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1.
Transplant Proc ; 50(7): 2202-2211, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30177137

ABSTRACT

BACKGROUND: High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) remains the mainstay of treatment of eligible patients diagnosed multiple myeloma. The role of clonal plasma cell (CPC) contamination was found as a reason for relapse, but results in terms of survival, progression, and purging were ambiguous. Therefore, the aim of the study was to explore the influence of CPC contamination in the autograft on survival and progression after auto-PBSCT. STUDY DESIGN: The study included 59 patients diagnosed and treated for multiple myeloma in 1998-2004. Cells with coexpression of CD38+++CD138++CD56+ and lacking the expression of CD45, CD19, CD10, CD20, and CD23 were considered CPC in flow cytometry. RESULTS: The risk of death and progression after auto-PBSCT increased significantly by 10% (P < .021) and 8% (P < .034) per 1 × 106/kg of the CPC number, respectively. For CPC number above 2.96 × 106/kg overall survival achieved clinical significance. Two years after auto-PBSCT, the risk of death was independent of CPC number among the patients who survived (P = .70). Analogous conclusions concerned results of progression-free survival at 1 year after auto-PBSCT. CONCLUSIONS: High clonal plasma cell contamination (>2.96 ×1 06/kg; 90th percentile of CPC number) is associated with the worst progression-free survival and overall survival. Therefore purging in vitro might be considered for the patients with the highest CPC contamination. Negative consequences of CPC contamination on the risk of death are observed for only 2 years after auto-PBSCT. Thereafter only those patients who had lower CPC contamination survived.


Subject(s)
Autografts/pathology , Multiple Myeloma/therapy , Peripheral Blood Stem Cell Transplantation/mortality , Peripheral Blood Stem Cells/pathology , Plasma Cells/pathology , Disease Progression , Disease-Free Survival , Female , Flow Cytometry , Humans , Male , Middle Aged , Multiple Myeloma/mortality , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/etiology , Peripheral Blood Stem Cell Transplantation/methods , Transplantation, Autologous
2.
Transplant Proc ; 50(7): 2212-2217, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30177138

ABSTRACT

BACKGROUND: Relapse is the leading cause of treatment failure for myeloid malignancies treated with allogeneic hematopoietic stem cell transplantation. Treatment options are very limited and use of azacitidine is one of the available options. METHODS: This was a retrospective, single-institution study. Of 28 evaluated patients, 18 were males, and the median age was 60 years (range, 15-78). There were 15 patients with acute myeloid leukemia, 8 with myelodysplastic syndrome, 4 with chronic myelomonocytic leukemia, and 1 with primary myelofibrosis. Ten patients received azacitidine for overt relapse, 14 received it as a preemptive therapy, and 4 others received it as maintenance treatment after allo-hematopoietic cell transplant (HSCT). Eleven patients received a donor lymphocyte infusion (DLI). RESULTS: The patients received median 5 (1-9) cycles of azacitidine in preemptive and maintenance therapy and median 2.5 (1-9) cycles in patients with relapse. Thirty-nine percent of patients received DLIs. Median overall survival was 6.1 months (95% CI, 0.7-13) for relapse therapy vs 21.2 months (95% CI, 8.4-inf) for preemptive therapy. Among patients treated for relapse, 30% achieved temporary disease control and underwent the second allo-HSCT. A complete, cytogenetic remission was achieved in 50% of patients and stable minimal residual disease in 14% of patients in a group with preemptive therapy. Toxicity was considerable; neutropenia (71%), anemia (14%), thrombocytopenia (36%), and serious infections (36%) were observed in the preemptive setting. CONCLUSIONS: These data support the notion that azacitidine is best used as a preemptive therapy against relapse for patients after allo-HSCT performed for myeloid malignancy. Applying azacitidine as therapy for ongoing relapse after allo-HSCT may lead to stable disease and allow for better performance of the second allo-HSCT.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Bone Marrow Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Myeloproliferative Disorders/therapy , Neoplasm Recurrence, Local/drug therapy , Adolescent , Adult , Aged , Female , Humans , Induction Chemotherapy , Leukemia, Myeloid, Acute/therapy , Leukemia, Myelomonocytic, Chronic/therapy , Male , Middle Aged , Myelodysplastic Syndromes/therapy , Neoplasm Recurrence, Local/etiology , Neoplasm, Residual , Primary Myelofibrosis/therapy , Retrospective Studies , Transplantation, Homologous , Young Adult
3.
Transplant Proc ; 50(7): 2218-2222, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30177139

ABSTRACT

BACKGROUND: There are only a few cases of pericarditis complications following allogeneic bone marrow transplantation described in the literature and there are no data available on the risk and frequency of this condition. The aim of this study was to assess the frequency of exudative pericarditis complicating chronic graft-vs-host disease in allogeneic hematopoietic cell transplant recipients. METHODS: Retrospective analysis involved a group of 105 patients of the Outpatient Transplantation Service of the Department of Hematology, Medical University of Warsaw, who received transplants in the years 2010-2016 and were evaluated for the years 2014-2016. In this group, 50 patients suffered from chronic graft-vs-host disease (cGVHD), including 24 with moderate or severe disease. Cardiology parameters evaluated included electrocardiography, echocardiography, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and systematic clinical follow-up. RESULTS: Pericarditis was diagnosed in 6 patients (aged 20-56 years) within 4 to 23 months after allogenic hematopoietic stem cell transplantation. All patients suffered from severe cGVHD with involvement of at least 2 organs but none had earlier history of heart disease. All patients had elevated NT-proBNP and demonstrated signs of heart insufficiency grade II or III according to the New York Heart Association. There were no major changes in electrocardiogram. Only 1 patient improved following glucocorticosteroids as monotherapy, while others required complex approaches including tacrolimus plus sirolimus, rituximab, and extracorporeal photopheresis. CONCLUSION: Late pericarditis may occur in up to 5% of allogenic hematopoietic stem cell transplantation survivors, primarily affecting patients with moderate and severe grade cGVHD. It requires escalation of immunosuppressive treatment but usually has favorable outcome. Early diagnosis may be achieved by systematic NT-proBNP testing and periodic echocardiograph evaluation.


Subject(s)
Bone Marrow Transplantation/adverse effects , Graft vs Host Disease/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Pericarditis/etiology , Adult , Chronic Disease , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Pericarditis/therapy , Photopheresis , Retrospective Studies , Risk Factors , Rituximab/therapeutic use , Sirolimus/therapeutic use , Tacrolimus/therapeutic use , Young Adult
4.
Transplant Proc ; 48(5): 1802-5, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27496495

ABSTRACT

BACKGROUND: Relapse of primary hematologic disease constitutes an important reason for failure of allogeneic hematopoietic stem cell transplantation (alloHSCT). There are very few treatment modalities for this indications. Therefore, there is a need for novel effective therapies and even more for the prevention of relapse. There are scarce data that azacitidine can be used for these purposes. METHODS: At the Polish Adult Leukemia Group, we retrospectively analyzed the results of azacitidine treatment after alloHSCT. Relapsing patients, patients with minimal residual disease/mixed chimerism, and patients in complete remission with high risk of relapse were analyzed separately. There were 17 patients, 6 with myelodysplastic syndrome, 11 with acute myeloid leukemia, 8 male, and overall median age of 56 years (range, 15-78); 7 patients received donor lymphocyte infusion (DLI). RESULTS: Patients treated because of relapse received a median of 3 (range, 1-6) cycles of azacitidine, patients receiving preemptive treatment received a median of 4 cycles (range, 2-6), and those on maintenance received a median of 5 cycles (range, 3-5). Toxicity was considerable, especially in relapse-neutropenia (67%), anemia (67%), thrombocytopenia (100%), serious infections (78%)-and preemptive settings. Median overall survival of patients treated for relapse reached 6.8 months (95% confidence interval [CI], 0.7-∞), with better survival observed in patients with temporary disease control (7.7 vs 4.7 mo) and without previous exposure to azacitidine (7.7 vs 3.4 mo). One-year overall survival reached 75% (95% CI, 13%-96%) for preemptive and 50% (95% CI, 0%-91%) for maintenance treatment. DLI did not aggravate graft-versus-host disease. CONCLUSIONS: Effectiveness of azacitidine in relapsing patients is disappointing. Azacitidine seems to be promising in preemptive and maintenance settings. Toxicity is considerable. Further research is needed.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adolescent , Adult , Aged , Female , Humans , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/surgery , Male , Middle Aged , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/surgery , Neoplasm Recurrence, Local/mortality , Poland , Retrospective Studies , Transplantation, Homologous/adverse effects , Young Adult
5.
Transplant Proc ; 46(8): 2877-81, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25380940

ABSTRACT

BACKGROUND: Systemic immunoglobulin light-chain amyloidosis (AL) is a plasma cell dyscrasia resulting in multisystem organ failure and death. Autologous hematopoietic stem-cell transplantation (ASCT) has been widely used to treat patients with AL. However, treatment-related mortality remains high and reported series are subject to selection bias. METHODS: To define the role of patient selection in stem cell transplantation, we evaluated 24 consecutive AL patients transplanted at our center. RESULTS: Complete hematologic response was achieved in all 20 patients surviving >100 days posttransplantation. The 1-year overall survival (OS) rate after ASCT was 78.5%. The 5- and 10-year progression-free and OS rates were 57% and 47%, respectively. Treatment-related deaths owing to cardiovascular problems occurred in 16% of cases. CONCLUSION: ASCT for AL amyloidosis can be safely performed in experienced transplantation centers, and increased risk is associated mainly with cardiovascular system involvement.


Subject(s)
Amyloidosis/drug therapy , Amyloidosis/surgery , Hematopoietic Stem Cell Transplantation , Melphalan/administration & dosage , Myeloablative Agonists/administration & dosage , Adult , Aged , Female , Hematopoietic Stem Cell Transplantation/mortality , Humans , Immunoglobulin Light-chain Amyloidosis , Male , Melphalan/therapeutic use , Middle Aged , Patient Selection , Retrospective Studies , Survival Analysis , Transplantation, Autologous
6.
Adv Med Sci ; 51 Suppl 1: 66-8, 2006.
Article in English | MEDLINE | ID: mdl-17460832

ABSTRACT

PURPOSE: The aim of this study was to assess the state of oral mucosa in a patient after allo-PBSCT who has received palifermin, a recombinant human keratinocyte growth factor. MATERIAL AND METHODS: A 19-year-old male was treated in the Department of Haematology of the Medical University in Warsaw due to the AML. Conditional chemotherapy was applied, according to the BuCy 4 + ATG regimen and allogeneic haematopoietic cells transplantation from an unrelated donor. He was receiving palifermin intravenously for 3 consecutive days immediately before the initiation of conditioning therapy and after allogeneic PBSCT. On day +3 the oral mucous membrane was pale and swollen, with linea alba visible on cheeks. Superficial glossitis and viral pharyngitis were noted. Beginning with day +5/+6 proliferative gingivitis was observed. On day +9 gingival contour was altered and the gingiva covered nearly completely tooth crowns of all teeth. The gingiva were whitened, as if covered by thick epithelium. Slight gingival hyperplasia was still observed on day +24. Since day +4/+5 skin rash coexisted, spreading over hairy head skin, face, dorsum and chest. Disseminated papulopustular (acne-like) lesions were observed, some of them related to the hair follicles. Skin changes were present till day +15. CONCLUSIONS: Palifermin is an efficient pharmaceutical in mucositis prevention in patients after allogeneic PBSC transplantation. Transient complication of hyperplastic gingivitis with a concomitant skin eczema of a papulopustular nature arose.


Subject(s)
Eczema/chemically induced , Fibroblast Growth Factor 7/adverse effects , Gingivitis/chemically induced , Mucositis/prevention & control , Recombinant Proteins/adverse effects , Adult , Eczema/pathology , Fibroblast Growth Factor 7/therapeutic use , Gingivitis/pathology , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/surgery , Male , Mouth Mucosa/pathology , Recombinant Proteins/therapeutic use , Skin/pathology
7.
Neoplasma ; 52(3): 267-72, 2005.
Article in English | MEDLINE | ID: mdl-15875091

ABSTRACT

Histological, clinical and immunohistochemical analysis of 6 cases of primary liver lymphomas (PLL) are presented. PLL represents 4.3% of primary malignant liver tumors diagnosed in our department. The patients were relatively young people, who despite the presence of a large tumor, were in good general health status. There were no signs of scirrhosis, and cancer markers were normal. All lymphomas were CD20, CD79a, BAX positive, CD3, CD30, EMA, CD10, CD5, CD59, c-myc, Bcl2, EBV(LMP), CK negative. The proliferation index (Ki67) was high, ranging from 50-100%. In two cases positive staining for Bcl6 and in another one for cyclin D1 was obtained. The major histological type of the tumor was diffuse large B-cell lymphoma. Positive immunohistochemical results with BAX and the lack of Bcl2, c-myc and CD59 are associated with better prognosis. We have not confirmed the value of Bcl6 and CD10 stains as a predictor of poor outcome. Despite clinically advanced stage at the time of diagnosis, if treated appropriately, the primary lymphoma of the liver has relatively good prognosis (five of our patients are alive).


Subject(s)
Liver Neoplasms/diagnosis , Liver Neoplasms/surgery , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/surgery , Adolescent , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , CD59 Antigens/metabolism , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Immunohistochemistry , Liver Neoplasms/metabolism , Lymphoma, Large B-Cell, Diffuse/metabolism , Male , Prognosis , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Stem Cell Transplantation , bcl-2-Associated X Protein
8.
Ann Hematol ; 83(4): 225-31, 2004 Apr.
Article in English | MEDLINE | ID: mdl-14648030

ABSTRACT

This is a retrospective, multicenter study to evaluate biological features and outcome of elderly patients diagnosed with acute lymphoblastic leukemia (ALL) during the last 10 years in ten hematological centers in Poland. Eighty-seven patients aged 60 years or older were studied. To our knowledge, this is one of the largest group of elderly patients with ALL evaluated. We have not observed differences in immunological subtypes and Ph chromosome incidence as compared with younger adult ALL presented in the literature. Induction chemotherapy was administered in 75 patients. We observed complete remission (CR) in 34 (45%, 95% CI: 33-56%) patients. Induction death occurred in 11 (15%) patients. Thirty patients (40%) showed primary resistance to chemotherapy. Median overall survival (OS) of all patients was 150 days. Median disease-free survival (DFS) of responding patients was 180 days. We observed four long-term survivors (DFS longer than 3 years) in our group of patients. Factors influencing OS were CR achievement, female gender, and WBC below 30 x 10(9)/l. Male gender was the only prognostic factor negatively affecting probability to achieve CR. We have not observed any differences in either biology or outcome between patients aged 60-69 years and those aged more than 70 years. ALL of the elderly is a rare disease with poor prognosis. Further clinical trials evaluating the disease features, outcome, and new therapeutic approaches are warranted.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Aged , Aged, 80 and over , Female , Humans , Immunophenotyping , Leukocyte Count , Male , Middle Aged , Poland , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prognosis , Remission Induction , Retrospective Studies , Sex Factors , Survival Analysis , Treatment Outcome
9.
Transplant Proc ; 35(6): 2352-4, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14529939

ABSTRACT

Approximately one third of multiple myeloma patients (below 60 years) are diagnosed either in advanced disease or with significant comorbidities. Many other patients referred to transplant centers have already been heavily pretreated with multiple courses of various conventional chemotherapies. These patients are frequently in bad or even grave clinical condition; they are unlikely to survive standard high-dose melphalan (200 mg/m(3)) chemotherapy and autologous hematopoietic stem cell transplantation. Palumbo et al reported a protocol for elderly patients that utilized reduced conditioning (melphalan 100 mg/m(2) three times at 2-month intervals, each time supported by autologous hematopoietic rescue). We have used this protocol as a start to develop a method to induce a remission in the aforementioned subgroup of myeloma patients. Patients with stage III disease and WHO performance status 2 or higher are treated with one or two cycles of cyclophosphamide (2 to 4 g/m(2)) and undergo peripheral blood stem cells collection. Subsequently, they are treated with three to four doses of melphalan (100 mg/m(2)) at 8- to 12-weeks intervals each time supported by infusion of peripheral blood stem cells. To date 13 patients have been entered into the protocol. With one exception of transiently stable disease, the remaining patients obtained at least partial remission and three, complete remission. The compliance was good and better with each subsequent course. For half of the patients the problem was a short duration of response. This method when developed may offer a new treatment alternative for a subgroup of high-risk multiple myeloma patients.


Subject(s)
Melphalan/therapeutic use , Multiple Myeloma/therapy , Stem Cell Transplantation/methods , Adult , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Dexamethasone/administration & dosage , Disease Progression , Disease-Free Survival , Doxorubicin/administration & dosage , Humans , Immunoglobulins/urine , Middle Aged , Multiple Myeloma/immunology , Transplantation, Autologous , Treatment Outcome , Vincristine/administration & dosage
10.
Pol Arch Med Wewn ; 105(3): 225-9, 2001 Mar.
Article in Polish | MEDLINE | ID: mdl-11680267

ABSTRACT

Serum concentration of thrombopoietin (Tpo) and interleukin 6 (IL-6) were measured in 37 patients with thrombocythaemia and in the healthy volunteers. 27 patient were classified as persons with chronic myeloproliferative disorder (MPD) and 10 as with reactive thrombocythaemia (RT). The mean plasma Tpo concentration did not differ statistically between the groups. IL-6 levels were significantly higher in patients with RT than in patients with MPD and controls. The mean plasma IL-6 levels was lowest in patients with essential thrombocythaemia. In conclusion, serum IL-6 concentration may be useful in the differential diagnosis of thrombocytosis.


Subject(s)
Interleukin-6/blood , Thrombocytosis/blood , Thrombocytosis/diagnosis , Thrombopoietin/blood , Adolescent , Adult , Aged , Aged, 80 and over , Chronic Disease , Female , Humans , Male , Middle Aged , Severity of Illness Index
11.
Leukemia ; 15(10): 1510-6, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11587207

ABSTRACT

The objective of the study was to determine the effectiveness and the toxicity of a combined chemotherapy consisting of cladribine (2-CdA), mitoxantrone and cyclophosphamide (CMC regimen) in the treatment of previously untreated B cell chronic lymphocytic leukemia (B-CLL). From August 1998 to December 2000 2-CdA was administered at a dosage of 0.12 mg/kg for 3 (CMC3) or 5 (CMC5) consecutive days, mitoxantrone at 10 mg/m2 on day 1 and cyclophosphamide at 650 mg/m2 on day 1 to 62 patients with advanced or progressive B-CLL. The cycles were repeated at 4 week intervals or longer if severe myelosuppression occurred. Twenty patients received CMC5 and 42 patients CMC3. Within the analyzed group an overall response (OR) rate (CR+PR) of 64.5% (95% CI: 52.7-76.3%) was reported, including 29.0% CR. There was no difference in the CR rate between the patients treated with CMC5 (30%) and CMC3 (28.6%) (P = 0.9), nor in the OR rate (55.0% and 69.0%, respectively, P = 0.3). Residual disease was identified in seven out of 18 (38.9%) patients who were in CR, including two treated with CMC5 and five treated with CMC3 protocols. CMC-induced grade III or IV thrombocytopenia occurred in 12 (19.4%) of patients, including four (20%) CMC5-treated and eight (19%) CMC3-treated patients (P= 0.8). Neutropenia grade III or IV was observed in seven (35%) and 11 (26.2%) patients, respectively (P = 0.8). Severe infections, including pneumonia and sepsis, occurred more frequently after CMC5 (11 patients, 55.0%) than CMC3 (10 patients, 28.6%) (P = 0.03) Fourteen patients died, including six treated with CMC5 and eight treated with CMC3 (30% and 19%, respectively). Infections were the cause of death in nine patients, including four in the CMC5 group and five in the CMC3 group. In conclusion, our results indicate that the CMC programme is an active combined regimen in previously untreated B-CLL patients; its efficiency seems to be similar to that observed earlier in B-CLL patients treated with 2-CdA as a single agent. However, toxicity, especially after CMC5 administration, is significant. Therefore, we recommend the CMC3 but not the CMC5 programme for further evaluation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/toxicity , Cause of Death , Cladribine/administration & dosage , Cladribine/toxicity , Cohort Studies , Cyclophosphamide/administration & dosage , Cyclophosphamide/toxicity , Female , Humans , Infections/chemically induced , Male , Middle Aged , Mitoxantrone/administration & dosage , Mitoxantrone/toxicity , Pancytopenia/chemically induced , Treatment Outcome , Vomiting/chemically induced
12.
Med Oncol ; 18(2): 141-8, 2001.
Article in English | MEDLINE | ID: mdl-11778760

ABSTRACT

The objective of this multiinstitutional study was to evaluate the safety and efficacy of rituximab at standard four weekly doses in patients with recurrent indolent lymphoma. Thirty-eight patients entered into this study, 63% had follicular lymphoma and 61% had an IPI score of 2 or more. Median disease duration was 3 yr, median number of prior treatments was three, and 66% of patients responded to the immediate past treatment with a median remission duration of 3 mo. A total of 158 antibody doses were given, including two patients who received two courses of four infusions each. One patient developed acute respiratory failure after the second dose and required assisted ventilation. There was no immediate relationship to the antibody infusion and no evidence of infection. This complication resolved and the patient successfully completed the full course of the antibody treatment. Another patient discontinued therapy after the second dose owing to intolerable fever and painful erythema. Sixty percent of the first, and 20% of subsequent rituximab infusions were associated with infusion-related reactions including mild fever, chills, and occasional skin eruptions. Complete and partial responses were achieved in 24% and 35% of 34 evaluable patients, respectively, for an overall response rate of 59%. The median time to progression/relapse in responding patients was 16 mo (95% CI, 6.4, 25.6) compared with a median of 3 mo duration of response to the immediate previous therapy in these patients. Longer response duration post rituximab monotherapy than with previous treatment in this series of heavily pretreated patients suggests a major role for the antibody in the therapy of patients with indolent lymphoma.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Lymphoma, Follicular/drug therapy , Adult , Aged , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Agents/adverse effects , Disease Progression , Disease-Free Survival , Female , Humans , Infusions, Intravenous , Lymphoma, Follicular/pathology , Male , Middle Aged , Recurrence , Respiratory Insufficiency/chemically induced , Rituximab , Treatment Outcome
13.
Blood ; 96(8): 2723-9, 2000 Oct 15.
Article in English | MEDLINE | ID: mdl-11023504

ABSTRACT

The efficacy and toxicity of cladribine (2-CdA) + prednisone (P) versus chlorambucil (Chl) + P were compared in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia (CLL) in a randomized, multicenter prospective trial. Eligible patients were assigned to either 2-CdA 0.12 mg/kg per day in 2-hour infusions and P 30 mg/m(2) per day for 5 consecutive days or Chl 12 mg/m(2) per day and P 30 mg/m(2) per day for 7 consecutive days. Three courses were administered at 28-day intervals or longer if myelosuppression developed. The therapy was finished if complete response (CR) was achieved. Of 229 available patients 126 received 2-CdA+P and 103 received Chl+P as a first-line treatment. CR and overall response rates were significantly higher in the patients treated with 2-CdA+P (47% and 87%, respectively) than in the patients treated with Chl+P (12% and 57%, respectively) (P = .001). Progression-free survival was significantly longer in the 2-CdA-treated group (P = .01), but event-free survival was not statistically different. Thirteen percent of patients were refractory to 2-CdA+P and 43% to Chl+P (P = .001). Drug-induced neutropenia was more frequently observed during 2-CdA+P (23%) than Chl+P therapy (11%) (P = .02), but thrombocytopenia occurred with similar frequency in both groups (36% and 27%, respectively). Infections were seen more frequently in the 2-CdA+P-treated group (56%) than in the Chl+P-treated group (40%; P = .02). Death rates have so far been similar in patients treated with 2-CdA (20%) and with Chl (17%). The probability of overall survival calculated from Kaplan-Meier curves at 24 months was also similar for both groups (78% and 82%, respectively). (Blood. 2000;96:2723-2729)


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chlorambucil/administration & dosage , Chlorambucil/adverse effects , Cladribine/administration & dosage , Cladribine/adverse effects , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Incidence , Infections/epidemiology , Infections/etiology , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Life Tables , Male , Middle Aged , Neutropenia/chemically induced , Neutropenia/epidemiology , Poland/epidemiology , Prednisone/administration & dosage , Prednisone/adverse effects , Prospective Studies , Remission Induction , Survival Rate , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Treatment Outcome
14.
Br J Haematol ; 108(2): 357-68, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10691866

ABSTRACT

Between January 1992 and January 1999, we treated 378 B-chronic lymphocytic leukaemia (CLL) patients with cladribine (2-CdA), and 255 of the patients were also treated with prednisone. A total of 194 patients were previously untreated, and 184 had relapsed or refractory disease after previous other therapy. Complete response (CR) was obtained in 111 (29.4%) and partial response (PR) in 138 (36.5%) patients, giving an overall response (OR) rate of 65.9%. CR and OR were achieved more frequently in patients in whom 2-CdA was a first-line treatment (45.4% and 82.5% respectively) than in the pretreated group (12.5% and 48.4% respectively) (P < 0.0001). The median duration of OR for previously untreated patients was 14.7 months and for pretreated patients 13.5 months (P = 0.09). The median survival evaluated from the beginning of 2-CdA treatment was shorter in the pretreated group (16.3 months) than in the untreated group (19.4 months) (P < 0.0001). A total of 117 (63.9%) patients died in the pretreated group and 63 (32.6%) in the untreated group. In pretreated patients, 2-CdA + prednisone (P) and 2-CdA alone resulted in similar OR (51.0% and 45.0% respectively; P = 0.4). In contrast, in untreated patients, 2-CdA + P produced a higher OR (85.4%) than 2-CdA alone (72.1%) (P = 0.04). Infections and fever of unknown origin, observed in 91 (49.4%) pretreated and 74 (38.1%) untreated patients (P = 0.03), were the most frequent toxic effects. Our results indicate that 2-CdA is an effective, relatively well-tolerated drug, especially in previously untreated CLL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , 2-Chloroadenosine/administration & dosage , 2-Chloroadenosine/analogs & derivatives , Adult , Aged , Aged, 80 and over , Cladribine/administration & dosage , Deoxyadenosines/administration & dosage , Female , Humans , Male , Middle Aged , Prednisone/administration & dosage , Prospective Studies , Survival Analysis
15.
Eur J Haematol ; 62(1): 49-56, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9918312

ABSTRACT

Between January 1991 and December 1997, 103 patients, 97 with typical hairy cell leukemia (HCL) and 6 with HCL-variant (HCL-V) were treated with 2-chlorodeoxyadenosine (2-CdA) given as 2-h infusion for 5 consecutive d at a daily dose 0.12 mg/kg. To our knowledge this is the largest cohort of HCL patients treated with this type of regimen. Median follow-up amounted to 36 months. Fifty-six of 97 patients with typical HCL were newly diagnosed and 41 were relapsed after previous treatment. Splenectomy as a first-line therapy was performed in 23 patients and 18 remaining patients received prednisone, chlorambucil or interferon-alpha (IFN-alpha) alone or in combinations. Seventy-five (77.3%) patients entered CR and 18 (18.6%) achieved PR, giving an overall response rate of 95.9%. The mean time of first CR duration amounting to 32 months (range 3-72) did not correlate to the number of 2-CdA cycles. 2-CdA was equally effective in treatment of newly diagnosed patients and patients who relapsed after previous therapeutic procedures. Relapse of the disease occurred in 20 of 75 patients who achieved CR after 2-CdA and was usually manifested by very discrete changes in peripheral blood counts (neutropenia and/or relative lymphocytosis). The mean progression-free survival (PFS) time in this group was 37.4 (range 10-66) months. Ten of 20 relapsed patients were retreated with 2-CdA given an identical course to the first one. Seven patients entered second CR lasting 19+ (range 8-47) months and 3 experienced PR. This confirms the previous observations that 2-CdA gives no resistance to leukemic clone. Ten remaining patients have not required retreatment so far and remain in a good clinical and hematological state. The results of HCL-V treatment with 2-CdA were poor. Only 2 patients achieved PR and 4 patients did not respond to this drug. Seven patients (5 with typical HCL and 2 with HCL-V) died, 3 of causes unrelated to the disease. Second neoplasms were noted in 5 patients. 2-CdA-related side effects resulted mainly from myelosuppression and infectious complications. In conclusion we confirm the effectiveness of 2-CdA in inducing CR in patients with typical HCL, but this drug is unable to completely eradicate the leukemic clone which results in the relapse of the disease. The real incidence of the relapse rate may be underestimated unless bone marrow biopsy is performed. The results of our study indicate that a 2-h infusion of 2-CdA in HCL patients is at least as effective as a 24-h infusion but more convenient to the patients, and may be given on an outpatient basis.


Subject(s)
Antineoplastic Agents/therapeutic use , Cladribine/therapeutic use , Leukemia, Hairy Cell/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/toxicity , Cladribine/administration & dosage , Cladribine/toxicity , Cohort Studies , Female , Humans , Leukemia, Hairy Cell/mortality , Male , Middle Aged , Neoplasms, Second Primary/secondary , Neutropenia/etiology , Poland , Survival Rate , Thrombocytopenia/etiology , Time Factors , Treatment Outcome
16.
Pol Merkur Lekarski ; 4(23): 262-4, 1998 May.
Article in Polish | MEDLINE | ID: mdl-9825658

ABSTRACT

Clinical symptoms and haematological disorders in patients suffering from lymphoplasmatic/lymphoplasmocytoidal lymphoma were presented, 82 patients were examined (median age of 63), all of the in clinical stage IV (ANN Arbor scale). In all of the patients bone marrow was invaded. The most common symptom was enlargement of peripheral lymph nodes (86%) less often abdominal ones (21%). Splenomegalia was found in 55% and hepatomegalia in 49% of patients 35% of patients had anaemia and 38% thrombocytopenia. Close to 1/3 of patients dermatoses were found, in most cases allergic ones. In 7% another cancer was found.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Adult , Aged , Aged, 80 and over , Anemia/diagnosis , Female , Humans , Lymph Nodes , Male , Middle Aged , Retrospective Studies , Thrombocytopenia/diagnosis
17.
Pol Arch Med Wewn ; 98(8): 117-21, 1997 Aug.
Article in Polish | MEDLINE | ID: mdl-9508664

ABSTRACT

Secondary thrombocytosis appears in patients with various neoplastic and autoaggressive diseases and infections. Thrombocytosis occurrence among 358 patients with NHL and 46 with HD treated at the Department of Haematology of CMKP (Postgraduate Training Centre) and Warsaw Medical School in 1986-1993 is here presented. The 11 patients (3%) among the ones with NHL and the 11 (24%) with HD showed thrombocytosis. Much more frequently the increased thrombocyte count could have been found in patients with low grade T-cell lymphomas (14%) and in patients with Hodgkin's disease. The patients with chronic B-cell lymphocytic leukemia (1%) showed thrombocytosis in very few cases. Thrombocyte count in patients with NHL was not high (mean-596.0 x 10(9)/L median-558.0 x 10(9)/L) which was similar as in those with HD (mean-601.0 x 10(9)/L median-558.0 x 10(9)/L).


Subject(s)
Hodgkin Disease/complications , Lymphoma, Non-Hodgkin/complications , Thrombocytosis/etiology , Adult , Aged , Female , Hodgkin Disease/blood , Humans , Leukemia, B-Cell/blood , Leukemia, B-Cell/complications , Lymphoma, Non-Hodgkin/blood , Lymphoma, T-Cell/blood , Lymphoma, T-Cell/complications , Male , Middle Aged , Platelet Count , Thrombocytosis/blood
18.
Leuk Lymphoma ; 26(1-2): 99-105, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9250793

ABSTRACT

The purpose of our study was to determine the efficacy of 2-chlorodeoxyadenosine (2-CdA) administered in 2-hour intravenous infusions in previously treated patients with low grade non-Hodgkin's lymphoma (LGNHL). We treated 94 LGNHL patients with 2-CdA at a dosage of 0.12 mg/kg/24h in 2-hour intravenous infusion for 5 consecutive days. The treatment consisted of from 1 to 7 courses (median 3), repeated usually at monthly intervals. All patients were refractory to or relapsed after standard chemotherapy. Of these 94 patients 78 (83%) had clinical stage IV of the disease. Complete response (CR) was obtained in 12 (12.8%) and partial response (PR) in 36 (38.3%) giving an overall response rate of 51.1%. In 12 (12.8%) grade 4 thrombocytopenia with haemorrhagic diathesis was noted, grade 4 neutropenia was observed in 12 (12.8%) and infections complicated the course of treatment in 38 (40.4%) patients. 2-CdA treatment was the cause of death of 3 patients. The results of our study show that 2-CdA given in 2-hour infusions is an effective agent in advanced, heavily pretreated patients with LGNHL.


Subject(s)
Antineoplastic Agents/therapeutic use , Cladribine/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Adult , Aged , Antineoplastic Agents/adverse effects , Cladribine/adverse effects , Female , Humans , Infusions, Intravenous , Lymphoma, Non-Hodgkin/pathology , Male , Middle Aged , Neoplasm Staging , Retreatment
19.
Pol Merkur Lekarski ; 1(6): 424-7, 1996 Dec.
Article in Polish | MEDLINE | ID: mdl-9273240

ABSTRACT

Non-granuloma lymphomas (non-Hodgkin lymphoma) are neoplasms from lymphoid cell line. In this article the classification of non-granuloma lymphomas is presented according to actual knowledge.


Subject(s)
Lymphoma, Non-Hodgkin/classification , Humans
20.
Leuk Lymphoma ; 22(5-6): 509-14, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8882965

ABSTRACT

The purpose of our study was to determine the effectiveness of 2-CdA in 2-hour intravenous infusions in the treatment of B-CLL. One hundred and ten patients with B-CLL received 1 to 10 courses of 2-CdA (median 2.5) at a dosage of 0.12 mg/kg daily for 5 consecutive days. Eighteen of them were untreated and 92 relapsed or became refractory to previous therapeutic modalities. Complete remission (CR) was achieved in 8 (7.3%) and partial remission (PR) in 35 patients (31.8%) giving an overall response rate of 39.1%. In 3 patients, cross-resistance to fludarabine was noticed. Toxic effects of 2-CdA were more frequently observed in previously treated patients. Hemorrhagic complications due to drug-induced thrombocytopenia were noticed in 25 (22.7%) and severe infections including sepsis in 14 (12.7%) patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Cladribine/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Cladribine/administration & dosage , Cladribine/adverse effects , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Infusions, Intravenous , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Middle Aged , Neoplasm Staging , Recurrence , Vidarabine/analogs & derivatives , Vidarabine/therapeutic use
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