , five of whom were treated with ocular irradiation. The patient with isolated IOL is alive and disease-free at 14 months. OS of the entire series was similar to that of PCNSL patients with negative slit-lamp examination. CONCLUSIONS: IOL is usually associated with concomitant brain disease and shows a survival similar to that of the rest of PCNSLs. Chemotherapy combined with ocular irradiation resulted in better control of ocular disease, which seems to be associated with survival. In view of the potential role of ocular irradiation, the use of chemotherapy alone in phase II trials should be critically reconsidered in PCNSL patients with ocular disease.

Adolescent↗
PubMed2001

Intensification of salvage treatment with high-dose sequential chemotherapy improves the outcome of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma.

The aim of the present study was to retrospectively evaluate whether a high-dose sequential chemotherapy programme (HDS: cyclophosphamide, methotrexate, etoposide) administered prior to autologous transplantation could optimize the salvage of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma. Between 1985 and 1999, 103 patients (median age 43 years, range 16-65) from eight Italian centres and one Swiss centre, with refractory (n = 38) or relapsed (n = 65) diffuse large B-cell and T-cell lymphoma, were treated using HDS followed by high-dose regimens with autologous haematopoietic stem cell transplantation. Eighty-three patients responded to the HDS regimen (81%, 95% C.I., 73- 88%) and 79 eventually achieved a complete response (CR) after autotransplantation (90%, 95% C.I., 81- 96%). None of 20 cases resistant to HDS attained CR. Treatment-related mortality was 4%. After a median follow-up of 24 months (range 6-174 months), 3-year estimates of overall survival, event-free survival and disease-free survival were 47% (95% C.I., 36-59%), 44% (95% C.I., 34-54%) and 64% (95% C.I., 50-74%) respectively. Multivariate analysis showed that chemosensitivity to HDS represented the strongest predictor of both CR and survival. This retrospective study shows that salvage treatment using HDS had relatively low toxicity and was associated with remarkable response rates, allowing further effective therapy with high-dose autograft programmes.

Adolescent↗
PubMed1999

Clinical outcome after autologous transplantation in non-Hodgkin's lymphoma patients with high international prognostic index (IPI).

BACKGROUND: Dose intensification and autologous stem cell transplantation as front-line therapy in non-Hodgkin's lymphoma patients (NHL) is a matter for debate, although preliminary data suggest a role for it in patients at high risk of resistance or relapse according to the international prognostic index (IPI). PURPOSE AND STUDY DESIGN: To compare retrospectively the clinical outcome of two cohorts of NHL patients with high-risk IPI treated with MACOP-B for 12 weeks (38 patients) or high-dose chemotherapy (44 patients) including eight weeks of MACOP-B, one or two intensification cycles with mitoxanthrone, dexamethasone, high-dose ara-C and finally BEAM chemotherapy with autologous hemopoietic progenitor cell transplantation. RESULTS: The actuarial estimate of event (progression, relapse or death)-free survival (EFS) at three years was better (58% vs. 41%, P = 0.08) for patients treated with intensive regimen even though the overall survival did not show a statistically significant difference (63% vs. 50%, P = 0.27). Multivariate analysis showed that the high-dose chemotherapy program was the only independent variable correlating with a reduction in the event rate. CONCLUSION: Early autologous stem-cell transplantation might improve the clinical outcome of high-risk patients according to IPI.

Adolescent↗
PubMed1999

Stage-modified international prognostic index effectively predicts clinical outcome of localized primary gastric diffuse large B-cell lymphoma. International Extranodal Lymphoma Study Group (IELSG)

BACKGROUND: The definition of prognostic parameters in early stages of gastric lymphoma is still controversial. The aim of this retrospective analysis was to assess the value of the stage-modified international prognostic index (IPI) in predicting the outcome of a large, consecutive series of patients with PGL of diffuse large B-cell histology (DLCL). PATIENTS AND METHODS: Three hundred twelve consecutive, newly-diagnosed, patients with localized PGL (stages I-IIE according to the 'Lugano staging system for GI lymphomas') referred from April 1972 to December 1997 to eight Italian and one Swiss centers were reviewed and their outcomes updated to June 1998. One hundred three patients were treated with single-modality therapy, while two hundred four received combined-modality treatment, most of which included surgery and short-term chemotherapy. RESULTS: After a median follow-up of 66 months (range 0.6-300 months), 195 (64%) were alive in first continuous complete remission (CCR). The five-year estimates of overall survival (OS) and event-free survival (EFS) were 75% and 67%, respectively. OS and EFS varied according to IPI, from, respectively, 90% and 82% for patients with 0-1 risk factors, to 40% and 35% for patients with > or = 3 risk factors (P = 0.00001). Cox regression analysis showed that IPI was the strongest predictor of survival. CONCLUSIONS: This study shows that stage-modified IPI is an effective predictive model in patients with primary DLCL of the stomach, enabling identification of patients with significantly different outcomes.

Adolescent↗
PubMed1998

Aspirin increases the bleeding side effects in essential thrombocythemia independent of the cyclooxygenase pathway: role of the lipoxygenase pathway.

Acetylsalicylic acid (ASA) is currently recommended as an antithrombotic for patients with essential thrombocythemia (ET) who are at an increased risk of thrombotic events. However, ASA is also associated with an increased risk of bleeding in these patients as compared to the risk of bleeding in other patients treated with ASA. Recent data suggest that while ASA inhibits platelet thromboxane A2 (TxA2) synthesis in all individuals, ASA has little effect or inhibits the lipoxygenase pathway (i.e., 12-hydroxyeicosatetranoic acid or 12-HETE synthesis) in some individuals, and enhances 12-HETE synthesis in others. These differential effects are associated with a pronounced prolongation of the bleeding time vs. no prolongation of the bleeding time, respectively, i.e., in ASA responders and ASA nonresponders, respectively. To determine if the increased risk of ASA-induced bleeding seen in ET patients is associated with an effect on 12-HETE synthesis, we compared the relative effects of ASA on the bleeding time, platelet TxA2 and 12-HETE synthesis, and platelet aggregation and adhesion in ET patients and healthy volunteers. ASA (300 mg, taken orally) prolonged the bleeding time in 82% of the ET patients but only 27% of the healthy volunteers although platelet TxA2 synthesis and ADP- and collagen-induced aggregation were inhibited significantly in both groups. In contrast, platelet 12-HETE synthesis was unchanged and platelet adhesion was decreased in those patients and volunteers whose bleeding times were prolonged by ASA, whereas platelet 12-HETE synthesis was increased significantly and platelet adhesion was unaffected in those patients and volunteers whose bleeding times were not prolonged, and in some cases shortened by ASA. These results confirm previous data that demonstrate that ASA has different effects on platelet 12-HETE synthesis and platelet adhesion in different individuals, i.e., inhibitory or no effect in ASA responders (in whom ASA prolonged bleeding) vs. enhancing effects in ASA nonresponders (in whom ASA did not prolong bleeding). These results also indicate that there is a greater percentage of ASA responders in patients with ET than that seen in the general population, a difference that is associated with an effect of ASA on the lipoxygenase pathway. This may explain the increased bleeding side effects seen in the ET patient population.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1998

Short course infusional idarubicin plus intermittent cytarabine and etoposide for refractory hematologic malignancies: clinical and preliminary pharmacological results.

BACKGROUND AND OBJECTIVE: Idarubicin (IDA) is relatively immune to the multidrug resistance P-gp mechanism that is frequently expressed in recurrent and refractory hematologic malignancies. Owing to rapid metabolism in vivo, a continuous infusion (CI) of IDA might prolong exposure time to the parent drug rather than its more P-gp susceptible alcohol metabolite. For this reason we developed a brief retreatment schedule incorporating CI IDA in order to obtain clinical as well as preliminary pharmacological data in patients with refractory leukemias and lymphomas. DESIGN AND METHODS: Eligible patients had either advanced-stage acute myeloid or lymphoid leukemias (AML, ALL) or high-grade non-Hodgkin's lymphomas (NHL) which failed curative-intent frontline or salvage regimens in use at our institution during the study period (July-October 1992). CI IDA 5 mg/m2/d was employed together with intermittent (every 8 hours) intermediate-dose cytarabine (500 mg/m2) and etoposide (200 mg/m2); all drugs were given for 2-4 days. A preliminary pharmacokinetic evaluation of CI IDA was carried out in three patients, including a comparison with bolus delivery in one. The in vitro effects of CI-type vs bolus-type IDA delivery in terms of intracellular IDA accumulation and related pro-apoptotic activity were assessed in P-gp- and P-gp+ human leukemic CEM cells by means of cytofluorimetry (IDA fluorescence intensity = FI, annexin V expression), with and without the addition of P-gp inhibitor cyclosporin A (CsA). RESULTS: Complete (2) or partial (4) responses were achieved in a total of 12 patients (17% and 33%, respectively), despite prior treatments with anthracyclines (100% of cases) and cytarabine-etoposide (33% of cases). Hematological toxicity caused the duration of treatment to be reduced from 4 days to 2 days after the first 4 patients. The procedural death rate was 42% (5/12), which was probably related in part to the sum of adverse prognostic characteristics: median patient age 55 years, two-thirds of cases having previously failed second/third-line regimens. The pharmacokinetic study showed an increased plasma AUC value with CI IDA in one patient (2.9-fold increase vs bolus delivery) due to the prolonged presence of low IDA plasma levels (10-20 ng/mL vs 50 ng/mL), as seen in two other cases as well. On the other hand, the in vitro study did not prove to be in favor of CI IDA because the FI threshold (> 1500 units) associated with increased apoptosis of P-gp+ cells (> 10%) was achieved only with bolus-type IDA exposure (50 ng/mL for 30') plus CsA. INTERPRETATION AND CONCLUSIONS: This short regimen demonstrated activity against end-stage leukemias and lymphomas and might prove to be more effective and less toxic in younger patients and in those with less advanced disease. In view of the results from plasma pharmacokinetics and in vitro intracellular IDA accumulation and apoptosis assays in lymphoblastic CEM cells, CI IDA 5 mg/m2/day may not represent a better therapeutic option than a rapid bolus injection, particularly in P-gp+ neoplasms. If obtaining an adequate intracellular drug concentration is the primary treatment goal, a higher CI IDA dosage, the addition of a P-gp down-regulator such as CsA and others, and in vivo study focusing on tumor samples from patients could all be helpful.

Aged↗
PubMed1997

BEAM chemotherapy and autologous haemopoietic progenitor cell transplantation as front-line therapy for high-risk patients with diffuse large cell lymphoma.

In two consecutive and unselected cohorts of diffuse large cell lymphoma (DLCL) patients with advanced stage disease (IIB or bulk or more) and aged < 60 years, we compared a standard (MACOP-B for 12 weeks, 60 patients) versus a high-dose chemotherapy programme (8 weeks of MACOP-B plus one or two cycles of intensification with mitoxanthrone, dexamethasone, high-dose Ara-C, and finally BEAM chemotherapy with autologous haemopoietic progenitor cell transplantation, 61 patients). 41 patients (68%) in the standard group and 51 (84%) in the high-dose chemotherapy group, achieved a complete remission (CR) or an uncertain complete remission (CRu) (P = 0.0491). With a median follow-up time of 28 months for the high-dose group and 63.5 months for the standard group, the actuarial estimate of event-free survival (EFS) at 2 years demonstrates a significant benefit (70% v 50%, P = 0.03) for patients treated with the intensive regimen. The analysis of subgroups of patients showed that only high-risk patients (two or three risk factors) benefitted from the high-dose chemotherapy programme. Nevertheless, the overall survival does not show a significant difference between the two treatment modalities. The treatment-related morbidity was similar and the mortality rate was 8% in the standard (MACOP-B) group and 3% in the high-dose chemotherapy programme. In conclusion, our results show that high-dose chemotherapy and autologous stem cell transplantation is a safe procedure which should be considered for the front-line treatment of non-Hodgkin lymphoma patients with poor prognostic features.

Adult↗
PubMed1997

Long-term haematological reconstitution following BEAM and autologous transplantation of circulating progenitor cells in non-Hodgkin's lymphoma.

We report on long-term haematological recovery and clinical outcome after high-dose chemotherapy supported by circulating progenitor cells (CPC) transplantation in non-Hodgkin's lymphoma (NHL) patients, and analyse the role of variables which might influence engraftment. 63 consecutive NHL patients were enrolled in this study. Two groups of patients were considered for analysis: the first 34 patients had untreated diffuse large cell lymphoma with unfavourable prognostic factors. A second group of 29 patients underwent transplantation for resistant or relapsing NHL with low, intermediate and high grade histology. All patients received the BEAM conditioning regimen. As already reported in many studies, all patients showed a rapid haematological reconstitution. 43 patients (68%) achieved long-term complete trilineage engraftment within a median of 107 d from CPC transplantation. The neutrophil count was the first parameter reaching complete normalization, and haemoglobin was the last. Failure to meet the trilineage levels was due to lack of platelet recovery and was more frequent in patients transplanted in the setting of salvage protocols. By Kaplan-Meier analysis, the probability of a full reconstitution was 80% in patients to whom transplant was offered as part of a front-line therapy and 50% when transplant was given in the salvage programmes. Multivariate analysis showed that sustained long-term haematological reconstitution was significantly related to younger age, the time taken to achieve short-term reconstitution, and bone marrow involvement.

Adolescent↗
PubMed1996

Factors for rapid and sustained hematopoietic reconstitution by circulating progenitor-cell transplantation in non-Hodgkin's lymphoma.

Circulating progenitor cells (CPCs) mobilized from bone marrow will replace the use of bone marrow transplantation because hematopoietic reconstitution is more rapid using the former technique. We report on early and late recovery of hematopoiesis after CPC transplantation in patients with non-Hodgkin's lymphoma (NHL) and analyze the role of variables possibly influencing engraftment. From December 1992 through September 1995, 57 consecutive NHL patients were enrolled in this study. Patients could be divided into 2 groups: the first comprised 32 patients with untreated diffuse large-cell lymphoma and unfavorable prognostic factors; the second comprised 25 patients with resistant or relapsing NHL of low-and high-grade histology. All patients received high-dose chemotherapy (carmustine, cytarabine, etoposide, and melphalan; BEAM) followed by CPC transplantation. In all, 25 patients were treated with granulocyte colony-stimulating factor (G-CSF) after CPC administration. The time to short-and long-term hematologic engraftment and variables correlating with multilineage long-term reconstitution were examined. The time to bilineage (neutrophils and platelets) hematopoietic reconstitution did not differ in G-CSF-treated and-untreated patients. In contrast, the time taken to reach a neutrophil count of 0.5 x 10(9)/1 and a WBC of 1 x 10(9)/1 was significantly shorter in G-CSF-treated patients. Overall, 33 patients achieved long-term, complete trilineage engraftment after a median of 117 days from CPC transplantation. The leukocyte count was the first parameter to reach full engraftment and hemoglobin was the last. According to Kaplan-Meier analysis, 80% of the patients are projected to reconstitute fully at 12 months after transplantation. Univariate and multivariate analyses showed that sustained, long-term hematopoiesis was significantly related to a younger age, an early bilineage reconstitution, and the quantity of CD34+ cells infused.

Adolescent↗
PubMed1996

G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation of resistant or relapsing acute leukemias.

Peripheral blood progenitor cells (PBPC) were mobilized by G-CSF in normal HLA identical siblings and used for allogeneic transplantation in eight patients with refractory or relapsed acute leukemias. G-CSF administration was well tolerated and no significant side-effects were registered. The number of circulating WBC peaked at day 5 after G-CSF (range: 22.6-74.6 x 10(9)/l) with a median of 65 CD34+ cells/microl (38-155). As a consequence of leukaphereses, platelets progressively decreased, reaching the nadir after the last procedure (84-205 x 10(9)/l). A mean of two aphereses (1-3) were performed between day +4 and +7 during which 10 liters of blood were processed each time by a cell separator. Conditioning regimens were: fractionated total body irradiation (FTBI) plus either HDAra-C (2 g/m2 x 2/day for 6 days) (n=5) or melphalan (110 mg/m2) (n= 1) and busulfan (4 mg/kg/day for 4 days) and melphalan (110 mg/m2) in two patients relapsed after a previous FTBI-based allogeneic or autologous BMT. At transplantation, a median of 6.9 x 10(6) CD34+ cells/kg (4.2-16.5) and 279 x 10(6) CD3+ cells/kg (161-786) were infused. Engraftment of both neutrophils (> or v=1.5 x 10(9)/l) and platelets (> or v=20 x 10(9)/l) was observed in all patients after a median time of 18 days (range: 11-20 and 10-26, respectively). The evaluation of engraftment after transplantation was accomplished by PCR analysis of four hypervariable genomic regions (VNTR) (ApoB, ApoC2, YNZ-22, and MCT 118) which allowed to demonstrate the condition of donor chimaera in all patients after transplantation. As far as the clinical outcome, two patients died of interstitial pneumonitis at day +243 and +69 and two patients died at day +62 and +152 of pulmonary aspergillosis. Four patients remain alive in remission between day +88 and +287 with grade 0-l GVHD. Allogeneic PBPC transplantation is associated with a complete hematologic recovery and despite the infusion of a large amount of mature CD3+ lymphocytes, apparently acute GVHD is not worse than expected after transplantation of bone marrow progenitors.

Adolescent↗
PubMed1995

Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis.

BACKGROUND: Abnormalities in the number and function of platelets may contribute to thromboembolic complications in patients with essential thrombocythemia. We assessed whether maintaining the platelet count below 600,000 per cubic millimeter with hydroxyurea reduces the incidence of thrombosis in patients with essential thrombocythemia and a high risk of thrombosis. METHODS: A total of 114 patients with essential thrombocythemia (77 women and 37 men; median age, 68 years; range, 40 to 85) and a median platelet count of 788,000 per cubic millimeter (range, 533,000 to 1,240,000 per cubic millimeter) were randomly assigned to receive hydroxyurea (56 patients) or no myelosuppressive therapy (58 patients). Ninety-seven (85 percent) were over 60 years old, and 52 (46 percent) had had thrombosis. The two groups were matched for age, sex, and platelet count at randomization. Antiplatelet prophylaxis with aspirin or ticlopidine was not stopped. Follow-up lasted a median of 27 months in both groups. RESULTS: Two patients (3.6 percent) treated with hydroxyurea had thrombotic episodes (one stroke and one myocardial infarction), whereas 14 patients (24 percent) in the control group had thrombotic episodes (one stroke, five transient ischemic attacks, five peripheral arterial occlusions, one deep-vein thrombosis, and two cases of superficial thrombophlebitis). The difference (20.4 percentage points; 95 percent confidence interval, 8.5 to 32 percent) was statistically significant (chi-square with Yates' correction, 8.3; 1 df; P = 0.003). CONCLUSIONS: Hydroxyurea is effective in preventing thrombosis in high-risk patients with essential thrombocythemia.

Adult↗
PubMed1995

Granulocyte colony-stimulating factor following peripheral-blood progenitor-cell transplant in non-Hodgkin's lymphoma.

PURPOSE: To compare the hematologic recovery after high-dose chemotherapy and circulating peripheral-blood progenitor-cell (PBPC) transplant between patients who received recombinant human granulocyte colony-stimulating factor (G-CSF) (treated group) and those who did not (control group). PATIENTS AND METHODS: From December 1992 through June 1994, two sequential and consecutive cohorts of 20 patients each with histologically proven non-Hodgkin's lymphoma (NHL) received high-dose chemotherapy (carmustine [BCNU], cytarabine [Ara-C], etoposide and melphalan [BEAM]) followed by PBPC transplant. The first 20 patients were treated with G-CSF (5 micrograms/kg/d) after PBPC administration. Since the time of platelet and leukocyte recovery in this group was short (< 15 days), with a narrow standard deviation from the mean value, the last 20 patients were not given G-CSF. Hematologic recovery, number of febrile days, rate of documented infections, number of hospital days, duration of gastrointestinal complications, platelet and RBC transfusions, and antibiotic requirements were compared in the two groups. RESULTS: The two groups of patients were comparable according to disease status, histology, stage, bulky disease bone marrow involvement, elevated lactate dehydrogenase (LDH) level, and median number of infused CD34+ cells and colony-forming units granulocyte-macrophage (CFU-GM). The median time to reach 0.5 x 10(9)/L and 1.0 x 10(9)/L neutrophils was 2 days shorter in G-CSF group, but this difference was not statistically significant. The median times to reach 20 x 10(9)/L and 50 x 10(9)/L platelets were, respectively, 10 and 14 days in the G-CSF group and 11 and 16 days in the control group, but again this was not statistically significant. Moreover, when considering clinically relevant end points including the number of documented infections and antibiotic requirements, platelet transfusions, gastrointestinal toxicity, and days of hospitalization, no differences were demonstrated between the two groups. CONCLUSIONS: Provided an optimal dose of circulating progenitors is infused, NHL patients transplanted with PBPC do not benefit by the administration of hematopoietic growth factors.

Adult↗