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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High dose cytarabine (HDARAC) therapy is used increasingly to treat hematologic malignancies. Recent data indicate that HDARAC at doses of 2-3 g/M2 every 12 hr x 10-12 doses is of comparable or greater efficacy in remission induction as standard doses of cytarabine in acute myelogenous leukemia. HDARAC can also produce remissions in individuals resistant to conventional doses. HDARAC-containing regimens are reported to result in substantially higher long-term, disease-free survival than previous approaches to post-remission therapy, but this has not yet been confirmed in controlled trials. HDARAC is also active in acute lymphocytic leukemia. Because intravenous HDARAC achieves high levels in the spinal fluid, it is useful to treat central nervous system leukemia and may provide adequate CNS prophylaxis in acute lymphocytic leukemia. HDARAC is reported to be active in advanced non-Hodgkin lymphomas and chronic myelogenous leukemia in acute phase; optimal use in these settings is under study. HDARAC has also been combined with other drugs. Randomized trials are needed to determine whether these combinations are more effective than HDARAC alone. Apart from potent myelosuppression, the dose-limiting toxicity of HDARAC is cerebellar damage. This occurs with increased frequency in patients greater than 50 years old. HDARAC is active in hematologic malignancies and may further improve therapeutic results if combined with other drugs.
Leukemia 1988 May
PMID:High dose cytarabine: a review. 328 15

Graft-versus-host disease prevention was attempted in 35 consecutive patients with hematological malignancy who received bone marrow from an HLA match sibling donor who was depleted of T cells ex vivo. Five of the first 8 patients who received cyclophosphamide 60 mg/kg on 2 consecutive days followed by fractionated total body irradiation (TBI) (6 x 2 Gy) had graft failure. The subsequent 27 patients had received an extra fraction of TBI (7 x 2 Gy), and only one failed to have stable engraftment. There were no differences in nucleated cell dose, granulocyte-macrophage colony-forming units, or T cell numbers given to the two groups. Neutrophil but not platelet regeneration of those patients who successfully grafted was slower than in a group of historical controls receiving unmanipulated marrow. Significant graft-versus-host disease was prevented with no increase in relapse rate. We suggest that engraftment can be reliably achieved by augmenting the TBI conditioning in recipients of T cell-depleted matched allogeneic bone marrow.
Leukemia 1988 May
PMID:Prevention of graft-versus-host disease by ex vivo T cell depletion: reduction in graft failure with augmented total body irradiation. 328 16

We treated 73 patients with hematologic malignancies in first complete remission (acute lymphoblastic leukemia = 23 patients; acute non-lymphoblastic leukemia = 25 patients; chronic myelogenous leukemia in first chronic phase = 20 patients, and high grade lymphoma = five patients) with a uniform preparative regimen consisting of fractionated total body irradiation (1,320 cGy) and high dose cyclophosphamide (100 mg/kg), followed by allogeneic bone marrow transplantation. By radiation dosimetry we demonstrated that the calculated doses were delivered accurately and reproducibly. Actuarial survival rates (+/- SEM) in complete remission were as follows: Acute lymphoblastic leukemia = 74 +/- 9%; acute nonlymphoblastic leukemia = 50 +/- 11%; and chronic myelogenous leukemia = 55 +/- 11%. Actuarial relapse rates for these three diagnoses were 19 +/- 9%, 17 +/- 11%, and 0% respectively. Three of the five lymphoma patients are alive in complete remission at 22+, 28+, and 54+ months. Overall probability of survival for the 73 patients was 59 +/- 7%. Interstitial pneumonia, usually associated with cytomegalovirus infection and graft-versus-host disease, and relapse of the underlying malignancy were the major causes of death.
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PMID:Fractionated total body irradiation and high dose cyclophosphamide: a preparative regimen for bone marrow transplantation for patients with hematologic malignancies in first complete remission. 329 91

Serum ferritin levels were monitored in nine patients with acute lymphoblastic leukemia (ALL), nine patients with acute nonlymphoblastic leukemia (ANLL), four patients with chronic myelogenous leukemia (CML), three patients with non-Hodgkin's lymphoma (NHL), and three patients with severe aplastic anemia (SAA) undergoing bone marrow transplantation (BMT) for hematologic malignancies or aplastic anemia. Serum ferritin analysis was performed before and after BMT at monthly intervals and/or according to the clinical condition of the patient. Serum ferritin increased considerably during the first 3 months following BMT and then decreased in patients with an uncomplicated course. Ferritin levels in the serum of patients who had undergone BMT decreased gradually when complete remission was achieved, but increased with any clinical complication. Thus, elevation of serum ferritin concentration was predictable for clinical complications and for relapse. Patients with acute leukemia with serum ferritin levels above 400 micrograms/l at time of BMT had a risk of relapse within 1 year, triple that patients with lower ferritin levels. All patients who underwent BMT to treat severe aplastic anemia have completely recovered. Accordingly, following an initial increase after BMT, serum ferritin levels returned to normal and remained so in line with the patients' good clinical condition. The findings indicate that serum ferritin yields useful information in the clinical evaluation of patients undergoing BMT.
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PMID:Serum ferritin in patients undergoing bone marrow transplantation. 330 Sep 50

Sixteen patients with hematological malignancy received cyclophosphamide (120 mg/kg), fractionated total body irradiation (12 Gy), oral cyclosporin, and an HLA-identical sibling marrow transplant depleted of T cells by incubation with the monoclonal antibody anti-HuLy-m1 (CD2) and rabbit complement with (five patients) or without (11 patients) anti-HuLy-m8). These 16 patients were compared historically to 84 patients with hematological malignancy receiving cyclophosphamide (120 mg/kg), fractionated total body irradiation (12 or 14 Gy), oral cyclosporin, and unmanipulated HLA-identical sibling marrow, for parameters of engraftment and graft-versus-host disease (GVHD). Graft failure occurred in one of the 16 T-cell depleted recipients and in one of the 84 nondepleted recipients. Engraftment was slightly but significantly slower in the T-cell depleted group and bacterial infections significantly more frequent and severe than in the unmanipulated group. There was a suggestion that the severity of acute GVHD was reduced in those receiving T depleted marrow. Randomized trials will be necessary to determine if marrow T-cell depletion results in superior long-term leukemia-free survival.
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PMID:A comparative study of T-cell depleted and non-depleted marrow transplantation for hematological malignancy. 330 40

Having reviewed conventional chemotherapy of acute leukaemia in the preceding article, a discussion of high dose chemotherapy in haematological malignancy is presented. The indications and side-effects of high dose methotrexate, ifosfamide and etoposide (VP-16) are summarized in tabular form. The toxicity and effectiveness of high dose cytosine arabinoside in the treatment of refractory acute leukaemia is discussed. The use of high dose melphalan to treat patients with multiple myeloma or other tumours is reviewed. The most widely used cytoreductive regimes in bone marrow transplantation, high dose busulphan, high dose cyclophosphamide and total body irradiation are described.
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PMID:Therapeutic progress--review XXVII. High dose chemotherapy in haematological malignancy. 330 28

Twenty-nine of 172 patients (17%) who received an allogeneic bone marrow transplant (BMT) from histocompatible sibling donors for hematologic malignancies were mixed hematopoietic chimeras; ie, they had a mixture of donor and host hematopoietic or lymphohematopoietic cells at greater than or equal to 14 days after transplantation. Twenty-four of the 29 mixed chimeras (83%) have remained in continuous complete remission for up to 116 months (greater than 9 years) following BMT. Four of the 29 patients (14%) have had recurrent leukemia, and 7 of the 29 (24%) have had moderate or severe graft-v-host disease (GVHD). Twelve of these 29 patients have persisted as stable mixed chimeras for greater than or equal to 2 years after BMT, whereas other patients converted to all donor-type hematopoiesis. The incidence of mixed chimerism was independent of the pretransplant regimen, the donor or recipient age (less than 20 v greater than 20 years), remission status (first complete remission of acute leukemia and first chronic phase of chronic myelocytic leukemia v later stages of disease), and type of leukemia. Our data indicate that mixed hematopoietic chimerism is not rare after BMT for hematologic malignancies and that its presence is compatible with long-term disease-free survival. Prospective studies of mixed chimerism after BMT are warranted to achieve better understanding of its biologic importance.
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PMID:Mixed hematopoietic chimerism following bone marrow transplantation for hematologic malignancies. 331 Dec 1

Acute nonlymphocytic leukemia (ANLL) is a heterogeneous group of hematologic malignancies caused by a clonal proliferation of primitive myeloid cells. 30 Infiltration of the bone marrow by these cells causes impairment of normal hematopoiesis and results in anemia, granulocytopenia, and thrombocytopenia. Recent progress in bone marrow culture techniques, cytogenetics, and immunology have contributed to a better understanding of the pathophysiology of ANLL. Major therapeutic advances have also occurred because of improved supportive care and carefully designed prospective and randomized clinical trials. This article presents the current knowledge of the diagnosis and management of ANLL.
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PMID:Acute nonlymphocytic leukemia in children. 332 73

One-hundred-and-forty-three patients with haematological malignancy or severe aplastic anaemia received HLA-identical sibling bone marrow transplants. In 111 of these patients who had haematological malignancy and who were prepared for transplant with cyclophosphamide 120 mg/kg and fractionated total body irradiation 12-14 Gy, the incidence of haemorrhagic cystitis and hepatic veno-occlusive disease was 13% and 3%, respectively. In contrast, the incidence in 15 leukaemic patients prepared for transplant with chemotherapy regimens containing high-dose busulphan was 47% and 20%, respectively (p less than 0.001). Two patients in this latter group who developed fatal veno-occlusive disease had chronic myeloid leukaemia and had received long-term low-dose busulphan pre-transplant. Neither complication occurred in 26 patients prepared by cyclophosphamide alone (20 patients with severe aplastic anaemia) or with cyclophosphamide and melphalan (six patients with leukaemia). The regimen of busulphan 16 mg/kg in combination with cyclophosphamide 120 mg/kg was associated with a short duration of total leucopenia with a significantly higher leucocyte count on the day of marrow transplant compared to other regimens. Furthermore, oro-pharyngeal mucositis was not severe even when methotrexate was utilised as post-transplant prophylaxis for graft-versus-host disease. Thus, while the busulphan-cyclophosphamide regimen appeared useful, we suggest that (1) high-dose busulphan should not be used as a preparative regimen for patients previously exposed to busulphan, and (2) bladder irrigation (as well as intravenous hydration) is necessary to minimise haemorrhagic cystitis in patients given regimens that incorporate high-dose busulphan.
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PMID:Preparative regimens for marrow transplantation containing busulphan are associated with haemorrhagic cystitis and hepatic veno-occlusive disease but a short duration of leucopenia and little oro-pharyngeal mucositis. 333 86

Bone marrow necrosis is a poorly understood and frequently an unrecognized finding in routine bone marrow biopsies. Previous reports indicate the incidence of bone marrow necrosis ranges from 0.5 percent (rare) to approximately one-third of all bone marrow biopsies examined. Our studies indicate that the presence of bone marrow necrosis depends on the clinical condition of the patient. Overall, our incidence of bone marrow necrosis was 37 percent of the bone marrow biopsies examined. Of these, 26.4 percent was mild. 7.5 percent moderate, and 3.1 percent severe necrosis. The mechanism in most cases had an identifiable underlying etiology such as a malignancy, or vascular or cytotoxic damage, with a small percentage being unexplained. Bone marrow necrosis is seen across a wide range of conditions, including sickle cell diseases, AIDS, leukemia, lymphoma, metastatic carcinoma, anemia, sepsis, and other systemic diseases. Patients at the extremes of age, less than 20 years and greater than 70 years, usually demonstrate only small foci of necrosis (Grade I). Moderate (Grade II) and severe (Grade III) bone marrow necrosis are often associated with life threatening illnesses, with most of these being hematologic malignancies or bone marrow metastases. The prognosis associated with bone marrow necrosis seems to be dependent on the underlying primary clinical condition regardless of the degree of necrosis observed.
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PMID:Bone marrow necrosis: an entity often overlooked. 338 56


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