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

We performed retrospective analysis of hepatic veno-occlusive disease (VOD) in 57 cases with leukemia after allogeneic bone marrow transplantation (BMT). Prostaglandin E1 (PGE1) was used to prevent VOD in 8 cases at a dose of 0.3 micrograms/kg/hr from day -8 to day 30. No VOD was noted in the PGE1 group, while the incidence of VOD was 8/49 (16.3%) in the non PGE1 group. In twelve patients with pretransplant liver dysfunction, VOD was noted in 0/3 in the PGE1 group and 4/9 (44.4%) in the non PGE1 group, respectively. However, prophylactic effects of PGE1 on VOD is not significant in this study, so further studies are needed to determine the efficacy of PGE1. One of 8 patients with PGE1 prophylaxis had edema and erythema on extremities, however, severe toxicity was not experienced.
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PMID:[A trial use of prostaglandin E1 for prevention of hepatic veno-occlusive disease after allogeneic bone marrow transplantation]. 796 53

In a retrospective multicentre study, we analyzed 184 consecutive patients who underwent bone marrow transplantation (BMT) from identical siblings for adult acute lymphoblastic leukemia in first complete remission between March 1980 and May 1989. The main causes of transplant-related mortality were GVHD and interstitial pneumonitis. Univariate and multivariate analyses identified the mode of total body irradiation (TBI) as the only independent predictive factor of transplant-related mortality. Ninety-one patients received single-dose TBI and 93 received fractionated-dose TBI as part of the conditioning regimen prior to BMT. Transplant-related mortality was more frequent in the single dose group (p = 0.017). The incidence of interstitial pneumonitis, acute and chronic GVHD and veno-occlusive disease of the liver was not statistically different between the two irradiation groups. However, fatal interstitial pneumonitis was significantly more frequent in the single dose irradiation group (p = 0.031). These results show that transplant-related mortality is closely associated with the mode of TBI administration. The increased relapse rate in the fractionated group explains why there was no difference between the two groups in terms of overall leukemia-free survival.
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PMID:Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia in first complete remission: factors predictive of transplant-related mortality and influence of total body irradiation modalities. 813 42

Case 1: A 26-year-old female was admitted because of leukocytosis with 43.6% myeloblasts and 33.6% monocytes, and trilineage myelodysplasia (T-MDS) was detected on bone marrow (BM) smear. She was diagnosed as having acute myeloid leukemia (AML) (M4) with T-MDS and was treated with the Japan Adult Leukemia Study Group (JALSG) AML87 protocol. After completion of chemotherapy, leukemic myeloblasts remained minimally and myelodysplastic changes were still detected on BM smear. She underwent allo-BMT from an HLA-identical sibling. The conditioning regimen consisted of busulfan and cyclophosphamide. Cyclosporine A and short term methotrexate were administered prophylactically for graft-versus-host disease (GVHD). She developed slight veno-occlusive disease and pancytopenia, which improved soon. She is surviving free of disease for 37 months from BMT. Case 2: A 41-year-old male was diagnosed as having T-MDS AML (M2) and achieved complete remission with the AML89 protocol, but relapsed soon. He underwent allo-BMT from an HLA-identical sibling. The conditioning regimen and prophylaxis against GVHD were the same as in case 1. He developed mild acute GVHD, pleural effusion and later mild chronic GVHD. These improved soon. He is surviving free of disease for 21 months from BMT. Some reports suggest that intensive chemotherapy can induce CR in 40%-70% of patients with T-MDS AML, but most of them tend to relapse and rarely survive long. We consider that the best strategy for treatment of T-MDS AML is allo-BMT at present, if suitable donors are available.
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PMID:[Allogeneic bone marrow transplantation for two patients with acute myeloid leukemia with trilineage myelodysplasia (T-MDS)]. 813 16

Between October 1988 and December 1992, 167 patients with leukemia receiving marrow transplants from HLA-identical donors and conditioned with cyclophosphamide (120 mg/kg) were randomized to additional treatment with either busulfan (16 mg/kg, n = 88) or total body irradiation (TBI; n = 79). The busulfan-treated patients had an increased cumulative incidence of veno-occlusive disease of the liver, ie, 12% compared with 1% in the TBI group (P = .009). Furthermore, hemorrhagic cystitis occurred in 24% of the busulfan patients versus 8% in the TBI patients (P = .003). In patients with advanced disease beyond first remission or first chronic phase, transplantation-related mortality was 62% among the busulfan-treated patients compared with 12% among the TBI recipients (P = .002). These differences between the two groups were statistically significant in multivariate analysis. Seizures were seen in 6% of the busulfan-treated patients and were absent in the TBI group (P = .03). Grade II-IV of acute graft-versus-host disease (GVHD) was similar in the two groups, but grade III-IV and chronic disease was more common in the busulfan-treated group (P = .04). Death associated with GVHD occurred in 17% of the busulfan-treated group and 2% of the TBI group (P = .003). Patients treated with busulfan had a 3-year actuarial survival of 62%, which was worse than the 76% among those treated with TBI (P < .03). In multivariate analysis, poor survival was associated with advanced disease (P < .0001), no posttransplant septicemia (P = .0006), grade II-IV GVHD (P = .006), and busulfan treatment (P < .02). The incidence of relapse did not differ between the two groups. Relapse-free survival was also similar in the two treatment groups on analysis of data from all patients, children, patients with early disease, and those with acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. However, in adults (P = .05) and patients with advanced disease (P = .005), leukemia-free survival was significantly better in those treated with TBI. We conclude that patients treated with busulfan have more early toxicity and an increased transplant-related mortality in patients with advanced disease. TBI is therefore the treatment of choice, especially in adults and patients with advanced disease. However, busulfan is an acceptable alternative for patients with early disease and for those in whom TBI is not feasible.
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PMID:A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. 816 51

Between 1980 and 1988, 126 patients with leukemia were treated with piperazinedione and fractionated total body irradiation (TBI) followed by allogeneic bone marrow transplantation from HLA matched siblings. Sixty-one patients had acute myelogenous leukemia, 46 acute lymphoblastic leukemia, and 19 chronic myelogenous leukemia. Patients with acute leukemia in first complete remission were transplanted only if perceived to have a low probability of remaining in remission with conventional therapy. The toxicity from the preparative regimen was similar to that of cyclophosphamide and TBI except that none of the patients in the study had hemorrhagic cystitis or veno-occlusive disease. After a median follow up of 114 months, 29 patients (23%) are still alive without relapse. The survival of patients with acute myelogenous or lymphoblastic leukemia transplanted in their first remission were 35% and 43%, respectively. The survival of patients transplanted in their first chronic phase of chronic myelogenous leukemia was 60%. The results of this preparative regimen are comparable to those of cyclophosphamide and TBI.
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PMID:Allogeneic bone marrow transplantation for leukemia following piperazinedione and fractionated total body irradiation. 817

Since June 1985, 121 patients with follicular lymphoma aged 24-61 years (median 43) have received myeloablative therapy (cyclophosphamide: 60 mg/kg x 2, + total body irradiation: 200 cGy x 6) with autologous bone marrow transplantation (CY+TBI+ABMT) as consolidation of 2nd or subsequent remission. The marrow mononuclear cell fraction was treated in vitro with anti-CD20 alone and baby rabbit complement at St. Bartholomew's Hospital (SBH) and with the addition of anti-B5 and anti-CD10 at the Dana Farber Cancer Institute (DFCI) prior to reinfusion. There were 4 treatment related deaths, (nonengraftment 1, haemorrhage 1, systemic fungal infection 1, veno-occlusive disease 1). The median time for neutrophil recovery (> 0.5 x 10(9)/1) was 26 days (range 10 to 59 days), and for platelets (> 20 x 10(9)/1), 30 days (range 12 to 73 days). One patient did not engraft and 7 have had delayed recovery of red cells and platelets (> 3 months). Two other patients have subsequently developed acute myelogenous leukaemia and 5, evidence of myelodyplasia. Seventy-one patients continue in unmaintained remission between 3 months and 7 years, with a median follow up of 2.5 years. Forty-three have developed recurrent lymphoma; 98 remain alive. Freedom from progression was the same, irrespective of whether patients received CY + TBI + ABMT whilst in a complete or partial remission and did not depend on the specific remission in which treatment was given (2nd: 90 patients vs. > 2nd: 31 patients).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for follicular lymphoma. 820 13

Refractoriness to platelet transfusions remains a significant problem for oncology patients, occurring in 30% to 70% of multiply transfused recipients with bone marrow failure. Nonimmune causes are often present and include disseminated intravascular coagulation, concurrent use of amphotericin B, infection, presence of palpable spleen, use of antibacterial antibiotics, bleeding, veno-occlusive disease, and fever. Immune causes are also commonly responsible for refractoriness, with HLA alloimmunization dominating the list of immune factors. HLA antibodies can be identified in 25% to 30% of transfused leukemia patients and can be present in as many as 80% of aplastic anemia patients. Developing a consistent approach to managing these refractory patients is essential to preventing and treating bleeding manifestations. An HLA type should be obtained for all patients anticipated to have chronic transfusion requirements. Screening for lymphocytotoxic antibodies can confirm suspected HLA alloimmunization. Histocompatible platelets (cross-match compatible and HLA matched) should be provided for all patients with HLA antibodies. A number of other therapeutic modalities have been used in an effort to manage the alloimmunized patient; most of these methods have had little or no proven benefit. When bleeding develops in the alloimmunized patient, there are few therapeutic choices. If histocompatible platelets are unavailable or unsuccessful, massive platelet transfusions of pooled platelet concentrates are commonly used, although this practice is of no proven benefit. While antifibrinolytic agents have been available for over 30 years, they are only recently being applied to control bleeding in chronic thrombocytopenia. We have successfully managed bleeding episodes in thrombocytopenic bone marrow transplant recipients with the use of epsilon aminocaproic acid. A number of these patients were platelet refractory with demonstrable platelet antibodies. Platelet refractoriness continues to plague multiply transfused oncology patients. While preventative measures may ultimately benefit some patients, this problem will continue to manifest itself. A consistent approach to transfusion support needs to be implemented to best manage this challenging patient population.
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PMID:The platelet-refractory bone marrow transplant patient: prophylaxis and treatment of bleeding. 821 Dec 11

We report the development of a double-cycle elutriation (DCE) technique separating 3 or greater logs of T cells from a stem-cell-enriched marrow fraction and the results of phase I T-cell depletion studies with HLA-disparate related bone marrow transplantation (BMT) donors in two patient groups. In group 1, 10 patients with refractory hematopoietic malignancies received combination chemotherapy, total body irradiation (TBI), and immunosuppression (pre- and post-BMT), and hematopoietic rescue with a marrow transplant, depleted of T cells by elutriation. Potentially to promote engraftment and a graft-versus-leukemia (GVL) effect, 0.5 to 0.75 x 10(5) T cells/kg were added back. All 10 patients engrafted. Five patients developed acute graft-versus-host disease (GVHD; four grade II, one grade III) and two subsequently developed chronic GVHD. Two patients have relapsed (median follow-up, 206 days; range, 46 to 1,035). Four patients died of BMT-related complications (three of infection, one of veno-occlusive disease [VOD]). Four patient are disease-free survivors (median follow-up, 960 days; range, 670 to 1,035). Group 2 included five infants, four with congenital lymphohematopoietic deficiencies and one with refractory acute lymphocytic leukemia (ALL). In these infants, busulfan and increased cyclophosphamide were substituted for TBI. Only the ALL patient received added T cells. Three patients engrafted: one has stable mixed chimerism, one relapsed with ALL, and one rejected the marrow. One patient had primary autologous recovery, while another failed to engraft. None developed GVHD. We conclude that, in this setting of HLA-disparate BMT with post-BMT antithymocyte globulin (ATG) and corticosteroids, DCE significantly depletes T cells from the marrow and that a defined number of T cells can be added without the occurrence of severe GVHD.
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PMID:Extended-cycle elutriation to adjust T-cell content in HLA-disparate bone marrow transplantation. 832 31

The combination of busulfan (Bu) and cyclophosphamide (Cy) has been found to be effective preparative therapy for patients treated with allogeneic bone marrow transplantation (BMT). We developed the BuCy2 regimen, which contains a lower dose of cyclophosphamide than the original BuCy regimen, in the hope of reducing regimen-related toxicities. We have studied the use of BuCy2 as preparation for allogeneic BMT in patients with acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma. In patients with acute myelogenous leukemia, the leukemia-free survival and regimen-related toxicity rates obtained in our study appear similar to those achieved with other preparative regimens, including those containing Cy and total body irradiation (TBI). BuCy2 is also an effective BMT preparative regimen in patients with acute lymphocytic leukemia and multiple myeloma. Treatment with BuCy2 results in a lower incidence of severe stomatitis and probably of interstitial pneumonia than does treatment with Cy/TBI, but hepatic veno-occlusive disease occurs more frequently in BuCy-treated patients. The incidence of veno-occlusive disease appears to be affected by agents used as prophylaxis for graft-versus-host disease. Compared with Cy/TBI regimens, BuCy treatment is likely to result in fewer delayed effects of treatment, such as impairment of fertility and second malignancies. Current clinical efforts are focusing on ways to improve the antileukemic activity of the BuCy preparative regimen and to reduce regimen-related toxicities.
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PMID:Allogeneic bone marrow transplantation for acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma following preparation with busulfan and cyclophosphamide (BuCy2). 834 74

A 33-year-old woman with AML (M4) resistant to chemotherapy received syngeneic marrow graft from her identical twin following high dose busulfan and etoposide. However, the relapse was confirmed on the 60th day after the procedure. Since she failed to achieve remission despite intensive chemotherapy, a second BMT from the same donor was performed following total body irradiation and high dose etoposide on the 126th day after the initial BMT. At this time, cyclosporine (1 mg/kg/day) was administered to induce graft-versus-host disease (GVHD). Skin rash appeared on the 18th day after the 2nd BMT, and biopsy from the rash on the 23rd day showed a typical picture of cutaneous GVHD (grade 2) and there was no evidence of viral infection. On the 36th day after the 2nd BMT, the patient died of veno-occlusive disease. Although graft-versus-leukemia effect in this patient could not be evaluated because of early death, the induction of GVHD with cyclosporine might be effective to reduce the relapse rate after syngeneic or autologous BMT. Further studies are required to confirm this effect.
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PMID:[Cyclosporine-induced graft-versus-host disease in a syngeneic bone marrow transplantation]. 845 Jun 5


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