Andreas Killander

Therapeutic effects of low‐dose cytosine arabinoside, alpha‐interferon, 1α‐hydroxyvitamin D3 and retinoic acid in acute leukemia and myelodysplastic syndromes

62 evaluable patients with myelodysplastic syndromes (MDS) or acute leukemia were treated with different combinations of low dose ara‐C, α‐interferon (IFN), 1α‐hydroxyvitamin D3 (vit D3) and retinoic acid. The aim was to study the efficacy and toxicity of each combination. The overall rate was 44%. Of these, 50% responded favorably to the combination of IFN, vit D3 and retinoic acid (IDR), which was comparable to the response rate of 43% for low‐dose ara‐C. The results of the IDR treatment may be explained by additive or synergistic effects between the separate drugs in the combination. Ara‐C and IDR treatment was generally well‐tolerated but interferon gave more side effects than any other drug used in the study. Evaluation of the full combination of ara‐C, IFN, vit D3 and retinoic acid was not possible because of toxicity. Marrow hypoplasia was infrequent (5/27 patients) in cases responding favorably to treatment. Complete remissions were not longer than partial remissions or significant responses.

Evaluation of serum deoxythymidine kinase as a marker in multiple myeloma

Summary. A recently developed deoxythymidine kinase assay utilizing 125I‐iododeoxyuridine as substrate was used in an investigation of sera from 122 untreated patients with multiple myeloma. Most patients had slightly elevated or normal serum deoxythymidine kinase activity (S‐TK), although in some patients values increased by more than forty‐fold were found. S‐TK correlated with the haemoglobin level but did not correlate with sex, age, erythrocyte sedimentation rate, nor with the serum concentrations of creatinine, β2‐microglobulin, Ca or M‐component. The distribution of S‐TK values in IgG, IgA and pure Bence‐Jones myeloma did not differ significantly.

Oxymetholone treatment in myelofibrosis.

ZusammenfassungDie therapeutische Wirksamkeit von Oxymetholon bei fortgeschrittener Osteomyeloflbrose wurde im Rahmen einer prospektiven Studie geprüft. 11 Patienten (4 Frauen, 7 Männer) erhielten 3–5 mg/kg Körpergewicht Oxymetholon. 5 dieser Patienten hatten vorher eine polyzythämische Phase. Alle Patienten hatten bei Beginn des Therapieversuchs eine Anämie, 4 eine Leukopenie und 10 zusätzlich eine Thrombopenie. Eine Hepatosplenomegalie war immer vorhanden. 5 Patienten benötigten vor Behandlung regelmäßig Bluttransfusionen.In 9 von 15 Therapiephasen wurde eine Normalisierung und deutliche Besserung beobachtet. Die Veränderungen des Hämoglobinspiegels und der Plättchenzahl waren signifikant. 4 Patienten verschlechterten sich nach Dosisreduktion oder bei Absetzen von Oxymetholon; 2 davon sprachen erneut an. Bei einem Patienten kehrten die Werte zu den früher bestehenden polyzythämischen Werten zurück. 1 Patient starb durch eine akute Leukämie.Die Ergebnisse der Studie weisen daraufhin, daß Androgene in weit fortgeschrittenen Fällen von Myelofibrose mit transfusionsbedürftiger Anämie oder schwerer Zytopenie von Wert sein könnte.SummaryIn order to study the effect of oxymetholone therapy in advanced myelofibrosis, 11 patients (4 females, 7 males) were given, 3–5 mg per kg body weight, long-term oxymetholone treatment in a prospective multicenter study. Five cases had previously had a diagnosis of polycythemia vera. All patients had anemia initially, 4 leukocytopenia and 10 thrombocytopenia in addition. Hepato-splenomegaly was present in all cases but in varying degree. Five patients required regular blood transfusions before treatment.In 9 of the 15 courses given, there was normalization of the peripheral blood or substantial improvement (better than 3 g hemoglobin/dl or 50×109 platelets/1) after androgens. Significant effects were noted both on hemoglobin values and platelet counts. The need for blood transfusions ceased completely in all 5 cases. When oxymetholone treatment was reduced or interrupted 4 patients relapsed; 2 of them responded to a renewed course. The red cell counts returned to previous polycythemic values in one patient and another died from acute leukemia.The results of this study suggest that androgens might be of value in advanced cases of myelofibrosis with transfusion-requiring anemia or severe thrombocytopenia.

Alternating combination chemotherapy (VMCP/VBAP) is not superior to melphalan/prednisone in the treatment of multiple myeloma patients stage III —A randomized study from MGCS

86 previously untreated patients with multiple myeloma stage III entered a randomized trial comparing combination chemotherapy (VMCP/VBAP) (n = 42) with intermittent oral melphalan and prednisone (MP) treatment (n = 44). The treatment gropus were well comparable with regard to major prognostic factors. There was no statistically significant difference in the response rates, 52% (VMCP/VBAP) vs 61% (MP); in the response duration times, median 19 months vs 22 months, or in the survival times, median 24 months vs 28 months. However, survival of patients older than 65 years was significantly shorter in the VMCP/VBAP group (median 15 months) compared to the MP group (median 23 months) (p = 0.03). No significant difference in non‐hematological or hematological toxicity was noted. The study further supports the notion that MP therapy should be used as primary standard treatment for patients with multiple myeloma.

Treatment of pure red-cell aplasia and aplastic anaemia with ciclosporin: long-term clinical effects.

6 patients with pure red‐cell aplasia were treated with Ciclosporin (Cyclosporine A; CS) alone or combined with prednisolone for a period of 9–46 (median 27) months. Prior to study, 5 cases had refractory disease, steroids were contraindicated in 1, and 4/6 patients, including 2 cases with congenital disease, had a disease duration exceeding 11 years. A complete haematological response was obtained in 5/6 subjects, and a partial response in 1. When the pre‐treatment Hb levels (mean±S.D. = 64±13 g/l, range 41–80) for all 6 PRCA patients were compared with the Hb levels after 6 months of CS therapy (104±17 g/1, 80–125), a significant improvement was registered (p < 0.005). In half of the patients, remission is maintained with CS as single drug in a dose‐dependent manner. We also treated 5 patients with refractory severe aplastic anaemia with CS (1 case) or CS plus prednisolone (4 cases) for 3–27 (median 10) months. Only 1 patient responded. In this case, a complete haematological remission was induced with CS alone, and remission has been maintained for 27 months. Side effects of CS therapy were common but were dose‐dependent and reversible, with the exception of persistent nephrotoxicity in 1 patient with pure red‐cell aplasia. Based on our present results and a survey of the literature, we conclude that CS therapy is effective and indicated in refractory pure red‐cell aplasia. In severe aplastic anaemia resistant to conventional immunosuppression, the response rate is lower, but a small proportion (around 15%) of patients may benefit from CS therapy. Longer treatment periods may, however, be needed to evaluate the role of CS in aplastic anaemia.

Functional capacity of transfused platelets estimated by the Thrombostat 4000/2

Abstract: Post‐transfusion platelet increment is a useful test for the evaluation of transfusion efficacy. It does not, however, give information about the in vivo platelet function. We have evaluated the in vitro bleeding time (IVBT) using the Thrombostat 4000/2 with ADP as activating agent in 60 platelet transfusions given to 17 chemotherapy‐induced severely thrombocytopenic patients. Determinations were performed before and after transfusion of platelet concentrates (PC) prepared from buffy coat. Both fresh and stored platelets resulted in significant reductions of the IVBT already 10 minutes after completed platelet transfusion. In the majority of patients there was a correspondence between IVBT and platelet increment. However, in 30% of the cases there was no improvement of the IVBT despite an increase of the platelet count. Fresh PCs were more effective I than stored. The IVBT seems to represent a clear‐cut improvement in the possibilities for evaluating and monitoring the effect of platelet transfusion.

Biochemical markers in multiple myeloma: a multivariate analysis

Summary. The analysis of individual biochemical and clinical variables in 121 patients with multiple myeloma showed that serum β2‐microglobulin (S‐β2m) had the most significant relation to survival. Other variables such as serum thymidine kinase (S‐TK), serum lactate dehydrogenase (S‐LDH), Screatinine, haemoglobin (Hb), ESR, S‐albumin, age and clinical stage were also significant. No such relationship was found with M‐component, presence of light chains in urine, type of secreted immunoglobulin or S‐calcium. The exclusion of clinical stage in the first multivariate analysis resulted in a model consisting of S‐β2m, age and S‐TK, none of the other variables gave additional information. When in the second multivariate analysis the basic variables involved in staging procedure were excluded and clinical stage included, stage III, but not stage II, was found to give additional information to the model described above.

IDIOPATHIC APLASTIC ANAEMIA IN CHILDREN

The results of treatment of 19 children with idiopathic aplastic anaemia is reported. Initially the patients received testosterone‐prednisone therapy. When a satisfactory haemoglobin level had been reached metandienon was substituted for testosterone and the corticosteroids withheld. 8 patients died without signs of response, 2 patients responded initially but died later. The remaining 9 patients are alive but in only 3 of them was it possible to discontinue all therapy without signs of relapse. The rate of remission varied considerably. One patient required 23 months of combined therapy to achieve a normal haemoglobin level. A moderate hypoplasia of the bone^marrow at the start of therapy was the most favourable prognostic sign in this series. Therefore, it may be concluded that every effort should be made to diagnose the disease before the bone‐marrow changes have progressed to severe hypoplasia.

The serum vitamin B12 levels at various ages.

An investigation of the relation between serum vitamin B12 levels and age and sex of 242 haematologically normal subjects, 0 to 82 years of age was performed.

Treatment of acute nonlymphoblastic leukemia in adults with daunorubicin-DNA complex: A preliminary report

SummaryForty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1+ARA-C on days 1–5; R 2 = courses of daunorubicin on days 1 and 2+ARA-C on days 4–8; R 3 = courses of daunorubicin-DNA complex on days 1–2+ ARA-C on days 4–8.Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.