Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between 1990 and 1997, we performed 29 allogeneic BMTs for acute lymphoblastic leukemia (ALL) patients with HLA-identical sibs. Their median age was 31 years (range 15 to 43); there were 15 males and 14 females. The conditioning protocol was Cy-TBI (n = 15), VP16-Cy-TBI(n = 12), CBV (n = 1) and Bu-Cy (n = 1). Cyclosporin and methotrexate were used for GVHD prophylaxis. The median disease-free survival (DFS) was 12 months (range 1 to 92) with an actuarial 4-years DFS of 42.3 per cent. Three patients died of transplant-related complications before 100 days. Relapse occurred in 11 cases at a median time of 5 months (range 3 to 14). All nine patients relapsing within one year died form resistant leukemia. Three patients died of late treatment-related complications. There were 13 survivors (median follow-up 38 months, range 12-98), with 12 in remission. Only four had limited cGVHD, and all had 100 per cent performance scores. One patient also cleared her chronic hepatitis B carrier status due to acquired immunity. The DFS rates amongst CR1 cases and R1/CR2 cases were comparable (p = 0.39). No long-term DFS is obtained from patients with resistant disease (n = 4). The survival results for BMT at CR1 were superior to those using intensive chemotherapy consolidation (p = 0.29), mainly due to poor late results in the chemotherapy arm. For young ALL patients with HLA-matched siblings, the option of BMT should be considered in light of local consolidation survival results.
 ...
PMID:Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia: a single-centre experience. 1041 36

We evaluated the outcome of allogeneic bone marrow transplantation (BMT) for advanced acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) in 383 adult patients in nine Australian adult BMT centres between 1981 and 1997. The median overall survival for the group was 4.8 months, with an estimated 5-year survival of 18%. 28% of patients died of transplant-related toxicities within the first 100 d. Progressive disease was responsible for 48% of deaths. Multi-factor analysis demonstrated that AML (v ALL), disease status (second complete remission [CR2] v others), age (< 40 years) and duration of prior first complete remission (CR1) (> 6 months) were pre-transplant variables significantly associated with improved survival. Acute graft-versus-host disease (GVHD) of any grade reduced the rate of relapse in both AML and ALL, but only grades I-II were associated with improved survival. Both limited and extensive chronic GVHD were associated with increased survival. Only patients with AML in untreated first relapse or CR2, with a duration of CR1 > 6 months, or patients with T ALL, had a 5-year survival > 20%. Transplants for AML in induction failure or pre-B ALL in untreated first relapse or CR2 had an intermediate outcome, with 5-year survival of 10-20%. A 5-year survival of < 10% was observed for patients transplanted for ALL in induction failure or for pre-B ALL or AML in refractory first relapse or beyond CR2. These results suggest that for most adult patients with advanced acute leukaemia an allograft offers only a small chance of cure.
 ...
PMID:Factors affecting the outcome of allogeneic bone marrow transplantation for adult patients with refractory or relapsed acute leukaemia. 1058 35

Several prospective randomized trials in acute myelocytic leukemia (AML) documented a lower relapse rate with autologous bone marrow transplantation (ABMT) than with conventional chemotherapy. However, they also identified some transplant difficulties, such as failure to collect sufficient numbers of stem cells, slow kinetics of engraftment, and a high transplant-related mortality that diminished or negated positive impact on overall survival. Data for ABMT are inconclusive in acute lymphocytic leukemia (ALL) in adults. We retrospectively analyzed patients with acute leukemia autografted with marrow purged with mafosfamide after January 1983 in our institution. The population comprised 229 consecutive patients; 165 with AML [123 in first remission (CR1), 32 in second remission (CR2)]; 61 with ALL (46 in CR1, 4 in CR2); and 3 with undifferentiated acute leukemia. All patients were autografted with marrow purged with mafosfamide. Mafosfamide was given at a constant dose of 50 microg/mL in 103 and adjusted individually to produce a CFU-GM LD 95 (5% residual CFU-GM post purging) in 126. The outcome was analyzed for correlation with patient characteristics, the disease including cytogenetics, and the graft itself. Prognostic factors identified by multivariate analysis were used to derive a prognostic classification. Patients receiving higher doses of marrow submitted to purging (>5.46 x 10(4) CFU-GM/kg) experienced a lower treatment-related mortality (RR = 0.11, p = 0.005) and a higher leukemia-free (RR = 0.5, p = 0.005) and overall survival (RR = 0.4, p = 0.001). Patients receiving <0.004% CFU-GM of marrow actually infused post purging had a lower relapse rate (RR = 0.51, p = 0.003). Modeling of prognostic groups identified good-, intermediate-, and poor-risk categories. Patients receiving a stem cell dose evaluated before purging of >5.46 x 10(4) CFU-GM/kg and doses actually infused post purging of < or =0.02 x 10(4)/kg had a treatment-related mortality of only 2+/-2%, a leukemia-free survival of 70%, and an overall survival of 77+/-7% at 10 years. In this study of autotransplantation for acute leukemia using mafosfamide-purged marrow, the stem cell dose used for purging and the intensity of purging were the most important factors predicting outcome.
 ...
PMID:Importance of marrow dose on posttransplant outcome in acute leukemia: models derived from patients autografted with mafosfamide-purged marrow at a single institution. 1064

The purpose of this study was to assess the safety and efficacy of stem cell transplantation (SCT) mainly autologous SCT as consolidation therapy in APL patients who relapsed and achieved a second complete remission (CR2). Fifty adult patients with a first relapsed APL, of whom 39 had been previously treated with ATRA, entered a multicenter trial of oral ATRA until complete remission (CR) achievement followed by timed sequential chemotherapy (EMA combining etoposide 200 mg/m2/day for 3 days, mitoxantrone 12 mg/m2/day for 3 days, and cytarabine 500 mg/m2/day for two sequences of 3 days). EMA was started either after CR achievement, or on day 1 of ATRA because of initial white blood cell (WBC) counts >5 x 10(9)/l, or rapidly added to ATRA in order to prevent ATRA syndrome because WBC count increased under ATRA. Forty-five patients (90%, 95% CI 78%-97%) were in CR after induction therapy. Five patients died from infection during aplasia following EMA chemotherapy. Eleven patients who achieved CR had a familial HLA-identical donor and were allografted. The median disease-free survival (DFS) of allografted patients was 8.2 months. The 34 other CR patients were scheduled for autologous peripheral blood (PB) SCT (intent-to-treat group). Actually, autologous transplantation was only carried out in 22 patients (65%) (17 PBSCT and five autologous bone marrow transplantation (BMT)). Reasons for not autografting were early relapse (three patients), severe toxicity of EMA chemotherapy (six patients), and refusal or failure of stem cell harvest (three patients). The 3-year DFS rate of patients actually autografted was 77%. Among the 17 autografted patients still in CR2, nine patients have already reached a longer CR2 than first CR (CR1). Results of detection of PML/RARalpha by RT-PCR after autologous transplantation show negative findings in eight of the nine patients tested. We conclude that (1) ATRA combined to EMA chemotherapy is effective in the treatment of relapsed APL; (2) allogeneic BMT may be too toxic after salvage treatment including EMA intensive chemotherapy; (3) clinical outcome of autografted patients and preliminary molecular results regarding detection of PML/RARalpha after autologous PBSCT are encouraging.
Leukemia 2000 Jun
PMID:Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation. APL Study Group. Acute promyelocytic leukemia. 1086 65

Myeloablation and immunosuppression were considered to be the two major roles of the conditioning regimens for allogeneic stem cell transplantation to facilitate engraftment. It has turned out, however, that immunosuppression is more important and myeloablation is not necessary for engraftment. At the same time, it is considered that the major anti-tumor effect of allogeneic stem cell transplantation depends on the graft-versus-leukemia effect, not on the conditioning regimen itself. In patients with CML who relapsed after allogeneic transplantation, for example, infusion of donor lymphocytes can induce a second complete remission. Non-myeloablative stem cell transplantation (NST) was developed in the late 90s based on these theories. Low-dose, less toxic, so-called "non-myeloablative" preparative regimens have been designed not to eradicate the malignancies, but to provide sufficient immunosuppression to allow donor cells to engraft, while the graft-versus-malignancy effects eradicate the tumor. This strategy permits allogeneic transplantation to be used in patients who are not eligible for conventional, often myeloablative, transplantation because of advanced age or organ dysfunction. Non-myeloablative preparative regimens contain purine analogs, such as fludarabine or cladribine. The NST regimen being used at the National Cancer Center Hospital, Tokyo, Japan, consists of cladribine (0.11 mg/kg x 6 days), busulfan (4 mg/kg x 2 days) and rabbit anti-thymocyte globulin (2.5 mg/kg x 4 days). We enrolled 6 patients in this NST protocol so far: 1 with severe aplastic anemia (sibling-PBSCT), 2 with MDS-RA (1 for sibling-PBSCT and 1 for matched uBMT), 1 with AML-CR2 (matched uBMT), 1 with AML-CR3 (sibling-PBSCT), and 1 with relapsed AML (mismatched related PBSCT). All patients achieved engraftment within 14 days with complete donor chimerism. In addition to leukemias, a graft-versus-malignancy effect was also reported in allogeneic NST of solid tumors, such as renal cell carcinoma and malignant melanoma. The long-term efficacy of NST remains to be determined, and further clinical trials are warranted.
 ...
PMID:[Non-myeloablative stem cell transplant]. 1089 4

Despite improvements in HLA typing, graft-versus-host disease (GVHD) continues to impair the results after volunteer unrelated donor bone marrow transplantation (VUD-BMT) in adult patients compared with matched sibling BMT. Here, the outcome after VUD-BMT using a specific regimen with high-dose anti-T-lymphocyte globulin (ATG) was analysed. Fifty-five adult patients, median age 34 years (range 17-55 years), with acute or chronic leukaemia or myelodysplastic syndrome (MDS) were transplanted in first complete remission (CR1)/first chronic phase (CP1) (early disease) (n = 21) or in advanced (CR2/CP2, no remission) disease (n = 34) from an unrelated marrow donor. GVHD prophylaxis consisted of ATG-S (Fresenius) 60-90 mg/kg b.w. prior to transplantation, in addition to cyclosporin A and short-course methotrexate. Graft failure did not occur and white blood cell count (WBC) > 1.0 x 10(9)/l was reached at median day +16. The cumulative incidence of acute (a)GVHD grade II-IV was 15% [95% CI (8%, 28%)] and of chronic GVHD was 51% [95% CI (38%, 68%)]. The cumulative incidence of relapse within 1 year was 0% [95% CI (0%, 19%)] and 21% [95% CI (11%, 40%)] for patients with early and advanced disease respectively. With a median follow-up of 28 months (range 16-45 months), 2-year disease-free and overall survival for patients transplanted in CR1/CP1 was 81% and 81% [95% CI (64%, 98%)], respectively, and for patients with advanced disease was 33% [95% CI (17%, 50%)] and 40% [95% CI (23%, 57%)] respectively. Complete and persistent donor chimaerism was seen in 77.5% of 40 patients evaluated. All 14 chronic myeloid leukaemia (CML)-CP1 patients became bcr-abl negative within 250 d. High-dose ATG pretransplant results in a low incidence of severe aGVHD without compromising donor chimaerism or elimination of minimal residual disease. Our results are similar to data obtained after matched sibling donor transplantation.
 ...
PMID:Allogeneic bone marrow transplantation from unrelated donors using in vivo anti-T-cell globulin. 1109 Dec 17

Autologous transplantation is a treatment option for relapsed childhood acute lymphoblastic leukemia (ALL) in second complete remission (CR2) when a suitable donor is not available. In an attempt to prevent relapses originating from graft leukemic contamination, the experimental protocol of in vitro purification of leukapheretic products with monoclonal antibodies (MoAbs), previously reported for adults, was adopted in 11 of 12 consecutive patients (median age, 9 years) with B cell precursor ALL in CR2 after late relapse (median, 37; range, 31-51 months after the onset) enrolled between July 1997 and July 1999 at a single pediatric center. At a median of 12 days after the mobilizing chemotherapy followed by G-CSF, a median of 13.9 (range, 5.9-18.7) x 10(6) CD34+ cells/kg were collected from each patient and a median of 7.5 (range, 4.1-12.6) x 10(6) CD34+ cells/kg underwent the purification procedure. The first step of immunorosetting allowed a one-log reduction of the total cell count, by eliminating more than 90% of the CD11b+ cells; the second step, performed after incubation with anti-CD19 MoAbs, allowed the depletion of 99% (range, 93-100) of the CD19+ cells, kept within the magnetic field of the immunodepletion column, with a median recovery of 73% (range, 55-87) of the collected CD34+ cells. Molecular analysis assessed the in vitro eradication of detectable leukemic cells. A median reinfusion of 5.2 (range, 3.2-9.1) x 10(6) CD34+ cells/kg for each patient (median viability, 90%), after conditioning with the 'TBI-VP16-CY' regimen, allowed prompt engraftment and immunological reconstitution; no patients experienced severe transplant-related toxicity or major infections. One patient relapsed 7 months after transplantation, while 10 patients are alive in clinical and molecular remission, at a median follow-up of 29 months (range, 15-40) (2-year EFS, 89%, s.e. 9). In conclusion, the procedure proved to be reproducible for pediatric purified autografting, highly efficient concerning stem cell recovery and depletion of leukemia-lineage specific cells, and promising in terms of final outcome.
Leukemia 2001 Jan
PMID:Purified autologous grafting in childhood acute lymphoblastic leukemia in second remission: evidence for long-term clinical and molecular remissions. 1124 99

Leukaemic patients with advanced disease and severe fungal infections as well as older patients with substantial co-morbidity are usually excluded from conventional allotransplantation because of increased morbidity and mortality. We approached allogeneic transplantation in four patients with a median age of 62 years (one chronic myeloid leukaemia in blast crisis, one high-risk acute myeloid leukaemia (AML) in first complete remission (CR1), one AML in 2nd relapse, one AML in CR2 with pre-existing fungal lung infections (two aspergillus, two mucor) and additional co-morbidity (diabetes n = 2, aortic aneurysm n = 1, arterial sclerosis n = 2) by combining non-myeloablative conditioning with an intensified supportive care regimen, including amphotericin B and 4-12 (median 9) prophylactic granulocyte transfusions from granulocyte colony-stimulating factor (G-CSF)-stimulated volunteer donors. G-CSF was also given to patients until neutrophil recovery. All four patients recovered to a neutrophil count of 0.5 x 109/l after a median of 11.5 d (range 11-13 d). Prophylactic granulocyte transfusions also reduced the need for platelet transfusions and minimized mucositis. All patients were discharged at a median of 25 d (range 18-59 d) and are alive and well after a median follow-up of > 390 d (range 336-417 d) without evidence of leukaemia. Regression of the fungal lesions was documented in three patients, with a slight progression detected by computerized tomography scan of the chest in one patient. We conclude that pulmonary fungal infections are not a contraindication for allogeneic stem cell transplantation, if non-myeloablative conditioning regimens are used in combination with granulocyte transfusions, intravenous amphotericin B and G-CSF.
 ...
PMID:Older patients with high-risk fungal infections can be successfully allografted using non-myeloablative conditioning in combination with intensified supportive care regimens. 1138 Apr 15

Acute promyelocytic leukemia (APL) is characterized by a specific gene rearrangement and the generation of the PML-RARalpha fusion transcript which results from a translocation between chromosomes 15 and 17. Targeted therapy with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy results in an apparent cure in 70-80% of patients. Both allogeneic (ALLO) and autologous (AUTO) hematopoietic stem cell transplantation (HSCT) are effective in acute myeloid leukemia (AML), but their role in APL is not clear given the excellent outcome with ATRA and chemotherapy. Several retrospective studies have analyzed the outcome of patients undergoing AUTO or ALLO-HSCT in first (CR1) or second (CR2) complete remission. Most of these studies have shown significant transplant-related mortality (TRM) with ALLO-HSCT, but a reduction in relapse rate compared with AUTO-HSCT. The high TRM with ALLO-HSCT and the excellent outcome with ATRA and chemotherapy do not justify recommending this procedure for the majority of patients in CR1. The role of AUTO-HSCT in CR1 also is unclear. A small subset of patients at high risk of relapse, possibly identifiable by a high white blood cell count at presentation may benefit from HSCT. Most patients with relapsed disease achieve CR2 with ATRA, arsenic trioxide, or combination therapy. However, it is not known if these responses are sustained or if consolidation with HSCT has a place in this setting. The outcome of AUTO-HSCT in CR2 using stem cells that are negative for PML-RARalpha is excellent. It is unclear whether ALLO-HSCT from an HLA-identical sibling is superior to AUTO-HSCT with PML-RARalpha-negative cells in CR2 since the former would be associated with graft-versus-leukemia effects and the latter with lower TRM. Alternatively, arsenic trioxide or re-treatment with ATRA, followed by intensive chemotherapy may also be effective. A randomized prospective clinical trial, or a retrospective analysis of the available data would be useful in answering this critical question.
 ...
PMID:The role of bone marrow transplantation in acute promyelocytic leukemia. 1153 88

The blastic variant (BV) form of mantle cell lymphoma (MCL) is considered to be a very aggressive subtype of non-Hodgkin's lymphoma (NHL). In order to determine its clinico-biological features and response to therapy we studied 33 patients (17%) out of 187 suffering from MCL who were diagnosed with a BV of MCL. Blastic variant was diagnosed according to histopathological patterns, immunophenotyping, and bcl1 gene rearrangement and/or cyclin D1 overexpression. Three patients initially diagnosed with large cell NHL were classified as BV. Patients received front-line therapy including CHOP-like regimen or CVP (n = 29), or chlorambucil (n = 4) and CHOP or ESAP as second-line therapy. High-dose intensification with stem cell transplantation (SCT) was performed in 11 cases (autoSCT, n = 8; alloSCT, n = 3). All but two patients were in complete remission (CR) at the time of transplant (CR1, n = 5; CR2, n = 4). Clinical and biological characteristics did not differ from those of the common form of MCL. The median age was 62 years (29-80), with a sex ratio (M/F) of 2.6:1. Of the 33 patients, 66% had extranodal site involvement, 85% had an Ann Arbor stage IV, and 82% had peripheral lymphadenopathy. Circulating lymphomatous cells were seen in 48% of cases. Twelve patients (36%) entered a CR1 with a median duration of 11 months. Fifteen patients (46%) failed to respond and rapidly died of progressive disease. Second-line therapy led to a 26% (6/23) CR2 rate. Nine patients relapsed after high-dose therapy. Twenty-two of the 33 patients (66%) died of refractory or progressive disease. Median overall survival (OS) time was 14.5 months for the 33 BV patients as compared to 53 months for the 154 patients with a common form of MCL, P <0.0001. In the univariate analysis, OS was influenced by age, extranodal site involvement, circulating lymphomatous cells, and international prognosis index (IPI). In the multivariate analysis, only IPI affected OS: patients with IPI > or =2 had 8 months median OS as compared to 36 months median OS for patients with IPI <2, P = 0.003. Blastic variant is one of the worst forms of NHL. An improved recognition of BV of MCL is required, particularly in high-grade CD5+ NHL using immunophenotyping and bcl1 molecular study. Standard therapy using anthracycline or even high-dose intensification produce poor results and an alternative treatment should be proposed to such patients.
Leukemia 2001 Nov
PMID:Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype. 1220 Jul 19


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>