Mycosis fungoides: subcutaneous and visceral tumors, orbital involvement, and ophthalmoplegia.

A patient with advanced severe mycosis fungoides presented several unusual features, including prominent lesions of the palate and tongue and an orbital tumor with exophthalmos and ophthalmoplegia. A hitherto undescribed feature was the development of multiple, massive subcutaneous tumors unrelated to the dermis or to lymph nodes, and large tumors in the connective tissues of the buttock, flank, and retroperitoneum. The usual sites of extracutaneous dissemination of mycosis fungoides--lymph nodes, spleen, liver, lungs, and blood--were not demonstrably involved. This may be a new pattern of dissemination for this disease. Of practical importance is the immediate and complete relief of exophthalmos and ophthalmoplegia that was obtained with emergency radiotherapy.

Hairy-cell leukemia: induction of complete remission with pentostatin (2'-deoxycoformycin).

Two men with advanced but previously untreated B cell hairy-cell leukemia were treated with low doses of pentostatin (2'-deoxycoformycin) in intermittent courses. There was prompt clearance of hairy cells from the blood, regression of splenomegaly and lymphadenopathy, and correction of anemia, thrombocytopenia, and granulocytopenia. Side effects were tolerable and myelosuppression was not observed. Both patients achieved complete remission documented by bone marrow aspiration and biopsy and radionuclide scans of liver and spleen. They remain in complete remission nine and six months, respectively, after their last treatment. Pentostatin (Warner-Lambert, Ann Arbor, Mich) is highly active in hairy-cell leukemia and merits more extensive evaluation in this disease. A woman with hairy-cell leukemia has begun treatment with pentostatin, and at ten weeks there is disappearance of gross splenomegaly and clearance of hairy cells from the blood. Bone marrow studies have not yet been repeated.

Pentostatin induces durable remissions in hairy cell leukemia.

Fifty patients with hairy cell leukemia were treated with pentostatin (2'-deoxycoformycin; dCF) for a median of 3 months; 32 (64%) patients achieved complete remission (CR), and 10 (20%) patients achieved partial remission (PR), for an overall response rate of 84%. After reaching maximal response, no maintenance therapy was administered. The median duration of follow-up is now 39 months, and only four of 32 patients in CR and two of 10 patients in PR have relapsed. dCF therapy produces durable long-term, disease-free survival in patients with hairy cell leukemia.

The treatment of hairy cell leukemia with 2'-deoxycoformycin: results in India and in the United States.

We treated 11 patients (nine men and two women) with hairy cell leukemia with low doses of pentostatin (2'-deoxycoformycin). As of January 1987, 10 patients (91%) were in complete remission (CR) and one (9%) was in partial remission. Thus, the overall response rate was 100%. Maintenance therapy was not given once CR was attained, but no patient in CR relapsed: remission durations were from 40+ to 9+ months. For hairy cell leukemia, pentostatin is a better treatment than splenectomy and probably is superior to interferon, but further studies are needed to better define its role in this disease.

Inferior vena cava obstruction. A complication of prostate cancer.

Inferior vena cava (IVC) obstruction, manifested as bilateral, asymmetric, asymptomatic, pitting leg edema and scrotal swelling, developed in two patients with advanced prostatic cancer. Radiological confirmation was obtained in both patients. Inferior vena cava obstruction was the initial manifestation of disease progression and occurred in patients who were ambulatory without evidence of congestive heart failure or concurrent estrogen therapy. Early IVC contrast study is indicated in similar patients in whom asymptomatic bilateral leg edema of obscure origin develops.

The role of pentostatin (2'-deoxycoformycin, dCF) in the management of lymphoproliferative malignancies.

Laboratory and clinical data relating to the use of 2'-deoxycoformycin in human disease are reviewed. Pentostatin is an inhibitor of adenosine deaminase, an enzyme that is important for purine metabolism, but more than one mechanism may be involved in its cytotoxic action. Early studies with dCF employed large doses and for the most part were conducted in patients with acute lymphocytic leukaemia: responses were brief and relatively few, and severe renal, hepatic, and central nervous system toxicity were encountered, leading to temporary abandonment of clinical trials. More recently, it has been shown that dCF is effective in much smaller doses, with considerably less toxicity. It has proved to be more effective in low-grade lymphoid malignancies (chronic leukaemias, indolent lymphomas) than in more undifferentiated neoplasms (acute leukaemias, lymphoblastic and immunoblastic lymphomas), and is outstandingly effective in hairy cell leukaemia, both as initial therapy and after failure of splenectomy and interferon. Pentostatin is profoundly immunosuppressive: generally this is considered a disadvantage but its potential therapeutic exploitation merits investigation. Despite extensive knowledge of its biochemical effects, the optimal dose regimen of dCF and the value of combining it with purine antagonists remain to be defined.

Clinical manifestations of chronic granulocytic leukemia.

CGL is a highly specific disease that is defined by strict hematologic parameters that include a pathognomonic differential leukocyte count. Usually CGL is accompanied by the presence, in bone marrow cells, of the Ph chromosome, the first chromosomal anomaly to be regularly associated with a human neoplastic disease. CGL is predominantly a disease of the productive middle years of life, which maximizes its adverse impact on family life and family economics. The disease is of worldwide distribution and there is a slight male preponderance. The disease is characterized by an initial chronic phase when it behaves as a differentiated neoplasm and responds very well to simple, nonintensive therapy. After a variable interval, CGL undergoes metamorphosis to a refractory phase that responds poorly or sometimes not at all to therapy, even when this is intensive. At the stage of metamorphosis a great variety of clinical and hematologic pictures occur, and CGL may mimic a myeloproliferative disease, a myelodysplasia, a subacute leukemia, AML, or ALL. The old concept of an abrupt, explosive transition from the chronic phase to a so-called blastic crisis is incorrect: this rarely occurs and in most patients who are carefully followed, CGL is observed to undergo two or more stepwise evolutions, eg, from chronic phase to an accelerated myeloproliferative phase to a phase that resembles AML. Many patients with CGL conform to an established pattern of clinical features. There is a history of insidious symptoms of anemia and of splenomegaly. The physical signs are those of pallor and marked splenomegaly, while the hematologic findings are of moderate anemia, moderate thrombocytosis, and a marked granulocytic leukocytosis with a specific differential count. The radiologic findings are typically normal. Diagnostic difficulty seldom arises with this classic presentation. The patient who is detected at an early stage of CGL may lack the history, physical signs, and fully developed hematologic picture of CGL. Before the availability of cytogenetic studies, the diagnosis could only be established with confidence by observing the patient until the typical features of the disease emerged. Also considered are the less frequent but important atypical presentations of CGL. The symptoms and complaints, findings on examination, complications and hematologic findings may depart from the typical case in a bewildering variety of ways, so that the diagnosis may be difficult, indeed, CGL is generally not the initial diagnosis that is made. When the patient with CGL has received treatment, it is usual for he or she to become asymptomatic, with no abnormal physical signs.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute lymphoblastic leukemia of Burkitt's type (L-3 ALL) lacking surface immunoglobulin and the 8;14 translocation.

A 25-year-old man developed acute lymphoblastic leukemia, morphologically of Burkitt's type (L3-ALL, F.A.B. classification) but with immunologic and cytogenetic features not previously reported. The leukemic blasts were B1+, CALLA+, OKT3-, and OKT11-. Surface immunoglobulin and cytoplasmic IgM were not detected, but cytoplasmic IgG lambda was present. Karyotypic analysis of 20 metaphases was normal at presentation but abnormal after relapse. At that time, the predominant karyotype was 47XY, 1q-, 7q-, 12p-, M1. This case illustrates the following: (1) Burkitt cell morphology may accompany some uncommon pre-B-cell lymphoblastic leukemias, and (2) rearrangements involving chromosomes 14, 2 or 22 may not be found in all cases of L-3 ALL.

Neutrophil alkaline phosphatase score in chronic granulocytic leukaemia: effects of splenectomy and antileukaemic drugs.

Staining with naphthol AS phosphate and Fast Blue BB salt has been used for the estimation of neutrophil alkaline phosphatase (NAP) scores in patients with chronic granulocytic leukaemia (CGL). The very low scores found at diagnosis rise when the disease is treated, and there is some inverse correlation between the NAP score and the absolute neutrophil count. Patients treated intensively developed high NAP scores. Elective splenectomy performed during the chronic phase of CGL is followed by a pronounced but transient neutrophilia and a concurrent striking rise in the NAP score. Similar changes were observed in patients without CGL who underwent splenectomy. These observations can be explained by assuming that newly formed neutrophils in CGL have a normal content of NAP but are rapidly sequestered in non-circulating extramedullary pools, whereas the circulating neutrophil with a typically low NAP content is a relatively aged cell which has lost enzyme activity. In subjects with or without CGL, removal of the spleen, a major site of such pooling, temporarily permits the circulation of newly formed neutrophils but eventually other organs assume the sequestering functions of the spleen. Thus the aberrations of NAP score seen in CGL might be attributable not to an intrinsic cellular defect but to an exaggeration of the granulocyte storage phenomena which also occur in subjects without CGL.

Megakaryoblastic transformation of chronic granulocytic leukaemia. An electron microscopy and cytochemial study.

Morphological, cytochemical, and ultrastructural electron microscopic (EM) studies were performed on blood and bone-marrow cells of case of Ph1-positive chronic ganulocytic leukaemia in megakaryocytic acute transformation. The entire leukaemic cell population was found to consist and of megakaryoblasts and megakaryocytes. Intermediate stages of maturation between blasts and micromegakaryocytes were observed at EM level.

Chronic granulocytic leukemia.

This article reviews the definition, etiology, epidemiology, cytogenetics, and diagnosis of chronic granulocytic leukemia (CGL). There is detailed consideration of clinical and laboratory findings, the natural history of CGL, and the selection of therapy at different stages of the disease. The roles of bone marrow transplantation and of newer experimental therapeutic approaches are discussed.

Treatment of advanced refractory lymphomas with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (the BBVDD regimen). An ECOG pilot study.

Forty-four patients with relapsed, refractory malignant lymphomas (12 Hodgkin's disease, 32 non-Hodgkin's lymphoma) were treated with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (BBVDD regimen). Patients had failed at least one, and frequently two, chemotherapy regimens before admission to the study. Of the patients with Hodgkin's disease, 2 (17%) achieved complete response (CR), and 3 (25%) attained a partial response (PR) for an overall response rate (CR + PR) of 42%. Among the patients with non-Hodgkin's lymphoma there were 6 CR (19%) and 12 PR (37%), for an overall response rate of 56%. Median durations of response ranged from 2.5 months for nodular non-Hodgkin's lymphoma in PR to 28.5 + months for Hodgkin's disease in CR. In these heavily pretreated patients, the incidence of toxic effects was grade 3 (48%), grade 4 (23%), grade 5 (2%). The one death (grade 5 toxicity) was attributed to pulmonary impairment due to bleomycin. BBVDD is a moderately effective regimen for the palliation of patients with refractory lymphomas and merits further study.

Chronic granulocytic leukaemia in pregnancy.

In an era when the use of ionizing radiations for the treatment of chronic granulocytic leukaemia has largely been supplanted by therapy with busulphan or other drugs, there still exist situations where irradiation is the preferred method of initial treatment. One such situation is the unusual conjunction of chronic granulocytic leukaemia and pregnancy. Chronic granulocytic leukaemia (CGL) was diagnosed in two young women during early pregnancy as a result of routine blood examinations. Both responded satisfactorily to splenic irradiation with shielding of the uterus. The pregnancies proceeded uneventfully and each was successfully delivered of a normal and subsequently healthy baby. Both mothers later underwent elective splenectomy during a period of satisfactory haematological control: no operative or post-operative complications occurred. Although both patients have shown some thrombocytosis and peripheral blood basophilia since splenectomy, they remain well 58 and 28 months after diagnosis and 30 and 18 months after splenectomy.

Case report: cutaneous manifestations of cryptococcosis.

Cutaneous cryptococcosis usually is associated with concurrent systemic infection and actually may develop before clinical manifestations of cryptococcal meningitis become apparent. It is rare for a cryptococcal infection to be localized only to the skin. A case of cutaneous cryptococcosis is described in an immunocompromised patient who initially had a rash and a positive serum cryptococcal antigen titer, but no central nervous system involvement. The papular pustular skin lesions disappeared after 8 weeks of therapy with amphotericin B, which was stopped secondary to progressive azotemia. Less than 2 months after therapy, the skin lesions recurred, again without evidence of systemic disease. Treatment with oral fluconazole resulted in a gradual resolution of the cutaneous lesions. The pathogenesis of cryptococcosis is discussed, with emphasis on the management of cutaneous cryptococcosis.

Can MRI of the knee affect arthroscopic practice? A prospective study of 58 patients.

We made a prospective study of 58 patients with suspected internal derangement of the knee. They were examined by magnetic resonance imaging using 3-D gradient echo intermediate-weighted studies before having an arthroscopy. The preoperative clinical assessment was found to have a diagnostic sensitivity of 77% and a specificity of 43%, compared with 100% and 63% respectively for magnetic resonance imaging. Comparison of magnetic resonance imaging and arthroscopy confirmed the accuracy of magnetic resonance imaging in the diagnosis of internal derangement but the results for articular cartilage lesions were much less good, with a sensitivity of only 18% but a specificity of 100%. Acceptance of the magnetic resonance imaging findings could have resulted in a 29% reduction in the number of arthroscopies without missing any significant meniscal lesion.