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Biomedical subjects

W A Robinson

Publications and source records attributed to W A Robinson.

At least 19 recordsLinked to original sources
PubMed1992

Low-dose alpha-interferon treatment of chronic myeloid leukemia.

We treated 29 patients with chronic-phase and accelerated chronic myeloid leukemia (CML) with alpha-interferon in a dose of 2 mU/m2 given subcutaneously daily for 30 days and then three times per week. Most had received prior treatment. Three patients have had sustained hematologic and karyotypic remissions after a median of 22 months of treatment. Three further patients have had complete hematologic and partial karyotypic remissions. At a median follow-up of 48 months, the median survival has not been reached. This dose of alpha-interferon may induce sustained remissions even in pretreated patients and may prolong survival in CML.

Adult↗
PubMed1992

Breast metastases from malignant melanoma.

We review here 15 patients with cutaneous malignant melanomas metastatic to the breast. All but one were premenopausal females with a median age of 38 years. Most patients had a primary lesion on the upper extremities or trunk (80%), with only one patient having a lower extremity primary. The median interval between diagnosis of the primary and breast involvement was 33 months, with one patient developing breast involvement 11 years later, at the time of her second pregnancy. Five patients had bilateral breast involvement, and all had other sites of metastases at the time of diagnosis. The median survival after diagnosis of breast metastases was 10 months, portending a poor prognosis.

Adult↗
PubMed1992

Preferential chromosome 11q and/or 17q aberrations in short-term cultures of metastatic melanoma in resections from human brain.

Thirteen specimens of metastatic malignant melanoma resected from eight patients undergoing craniotomy were analyzed cytogenetically from short-term cultures. All patients had chromosome 1 aberrations, as did three of four patients with metastases only to extracranial sites. Both groups had variable involvement of chromosomes 3, 6, 7, and 8. Only those with brain metastases had 11q and/or 17q involvement in six of eight patients. In reported cases of nonbrain metastases, when chromosome 11 was involved, the short arm was usually deleted or replaced through translocation; on the contrary, in reports on patients with brain metastases, the long arm of chromosome 11 was deleted at q23 or was the recipient of a translocation at q23, and/or 17q was present as an isochromosome. These aberrations were similar to those found in the patients with brain metastases in this report. Two patients undergoing brain resections did not show 11q or 17q aberrations, one near diploid with t(10;19) and the other near hexaploid with few structural rearrangements. The neural cell adhesion molecule gene is located near 11q23, and the neural growth factor receptor is located near 17q21-q22. The relevance of these genes to brain metastases in melanoma is under investigation.

Brain Neoplasms↗
PubMed1992

A case-control study of late recurrence of malignant melanoma.

Late recurrence of malignant melanoma is uncommon but appears to be a growing problem. It is unclear whether late recurrence has a better prognosis than early recurrence. Since the answer may influence treatment, we compared recurrence sites and subsequent survival in 35 patients with disease-free intervals of 72 to 240 months (median: 127 months) with 35 case-controls who had relapse at 4 to 56 months (median: 26.7 months). The distribution of recurrence sites in early relapse was 66% in regional nodes or soft tissue and 34% in distant soft tissue or viscera. In late relapse, this distribution was 49% in regional nodes or soft tissue and 51% in distant soft tissue or viscera (no significant differences). Median survival for patients with early and late recurrences in regional nodes or soft tissue was 26 and 44 months, respectively (no significant differences); 5-year survival was 27% and 33%, respectively (no significant differences). Median survival was similar for early or late relapse in distant soft tissue or viscera (8 and 10 months, respectively), as was 5-year survival (0% and 6%, respectively). These results suggest that the metastatic pattern and survival after recurrence are similar for patients with early and late recurring melanoma.

Case-Control Studies↗
PubMed1991

Role of recombinant alpha-interferon in the treatment of advanced cutaneous malignant melanoma.

A total of 65 patients with advanced cutaneous malignant melanoma (MM) have now been treated with interferon alpha-2b (Intron A) at a dose of 10 million IU/m2 administered subcutaneously thrice weekly. Fifty-one patients were evaluable for response, and 4 of these (7.8%) achieved complete remission; 2 of these 4 remain so at 37 + and 54 + months. Six additional patients achieved a partial remission. All responders had subcutaneous, lymph node and/or pulmonary metastases only. In all responders, therapy was continued for a total of 12 months. The vast majority of patients experienced side effects, largely flu-like symptoms, mild leukopenia and mild hepatocellular dysfunction. No evidence of cumulative toxicity was observed. Our experience indicates that interferon alpha-2b is active in patients with advanced cutaneous MM.

Adult↗
PubMed1991

Single-dose murine monoclonal antibody ricin A chain immunotoxin in the treatment of metastatic melanoma: a phase I trial.

To determine the maximally tolerated dose of a ricin A chain-conjugated antimelanoma antibody (XomaZyme-Mel), 20 patients with metastatic melanoma were treated with escalating doses of the murine immunotoxin given as single intravenous infusion over 30 minutes. The starting dose was 0.6 mg/kg and was escalated in five groups to a maximum of 1.6 mg/kg. The maximally tolerated dose was 1.25 mg/kg as three of six patients treated at 1.6 mg/kg developed unacceptable toxicity. The dose-limiting toxicity consisted of profound fatigue, myalgias, and arthralgias. These occurred within 4 days and resolved in 7 to 10 days. Other non-dose-limiting toxicities encountered consisted of hypoalbuminemia, weight gain, peripheral edema, mild hypotension, and flu-like syndrome; the severity of these was also dose related. In addition, two allergic reactions occurred, one severe. There was one durable complete response of 12+ months' duration and one brief mixed response lasting 3 months. We conclude that the maximum tolerated single dose of XomaZyme-Mel is 1.25 mg/kg. Phase I studies evaluating 1.25 mg/kg given in multiple doses at 2- to 4-week intervals and phase II studies to determine the response rate of a single 1.25 mg/kg dose are warranted.

Adult↗
PubMed1979

Control factors of granulopoiesis in human serum.

The role of serum factors in the modulation of production of colony-stimulating activity (CSA) has been investigated. A factor has been described, and partially characterized, in human serum that has the capacity to stimulate increased synthesis and release of CSA by human mononuclear cells (MNC). MNC RNA and protein synthesis are required to demonstrate this effect of serum, but DNA synthesis and mitotic division are not required. The factor in serum resulting in this effect is a heat-labile protein with a molecular weight slightly greater than that of CSA.

Animals↗
PubMed1979

Macrocytic anemia, thrombocytosis and nonlobulated megakaryocytes: the 5q-syndrome, a distinct entity.

The clinical, hematologic and histologic characteristics of six patients with refractory anemia with deletion of the long arm of chromosome No. 5 are described. These patients had a distinct hematologic picture with macrocytic anemia of mild to moderate severity, normal to low leukocyte count and increased platelet count. The long arm of chromosome No. 5 was deleted in the majority of bone marrow metaphases. The main cause of anemia was underproduction with decreased erythroid precursors in the bone marrow and no increase in peripheral blood reticulocytes. Two of five patients responded transiently to the administration of androgens. In vitro evaluation of the bone marrow growth pattern in semisolid agar culture system was performed in three patients and was found to be normal and distinct from that in patients with preleukemia. In a follow up of up to five years, no patient had changed hematologically and in none had leukemia developed. The 5q-syndrome is a distinct hematologic entity and probably more common than hitherto realized. This diagnosis may have therapeutic and prognostic implications.

Adult↗
PubMed1979

Current concepts of abnormal stem cell proliferation in human disease.

Using acute myeloid leukemia as an example, the concept of abnormal hematopoietic stem cell production has been examined. It is concluded that the major problem does not lie in humoral regulators, either stimulators or inhibitors, of stem cell production but in intrinsic cellular defects which do not allow cells to respond to these materials. The nature of the stem cell defects has not been defined. Similar mechanisms appear to exist in other human hematopoietic disorders in which abnormal stem cell proliferation is a major feature.

Animals↗
PubMed1979

Chronic myelocytic leukemia (CML): failure to detect residual normal committed stem cells in vitro.

Granulocytic colonies grown in culture from marrow and peripheral blood from five patients with Ph1-positive CML and heterozygous at the G-6-PD locus were analyzed for G-6-PD in order to identify CFU-C that do not arise from the CML clone. The patients had both B and A enzymes in normal tissues, but their CML clones typed as B. Whereas about 50% of colonies from normal subjects heterozygous as the G-6-PD locus show type-A G-6-PD and 50% type B, only two of the 1308 colonies from the CML patients had type-A G-6-PD. These data provide little evidence for persistence of normal committed stem cells in CML, a finding in contrast to that made previously in polycythemia vera, another clonal stem cell myeloproliferative disorder.

Adult↗
PubMed1979

Recovery of CFU-C after freezing of normal and leukemic human bone marrow.

Studies have been carried out to determine the viability of leukemic and normal human bone marrow, cryopreserved in liquid nitrogen at -196 degrees C, using changes in total cell numbers and granulocyte colony forming ability in vitro. These studies have shown that there is considerable variability in the recovery of CFU-C from individual specimens. When the overall recovery, in all patients, is taken into account, there is a gradual decline in CFU-C numbers to about 60% after 24 months of freezing. CFU-C recovery is closely correlated with recovery of total cell numbers.

Bone Marrow Cells↗
PubMed1979

Autologous bone-marrow and peripheral blood buffy coat cell infusion in the treatment of chronic myeloid and acute leukemia.

Autologous marrow infusion has been attempted in three patients with chronic myeloid leukemia (two in blast crisis, one with severe myelofibrosis and pancytopenia) and one patient with acute lymphatic leukemia. One patient with blast crisis of CML expired prior to marrow infusion. One patient with myelofibrotic phase of CML is alive seven months post marrow infusion. The other two patients expired 6 and 16 days post marrow infusion. Bone-marrow repopulation is feasible in the face of severe myelofibrosis.

Adult↗
PubMed1979

Liquid storage of bone marrow.

A program of nonfrozen autologous bone marrow rescue was used to treat patients with refractory nonhematological neoplasms. In vitro storage of bone marrow cells and CFU-C suggests that storage at 4 degrees or 10 degrees for periods up to five days can be undertaken with only minor loss of CFU-C. However, since the loss occurred in a gradual fashion, shorter duration of storage would probably be better. Hematological recovery after high dose chemotherapy occurred faster in patients given more CFU-C and those with shortest duration of storage prior to reinfusion.

Bone Marrow↗