Ho Nieweg

Successful chemotherapy with deoxycoformycin in adult T-cell lymphoma-leukaemia

A patient from the Caribbean area with active T‐cell lymphoma‐leukaemia was primarily treated with deoxycoformycin (DCF), 5 mg/m2 i.v. on 3 consecutive days, followed by 5 mg/m2 i.v. weekly. A complete remission was attained and maintained during several weeks with DCF. A single consolidation course with other cytostatics was then given. The patient continues in complete remission without further therapy, 24 months after diagnosis, 17 months after the last cytostatic drugs. T‐cell lymphoma‐leukaemia has a bad prognosis with conventional anti‐lymphoma therapy but was exquisitely sensitive to DCF in this patient.

THE INFLUENCE OF L-ASPARAGINASE THERAPY ON THE FIBRINOLYTIC SYSTEM

Summary. Fibrinolytic factors were assessed during L‐asparaginase administration, to study whether their changes may predispose to a haemorrhagic or thrombotic diathesis. The total level of α2‐antiplasmin declined, as well as the ratio of the plasminogen‐binding form of α2‐antiplasmin to the non‐plasminogen‐binding form. After cessation of L‐asparaginase administration, the ratio increased to 1.6 times that of the pretreatment value. These data indicate that the plasminogen‐binding form of α2‐antiplasmin is the form primarily synthesized in vivo. L‐Asparaginase therapy reduced plasma levels of plasminogen and histidine‐rich glycoprotein (HRG) and influenced the equilibrium between HRG, plasminogen and HRG‐plasminogen complex, with a more pronounced decrease of plasminogen (62%±8) and HRG (76%±11) in comparison to the free‐plasminogen levels (51%±6). α2‐Macroglobulin was only slightly influenced by L‐asparaginase and may consequently play a more pronounced role in inhibition. This is suggested by moderate declines in functional tests of plasmin, urokinase and tissue activator inhibition by patients plasma, and by the ratio of inhibition of these enzymes over α2‐antiplasmin. Thus the bleeding tendency described during L‐asparaginase therapy can be ascribed not only to a temporary deficiency of coagulation factors but also to temporary α2‐antiplasmin deficiency.

SPECIFIC LYMPHOCYTE STIMULATION BY PURIFIED, HEAT-INACTIVATED HEPATITIS-B ANTIGEN

The ability of purified, heat-inactivated hepatitis-B antigen (HBAg) to stimulate sensitized lymphocytes in vitro was investigated with the lymphocyte stimulation test on lymphocytes from three groups of individuals. Stimulation was minimal in the lymphocytes of two out of 15 normal controls, whereas lymphocytes from nine out of 12 patients who had recovered from hepatitis B showed stimulation, as did lymphocytes from five out of 12 laboratory technicians who had been regularly exposed to HBAg but who had no history of hepatitis or signs of it in the previous two years. No differences were observed in the responses to phytohaemagglutinin of lymphocytes from persons in the three groups. HBAg and HBAg inactivated by heat were shown in immunodiffusion to be immunologically identical. Inactivated HBAg stimulated antibody production in guinea-pigs. These findings suggest that not only humoral but also cell-mediated immunity might be induced by vaccination with purified, heat-inactivated HBAg.

VINDESINE THERAPY IN MELPHALAN-RESISTANT MULTIPLE-MYELOMA

Abstract Vindesine, a new vinca alkaloid, was administered in thirteen patients with advanced multiple myeloma (stages IIIA and IIIB ), resistant to alkylating agents. Eleven patients received two complete courses and could be evaluated. Six patients ( 55% ) showed objective improvement. This was indicated by a decrease of greater than 50% of pretreatment myeloma protein serum levels, normalization of elevated serum calcium levels, and improvement of haemoglobin concentration and renal function. Neutropenia of short duration, mild paraesthesias and alopecia were noted as side effects.

The significance of the aminoterminal propeptide of type III procollagen in paroxysmal nocturnal haemoglobinuria and myelofibrosis.

The level of the aminoterminal propeptide Col 1–3 of type III procollagen (PC-III) was determined in patients with paroxysmal nocturnal haemoglobinuria (PNH) and primary myelofibrosis (PMF), to study whether PC-III can be used as a parameter for the rate and/or degree of bone marrow replacement with collagen. Normal PC-III levels were found in PNH (6.6±1.1 μg/l; N: 8.6±1.8 μg/l), while significantly increased levels were found in PMF (24.8±2.2 μg/l).During a follow-up of 1 year, a slight increase of 2 μg/l occurred in three patients with a stable fibrosis, while one patient with more active disease demonstrated an increase of 25 μg/l. Treatment with acetylsalicylic acid led to a decline of PC-III as well as β-thromboglobulin level, although normalization did not occur. It was demonstrated by means of gel filtration that the antigens related to the PC-III peptide were heterogenous, and that in PMF at least two main peaks were present, with molecular masses equal to and smaller than PC-III peptide.These data demonstrate that the radioimmunoassay cannot be used for the quantitative determination of PC-III; nevertheless it gives some insight in the process of bone marrow fibrosis.

Immunological responsiveness against two primary antigens in untreated patients with Hodgkin's disease☆

Abstract The immune responses against two primary antigens, dinitrochlorobenzene (DNCB) and α-haemocyanin of Helix pomatia (α-HPH) were studied in untreated, meticulously-staged patients with Hodgkins disease and compared with those in control subjects of the same age group. Significantly more patients with the localized and the disseminated form, stages II, III and IV, and patients with nodular sclerosis, mixed cellularity and lymphocytic depletion had low DNCB sensitization grades (DNCB-scores). Antibody production to α-HPH was normal in all stages except in 2 out of 6 patients with stage IV, while significantly more patients with Hodgkins disease showed reduced lymphocytic stimulation by α-HPH following immunization. A close correlation was observed between the DNCB-score and in vitro lymphocyte stimulation by α-HPH following immunization. This may indicate that inability to produce sensitized T-lymphocytes plays an important role in the impairment of cell mediated immunity in Hodgkins disease. Although DNCB sensitization and in vitro lymphocyte stimulation by α-HPH were impaired in patients with stages II, III and IV as a group, several patients even with stages III and IV or with the disseminated form of Hodgkins disease showed normal cell-mediated immunity with these parameters.

Abnormal cells in the peripheral blood of patients with Hodgkin's disease. II. Ultrastructural studies.

The investigation of cells larger than normal in the peripheral blood of patients with Hodgkins disease by electron microscopy revealed, besides cells of the granulocytic series and parts of megakaryocytes, four other categories. The cells of the mononuclear phagocytic system could easily be recognized. The so‐called immunoblasts seen in light microscopy as dark basophilic lymphoid cells apparently consist of cells from B‐ as well as T‐cell origin, according to their ultrastructural characteristics. All these cells could also be found in nine healthy control persons, two patients with cytomegalovirus disease and two with reticulosarcoma.

Fine Structure of the Bone Marrow Sinusoidal Wall in Idiopathic and Drug-Induced Panmyelopathy

Ultrastructural studies of the bone marrow sinusoids showed no essential difference between the sinusoidal wall of patients suffering from panmyelopathy – idiopathic or drug-induced – and from control

ENDOTOXIN IN PAROXYSMAL NOCTURNAL HAEMOGLOBULINURIA (PNH)

known that spontaneous recovery may also occur. The role of lithium carbonate in the treatment of pancytopenia could only be assumed to have a beneficial effect. Therefore, as stressed at the meeting on Chloramphenicol Induced Aplasia held in Milan (Ferrari, 1980; Najean, 1980), we can postulate that this particularly pharmacological trial with lithium carbonate improved myelopoiesis in our patient. It seems worth investigating further the therapeutic action of lithium.

Monoclonal immunoglobulins with affinity for platelets and their relationship to malignant lymphoma

Monoclonal immunoglobulins with affinity for platelets were detected in the blood of seven patients. Two of these had thrombocytopenia and non‐Hodkins lymphoma (NHL). One patient had thrombocytopenia and possibly incipient NHL. The other four patients had pseudothrombocytopenia at the time of diagnosis but one of them developed NHL six years later. It is suggested that these monoclonal immunoglobulins may in some cases be associated with malignant lymphoma and that subjects presenting with these immunoglobulins should have a long term follow‐up in order to elucidate the question whether or not lymphoma will develop.