Unsuccessful association of zidovudine and interferon alpha for acute adult T-cell leukemia lymphoma.
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Adult↗
Biomedical subjects
V Leblond
Publications and source records attributed to V Leblond.
Intensive chemotherapy with hematopoietic cell transplantation after ESHAP therapy for relapsed or refractory non-Hodgkin's lymphoma. Results of a single-centre study of 65 patients.
This study was designed to assess the results of protracted courses of ESHAP (etoposide, cytarabine, cisplatin, methylprednisolone) therapy followed by intensive chemotherapy and hematopoietic cell transplantation (IC+HCT) for relapsed or refractory non-Hodgkin's lymphoma (NHL). Treatment consisted of 3 cycles of ESHAP; responsive patients (pts) then received 3 more cycles, and IC+HCT was used for pts in maintained partial (PR) or complete (CR) remission after the sixth ESHAP. Sixty-five pts entered the study. At enrollment, 27 pts had bone marrow (BM) and/or central nervous system (CNS) lymphomatous infiltration. Disease status was primary refractory lymphoma in 41 pts (63 %), and relapse in 24 pts (37 %). Results showed that two pts were not evaluable for the therapeutic response because of early treatment-related death. Thirty-nine (62 %) pts entered PR or CR after 3 cycles of ESHAP. Eleven pts subsequently had disease progression. Twenty-eight pts were in persistent CR or PR after 6 cycles of ESHAP. Refractory pts did not show a different response rate to relapsing pts (chi2= 1.73). Five pts were excluded from IC+HCT because of an inadequate graft or treatment-related toxicity. Twenty-three (35 %) pts completed the procedure. Five pts (22 %) relapsed after IC+HCT. The overall survival rate of the 39 responsive pts is 45 % at 60 months, with a median survival time of 30 months. Median survival among the 35 pts in whom second-line chemotherapy failed is 7.1 months, with a 4-year survival rate of 3 %. Despite the poor prognostic features of this group, 45% of pts responding to the first 3 cycles of chemotherapy are in prolonged remission, suggesting that rather than to transplant after just 2 cycles of salvage therapy, pursuing second-line chemotherapy may better discriminate between patients more likely to benefit from a subsequent transplant.
Adolescent↗
[Bullous hemorrhagic colitis revealing type AL amyloidosis].
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Amyloidosis↗
Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party.
To determine the incidence and outcome of hepatic veno-occlusive disease (VOD) after blood or marrow transplantation (BMT), we prospectively evaluated all consecutive patients receiving a BMT during a 6-month period in participating EBMT centers. All of them were evaluated for occurrence of VOD according to previously defined clinical criteria. The clinical course, outcome, value of prophylactic and therapeutic interventions, and the influence of previously described risk factors were analyzed. During the study period, 1,652 BMT were performed in 73 centers. VOD was diagnosed in 87 patients (5.3%; 95% confidence interval [CI], 4.2% to 6.4%). Fifty-six of 631 allogeneic BMT (8.9%) and 31 of 1,010 autologous BMT (3.1%) developed this complication (P <.0001). VOD was classified as mild in 7 (8%), moderate in 56 (64.4%), and severe in 24 (27.6%) cases. Sixteen patients died of VOD (corresponding to 1% of the whole series, 18.4% of VOD patients, and 66.7% of severe VOD). The use of unfractionated heparin did not significantly decrease the incidence of VOD. Independent variables associated with an increased risk of VOD were allogeneic BMT (relative risk [RR], 2.8; P <.001), pre-BMT elevation of serum aspartate aminotransferase (RR, 2.4; P =.001), high-dose cytoreductive therapy (RR, 2.3; P =.003), Karnofsky performance score less than 90% (RR, 2.7; P =.006), and prior abdominal radiation (RR, 2.9; P =.03). In conclusion, this prospective study shows that (1) the incidence of VOD is lower than that reported in smaller studies from single centers, (2) about one fourth of cases of VOD progress to severe disease, (3) main risk factors have a major impact on incidence of VOD, and (4) the use of prophylactic unfractionated heparin does not seem to reduce the incidence of VOD.
Adult↗
High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial.
Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the late group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWiSTT) were 27.8 months (95% confidence interval [CI]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exceeding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of chemotherapy.
Adult↗
Anti-B-cell monoclonal antibody treatment of severe posttransplant B-lymphoproliferative disorder: prognostic factors and long-term outcome.
B-lymphoproliferative disorder (BLPD) is a rare but severe complication of organ and bone marrow transplantation (BMT). Profound cytotoxic T-cell deficiency is thought to allow the outgrowth of Epstein-Barr virus-transformed B cells. When possible, reduction of immunosuppressive treatment or surgery for localized disease may cure BLPD. Therapeutic approaches using chemotherapy or antiviral drugs have limited effects on survival. Adoptive immunotherapy with donor T-cell infusions has given promising results in BMT recipients. We previously reported that administration of two monoclonal anti-B-cell antibodies (anti-CD21 and anti-CD24) could contribute to the control of oligoclonal BLPD. Here we report the long-term results of treatment with these monoclonal anti-B-cell antibodies for cases of severe BLPD. In an open multicenter trial, 58 patients in whom aggressive B-cell lymphoproliferative disorder developed after BMT (n = 27) or organ (n = 31) transplantation received 0.2 mg/kg/d of specific anti-CD21 and anti-CD24 murine monoclonal antibodies (MoAbs) for 10 days. The treatment was well tolerated. Thirty-six of the 59 episodes of BLPD in the 58 patients presented complete remission (61%). The relapse rate was low (3 of 36, 8%). Multivariate analysis identified the following risk factors for partial or no response to anti-B-cell MoAb therapy: multivisceral disease (P </= .005), central nervous system involvement (P </= .05), and late onset of BLPD (P </= .005). The overall long-term survival was 46% (median follow-up, 61 months); it was lower among BMT patients (35%) than organ transplant patients (55%). None of the patients who had received BMT for hematological malignancy survived for 1 year. Eight of these 11 patients presented monoclonal BLPD. Tumor burden was the only other variable that contributed significantly to poor survival. Thus, as assessed from this long-term study, the use of anti-B-cell MoAbs therefore appears to be a safe and relatively effective therapy for severe posttransplant BLPD.
Adolescent↗
[Intensive therapy in non-Hodgkins lymphoma. Indications and modalities].
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Adult↗
Cytotoxic T cell response against the chimeric p210 BCR-ABL protein in patients with chronic myelogenous leukemia.
Human chronic myelogenous leukemia (CML) is characterized by a translocation between chromosomes 9 and 22 that results in a BCR-ABL fusion gene coding for chimeric proteins. The junctional region of the BCR-ABLb3a2 molecule represents a potential leukemia-specific antigen which could be recognized by cytotoxic T lymphocytes (CTL). In fact, we identified a junctional nonapeptide (SSKALQRPV) which binds to HLA-A2.1 molecules. This peptide, as well as those binding to HLA-A3, -A11, and -B8 molecules (previously identified by others), elicits primary CTL responses in vitro from PBLs of both healthy donors and CML patients. Such CTL recognize HLA-matched, BCR-ABL-positive leukemic cells, implying efficient natural processing and presentation of these junctional peptides. Specific CTL were found at high frequency in 5 of 21 CML patients, suggesting that these epitopes are, to some extent, immunogenic in vivo during the course of the disease. These peptides could be useful for the development of specific immunotherapy in CML patients.
Binding, Competitive↗
Total-body irradiation before bone marrow transplantation for acute leukemia in first or second complete remission. Results and prognostic factors in 326 consecutive patients.
AIM: In order to assess the influence of total-body irradiation (TBI) on the outcome and incidence of complication after bone marrow transplantation (BMT), we retrospectively analyzed our patients treated for acute leukemia and conditioned with TBI prior to BMT. PATIENTS AND METHODS: Between 1980 and 1993, 326 patients referred to our department with acute non-lymphoblastic leukemia (ANLL, n = 182) and acute lymphoblastic leukemia (ALL, n = 144) in complete remission underwent TBI either in single dose (190 patients: 10 Gy administered to the midplane, and 8 Gy to the lungs [STBI]) or in 6 fractions (136 patients: 12 Gy on 3 consecutive days, and 9 Gy to the lungs [FTBI]) before BMT. The male-to-female ratio was 204/122 (1.67), and the median age was 30 years (mean: 30 +/- 11, range: 3 to 63). The patients were analyzed according to 3 instantaneous dose rate groups: 118 patients in the LOW group (< or = 0.048 Gy/min), 188 in the MEDIUM group (> 0.048 and < or = 0.09 Gy/min), and 20 in the HIGH group (> 0.09 cGy/min). Conditioning chemotherapy consisted of cyclophosphamide (CY) alone in 250 patients, CY and other drugs in 54, and 22 patients were conditioned using combinations without CY. Following TBI, allogeneic and autologous BMT were realized respectively in 118 and 208 patients. Median follow-up period was 68 months (mean: 67 +/- 29, range: 24 to 130 months). RESULTS: Five-year survival, LFS, RI and TRM rates were 42%, 40%, 47%, and 24%, respectively. Five-year LFS was 36% in the STBI and 45% in the FTBI group (p = 0.17). It was 36% in the LOW group, 42% in the MEDIUM group, and 30% in the HIGH group (p > 0.05). Five-year RI was 50% in STBI, 43% in FTBI, 55% in LOW, 41% in MEDIUM, and 44% in HIGH groups (STBI vs. FTBI, p = 0.48; LOW vs. MEDIUM, p = 0.03; MEDIUM vs. HIGH, p = 0.68). TRM was not influenced significantly by the different TBI techniques. When analyzing separately the influence of fractionation and the instantaneous dose rate either in ANLL or ALL patients, no difference in terms of survival and LFS was observed. Fractionation did not influence the 5-year RI both in ANLL and ALL patients. However, among the patients with ANLL, 5-year RI was significantly higher (58%) in the LOW group than the MEDIUM group (31%, p = 0.001), whereas instantaneous dose rate did not significantly influence the RI in ALL patients. The 5-year TRM rate was significantly higher in allogeneic BMT group both in ANLL (37%) and ALL (37%) patients than those treated by autologous BMT (ANLL: 15%, ALL: 18%; p = 0.002 and 0.02, respectively). The 5-year estimated interstitial pneumonitis (IP) and cataract incidence rates were 22% and 19%, respectively, in all patients. IP incidence seemed to be higher in the HIGH group (46%) than the MEDIUM (19%, p = 0.05) or LOW (25%, p = 0.15) groups. Furthermore, cataract incidence was significantly influenced by fractionation (STBI vs. FTBI, 29% vs. 9%; p = 0.003) and instantaneous dose rate (LOW vs. MEDIUM vs. HIGH, 0% vs. 27% vs. 33%; p < 0.0001). Multivariate analyses revealed that the best factors influencing the survival were 1st CR (p = 0.0007), age < or = 40 years (p = 0.003), and BMT after 1985 (p = 0.008). The RI was influenced independently only by the remission status (p = 0.0002). On the other hand, the TRM rate was lower in patients who did not experience graft-vs.-host disease (GvHD, p < 0.0001), and in those treated after 1985 (p = 0.0005). GvHD was the only independent factor involved in the development of IP (p = 0.01). When considering the cataract incidence, the only independent factor was the instantaneous dose rate (p = 0.0008). CONCLUSION: The outcome of BMT patients conditioned with TBI for acute leukemia was not significantly influenced by the TBI technique, and TRM seemed to be lower in patients treated after 1985. On the other hand, cataract incidence was significantly influenced by the instantaneous dose rate.
Adolescent↗
Autologous hematopoietic stem cell transplantation as salvage treatment for advanced B cell chronic lymphocytic leukemia.
Given the generally poor outcome of advanced B cell chronic lymphocytic leukemia, experimental approaches are warranted, especially for younger patients in whom classical treatments have failed. We therefore conducted a prospective single-center study, using polychemotherapy (ESHAP) to prepare patients for hematopoietic stem cell collection and autologous stem cell transplantation as consolidation therapy. Twenty patients entered the study. An adequate response to ESHAP was obtained in 13 patients, and sufficient stem cells for grafting were obtained in eight of the 12 patients who underwent the collection procedure. Six of these grafted patients are alive in complete clinical remission a median of 30 months after transplantation. It should be noted that we were only able to graft 40% of the patients enrolled in this study, either because a new remission could not be obtained or because not enough hematopoietic stem cells could be collected. This argues for stem cell collection as soon as a first remission is obtained, even if the autograft is done later in the course of the disease.
Adult↗
Prognostic factors for survival and response after high-dose therapy and autologous stem cell transplantation in systemic AL amyloidosis: a report on 21 patients.
We retrospectively investigated the feasibility and the toxicity of autologous stem cell transplantation (ASCT) in 21 cases of systemic amyloidosis (AL). The conditioning regimens consisted of high-dose melphalan (HDM) alone (n = 18) or in combination with 12 Gy total body irradiation (n = 3). Toxic death rate was high: 9/21 patients (43%) died within the first month following ASCT, and 10/12 surviving patients achieved a response. With a median follow-up of 14 months, the OS and the EFS rates at 4 years were 57.1% (+/-10.8) and 29.9% (+/-14.5) respectively for the whole group. The major prognostic factor for both response and survival was the number of clinical manifestations at the time of ASCT, of the following five criteria, i.e. creatinine clearance < 30 ml/min, nephrotic syndrome with urinary protein excretion > 3000 mg/24 h, congestive heart failure, neuropathy, or hepatomegaly associated with alkaline phosphatase level > 200 IU/l. For patients presenting with two or more clinical manifestations the 4-year OS and EFS were both 11.1% compared with 91.7% and 46.3% respectively in patients with fewer than two clinical manifestations at the time of ACST. We conclude that ASCT is feasible in AL in a subset of patients with fewer than two clinical manifestations at the time of ASCT. Given the severe extra-haematological toxicity, ASCT should not be considered in other cases.
Adult↗
CD8hi+CD57+ T lymphocytes are enriched in antigen-specific T cells capable of down-modulating cytotoxic activity.
Major expansions of CD8hi+CD57+ T lymphocytes frequently occur during human immunodeficiency virus (HIV) infection and after transplantation. To investigate mechanisms of such cell expansion, we compared the activation and functional status of CD8hi+CD57+ and CD57-peripheral blood lymphocytes (PBL) from normal, bone marrow transplantation (BMT) and HIV+ donors. The CD8hi+CD57+ PBL from BMT and HIV+ donors preferentially displayed CD38 and HLA-DR activation markers without correlation between CD8hi+CD57+ percentages and HIV load, the CD45RA+ isoform in all ex vivo conditions but acquired CD45RO after in vitro expansion, CD11b and CD11c in BMT and HIV+ donors but decreased expression of CD62-L, VLA-2 and VLA-6. The CD8hi+CD57+ cells were positive for perforin and granzyme B and spontaneously mediated cytolytic activity in a CD3-redirected assay. In contrast the inhibitor of cytolytic functions (ICF) produced by CD8hi+CD57+ cells down-modulated the CD3-redirected cytolytic activity but only at low levels of CD3 cross-linking. While CD3-triggering induced a low, if any, short-term proliferation of CD8+CD57+ cells, this subset could be amplified after long-term stimulation either with mitogens or with HIV antigens, thereby enriched in HIV-specific T cells producing tumor necrosis factor-alpha. Altogether these data suggest that CD8hi+CD57+ cells represent a terminal differentiation state of activated effector cytotoxic T lymphocytes which are enriched in antigen-specific T cells and down-modulate their own cytolytic potential, thus participating in a negative control of effector cell functions during persistent viral infections or transplantations.
CD57 Antigens↗
Sequential chlorambucil and prednisone as second line therapy in gastric malt lymphoma resistant to Helicobacter pylori eradication. A case report in an octogenarian patient.
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Aged↗
Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?
PURPOSE: Organ recipients are at a high risk of posttransplant lymphoproliferative disorders (PTLD) as a result of immunosuppressive therapy. Most B-cell lymphomas are associated with Epstein-Barr virus (EBV) infection. We describe a morphologically and clinically distinct group of PTLD in 11 patients that occurred late after organ transplantation and were not associated with EBV. PATIENTS AND METHODS: There were seven kidney, three heart, and one liver transplant recipients (group I). The clinical manifestations, pathologic findings, treatment, and outcome were compared with those in 21 patients with EBV-associated PTLD treated in our institution (group II). EBV was detected with at least two techniques: Epstein-Barr-encoded RNA (EBER) in situ hybridization with EBER 1 + 2 probes, Southern blotting, and detection of latent membrane protein 1 (LMP1) expression by immunohistochemistry. RESULTS: The time between transplantation and the diagnosis of lymphoma ranged from 180 to 10,220 days in group I (mean, 2,234; median, 1,800) and from 60 to 2,100 days in group II (mean, 546; median, 180), and was significantly shorter in group II (P = .02). Among 19 tumors diagnosed within 2 years after the graft, 16 were associated with EBV; among 13 tumors diagnosed after more than 2 years, only five were associated with EBV. All of the B-cell PTLDs in group I were classified as monomorphic, meeting the criteria of B diffuse large-cell lymphoma (B-DLCL) with a component of immunoblasts, and genotyping confirmed their monoclonality. Three tumors were T-cell pleomorphic lymphomas. Tumor sites were mainly bone marrow and lymph nodes. Overall median survival was 1 month in group I and 37 months in group II, with two patients still alive in group I and nine in group II. The survival time was significantly longer in group II (P < .01). CONCLUSION: EBV-negative PTLD may be a late serious complication of organ transplantation. Half the tumors observed after kidney transplantation in our center were not associated with EBV and emerged after more than 5 years, which suggests the number of EBV-negative PTLDs in organ recipients might increase with time.
Adolescent↗
Activity of fludarabine in previously treated Waldenström's macroglobulinemia: a report of 71 cases. Groupe Coopératif Macroglobulinémie.
PURPOSE: There is no consensus on the treatment of patients with Waldenström's macroglobulinemia (WM) who develop primary or secondary resistance to frontline therapies. We report our experience on the activity and toxicity of fludarabine in 71 patients with WM resistant to prior chemotherapy regimens. PATIENTS AND METHODS: From January 1991 to June 1995, 71 patients were included in this retrospective study. The median age, median time from diagnosis to treatment, median immunoglobulin M (IgM) level, and median number of previous treatments were 68 years (range, 42 to 81), 5.9 years (range, 0.6 to 20), 35 g/L (range, 5 to 126), and two (range, one to four), respectively. RESULTS: Seventy-one patients received a median of six courses of fludarabine. Twenty-one (30%) responded with a partial response and 50 (70%) were considered as treatment failures. Forty-six patients died: 10 in the responder group and 36 in the failure group. Twenty-five patients were alive with a median follow-up time of 34 months. The overall median survival time of all treated patients was 23 months. The time to treatment failure was 32 months. The only factor that favorably influenced the response to fludarabine was a longer interval between the first treatment and the start of fludarabine. Pretreatment factors associated with shorter survival in the entire population were hemoglobin level less than 95 g/L (P = .02) and platelet count less than 75 x 10(9)/L (P = .02). CONCLUSION: The responses rate in this population with a poor prognosis is close to that reported in shorter series. Patients with WM who are resistant to alkylating agents should be identified early, so that salvage therapy with nucleoside analogs can be started without delay.
Adult↗
Severe autoimmune hemolytic anemia in eight patients treated with fludarabine.
We have used fludarabine to treat 36 patients with various lymphoid malignancies, including 29 with chronic lymphocytic leukemia (CLL). All these patients were heavily pretreated, and FAMP was prescribed on a compassionate basis. Eight patients (22%) developed severe autoimmune hemolytic anemia (AIHA) during or after treatment, and one died. Five patients had no previous history of hemolysis. These cases confirm the high incidence of AIHA after FAMP and suggest that the use of highly effective lymphocytotoxic agents such as fludarabine in heavily pretreated patients increases the risk of AIHA in CLL and other lymphoproliferative disorders.
Aged↗
[Neutrophilic eccrine hidradenitis associated with relapse of acute myeloblastic leukemia].
BACKGROUND: Neutrophilic eccrine hidradentitis is a recently described clinical entity. Most reported cases have occurred in patients given chemotherapy for acute myelogenous leukemia, suggesting a drug induced mechanism. Some authors have considered however that neutrophilic eccrine hidradenitis belongs to the group of neutrophilic dermatoses. CASE REPORT: We observed neutrophilic eccrine hidradentitis in a 48-year-old man which developed when he suffered a relapse of acute leukemia. He had not been given chemotherapy in the preceding months. DISCUSSION: This case favors the hypothesis that neutrophilic eccrine hidradenitis is associated with myeloid hemotology disorders and not a complications secondary to treatment.
Hidradenitis↗
Expansion of CD4+CD7- T cells, a memory subset with preferential interleukin-4 production, after bone marrow transplantation.
BACKGROUND: Inadequate reconstitution of CD4+ lymphocyte and interleukin (IL)-2 production defect are observed after bone marrow or peripheral blood stem cell transplantation (SCT). METHODS: We studied immune reconstitution after SCT in 33 consecutive patients who received allogeneic SCT (17 patients) or autologous SCT (16 patients). The aims were to assess the regeneration of the CD4+ T-cell subset with regard to helper cell differentiation. CD4+ T-cell subset regeneration and expansion of the CD4+CD7- subset were studied by immunofluorescence analysis. CD4+CD7- cell cytokine secretion was analyzed after cell sorting and costimulation of the CD3 and CD28 pathways, in enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction assays. RESULTS: We report a relative expansion of the CD4+CD7- subset within CD4+ T cells, detected as early as 1 month after bone marrow transplantation and decreasing after day 60. CD4+CD7- T cells preferentially expressed CD45RO and activation markers such as CD57, CD25, and HLA-DR. No relationship was observed between the CD4+CD7- expansion and transplant-related complications. We observed no significant IL-2 production in supernatants from sorted CD4+CD7- T cells, whereas IL-4 levels were comparable to those produced by cells from normal individuals. Autologous CD4+CD7+ cells showed little, if any, IL-4 production, and IL-2 production was lower than that by normal CD4+CD7+ T cells. Reverse transcription-polymerase chain reaction assays showed similar amounts of interferon-gamma transcripts in the two subsets; tumor necrosis factor-alpha, IL-4, and IL-10 transcripts were detected in CD4+CD7- T cells but not in their CD4+CD7+ counterparts. CONCLUSIONS: These data confirm the IL-2 production defect after bone marrow transplantation and suggest that the CD4+CD7- T-cell subset might be preferentially involved in the enhanced production of IL-4 and low production of IL-2. These data show that the early immune reconstitution in CD4+ T cells after SCT preferentially involves memory T cells with a Th0/Th2 differentiation that might participate in the T-helper cell defect.
Adult↗