50 patients with hairy cell leukaemia (HCL) were treated with recombinant interferon (IFN) alpha‐2b 2.0 × 10 6 IU/m 2 subcutaneously three times weekly to evaluate the efficacy of low‐dose IFN therapy in inducing and maintaining remission of the disease. At the time of this report 48 patients, of whom 22 were splenectomized, had been treated for at least 3 months and were considered evaluable for response. The median observation time on IFN‐alpha‐2b was 11 months (range 3 to 20). 4 cases with atypical disease (spongy lymphoid myelofibrosis) were also included. All patients responded to IFN. After 3 months 11/48 patients (23%) had achieved a partial remission (PR) with normalization of peripheral blood values. After 6 months 27/43 patients (63%) had achieved a favourable response; complete remission (CR) was recorded in 4 and PR in 23 patients. The proportion of patients with favourable responses (CR + PR) increased with the duration of therapy and after 12 months of therapy 23/28 (82 %) patients showed CR or PR, 9 patients (32 %) being in CR. Splenectomized patients disclosed a trend towards a more rapid response. It is concluded that IFN‐alpha‐2b is a highly effective first‐line therapy for HCL
Abstract: l ‐Asparaginase treatment during induction therapy in acute lymphoblastic leukaemia (ALL) is known to be frequently complicated by thromboembolic events. It was recently suggested that l ‐asparaginase derived from Erwinia chrysanthemi alters the coagulation system less severely than does Escherichia coli asparaginase. In a series of 11 adult patients with ALL, we investigated some parameters of the coagulation system during treatment with Erwinia asparaginase. The doses employed were rather high; all patients below the age of 60 years received 15000 U/m 2 daily over 14 days. In accordance with what is known from treatment with E. coli asparaginase, we observed significant lowering of antithrombin as well as of fibrinogen. However, as to fibrinogen indeed a significant decrease had occurred prior to the institution of Erwinia asparaginase treatment. The most striking observation in the present study was that the levels of prothrombin complex, reflecting the function of K‐vitamin dependent coagulation factors II, VII and X, remained within normal ranges during treatment. This indicates that these coagulation factors were not affected by Erwinia asparaginase, an observation at variance with several reports where E. coli asparaginase was investigated. This latter observation was the only finding which could lend support to the view that Erwinia asparaginase affects the coagulation system less than E. coli asparaginase. Finally, one of our patients developed a sinus thrombosis, a severe thrombotic complication.
Patients with relapsed aggressive lymphoma after high dose chemotherapy have a very poor prognosis and long-term survival is rare. Most patients are not eligible for allogeneic stem cell transplantation in this setting and treatment, therefore, becomes palliative. A few studies have shown that trofosfamide, an oral alkylating agent, may be effective as palliative treatment in non-Hodgkin's lymphoma. Trofosfamide therapy is considered rather non-toxic with an overall response rate from 50 to 80%. Most responses are, however, partial and their duration is short. We report a patient with a very aggressive ALK+ anaplastic large cell lymphoma (ALCL), relapsing shortly after high dose chemotherapy. Unrelated allogeneic transplantation was not possible. After several radio/chemotherapy regimens trofosfamide was started as palliative treatment. This therapy resulted in a complete remission, still ongoing, 27 months after termination of intravenous cytotoxic therapy and 16 months after withdrawal of trofosfamide. Thus, in this particular case, trofosfamide turned out to be an unexpectedly effective salvage therapy for an otherwise very aggressive relapsing ALCL.
Mucosal lesions were produced in feline small intestine by evoking a simulated intestinal shock (local hypotension at 30 mm Hg and stimulation of regional sympathetic vasoconstrictor nerves at 6 Hz for 2 h). The degree of mucosal damage was correlated to the level of intestinal blood flow. Microscopically characteristic lesions developed regularly in the small intestinal mucosa when intestinal blood flow was reduced below 12 ml/min × 100 g during the regional shock. The mucosal damage was graded histologically. No difference was found between untreated controls and cats in which the intestinal lumen was perfused with nitrogenated saline. Perfusion with oxygenated saline and i.v. injections of methylprednisolone on the other hand, prevented almost completely the development of the lesions. Albumin, activated charcoal and aprotinin instilled into the intestinal lumen reduced to some extent the mucosal damage. The obtained data support the view that hypoxia is the key factor in the pathogenesis of the mucosal lesions. However, epithelial and intraluminal enzymes are probably important contributing factors.
Interferon-alpha-2b (IFN) was given to a series of 50 patients with hairy cell leukemia (HCL). The IFN dose for both induction and maintenance was 2.0 × 106 IU/m2 s.c. three times weekly. At 24 months 38 patients remained in the study. The proportion of complete responders (CR) increased during the follow-up, and had at 24 months reached 58%, while 28% at the same time had a partial (PR) and 14% a minor response (MR). During the two years of continuous IFN treatment none of the 38 patients showed any signs of relapse. The response rate was similar between splenectomized (n = 15) and non-splenectomized (n = 23) patients, but the rise in platelets was much steeper and reached a significantly higher plateau in patients, who previously had undergone splenectomy. The IFN therapy was generally well tolerated, but when evaluated at 24 months at least some (mostly mild) toxicity was noted in 76% of the patients. None of the patients developed neutralizing antibodies to IFN.
The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.
Iron absorption has been studied in patients with dermatitis herpetiformis (DH). Four patients out of 20 had iron deficiency, defined as absence of or only traces of haemosiderin in bone marrow smears. These four had adequate absorption of ferrous iron. The iron deficiency in at least 3 of them was ascribed to increased iron loss. The results indicate that, although having a mild to moderate malabsorption syndrome, DH patients can be expected to exhibit adequate absorption of orally administered iron. Explanations of a negative iron balance other than defective absorption should therefore be sought.
Hairy cell leukemia (HCL) has been associated with several disease states. In this study, a possible association is reported between HCL and renal cell carcinoma (RCC) and colorectal carcinoma (CRC).A retrospective study of the case records of 50 patients with HCL in a study of alpha-interferon (alpha-IFN) treatment of HCL.Three of 50 patients with HCL studied had RCC, and 2 of these also had CRC. In addition, two other patients had CRC. The other malignant lesions developed either before or after the diagnosis of HCL. In all patients, the HCL responded to alpha-interferon (alpha-IFN), but in four patients, the second lesion was diagnosed during IFN treatment.These findings could indicate that IFN does not correct a possible common basic etiologic defect and shows that even early CRC and RCC do not respond to the IFN doses administered. These findings should be considered in future trials of IFN treatment of these diseases. The authors also recommend a reevaluation of the frequency of second malignant lesions in HCL; this may be important particularly with the increased survival in patients with HCL who receive alpha-IFN treatment.
A 27-year-old woman with acute lymphocytic leukemia developed red painful skin lesions, asymmetrically distributed over the face and extremities. They gradually increased in size and number, and in the center of each lesion blisters appeared followed by central necrosis with surrounding erythema. In several lesions the central necrosis was covered with a white powder shown to be fungal mycelium. Cultures from skin lesions and blood showed a Fusarium species. The skin lesions are helpful in recognizing this deep fungal infection in an immunocompromised host.
