Correlation of capecitabine-induced skin toxicity with treatment efficacy in patients with metastatic colorectal cancer: results from the German AIO KRK-0104 trial.

BACKGROUND: The AIO KRK-0104 randomised phase II trial investigated the efficacy and safety of two capecitabine-based regimens: combination of capecitabine and irinotecan (CAPIRI) plus cetuximab (CAPIRI-C) and combination of capecitabine with oxaliplatin (CAPOX) plus cetuximab (CAPOX-C) in the first-line treatment of metastatic colorectal cancer (mCRC). Treatment-related skin toxicity (ST) was evaluated separately for capecitabine and cetuximab. The present analysis investigates the correlation of capecitabine-attributed ST (Cape-ST) and parameters of treatment efficacy. METHODS: Patients with mCRC were randomised to cetuximab (400 mg m(-2), day 1, followed by 250 mg m(-2) weekly) plus CAPIRI (irinotecan 200 mg m(-2), day 1; capecitabine 800 mg m(-2), twice daily, days 1-14, every 3 weeks), or cetuximab plus CAPOX (oxaliplatin 130 mg m(-2), day 1; capecitabine 1000 mg m(-2), twice daily, days 1-14, every 3 weeks). RESULTS: Of 185 recruited patients, 149 (CAPIRI-C, n=78; CAPOX-C, n=71) received study treatment beyond the first tumour assessment and were evaluable for efficacy. Capecitabine-attributed ST, predominantly hand-foot syndrome, was observed in 32.2% of patients. Capecitabine-attributed ST grade 1-3 was associated with a significantly higher disease control rate (DCR) (97.9 vs 86.1%, P=0.038) compared with grade 0 toxicity. Moreover, Cape-ST grade 1-3 related to a markedly longer progression-free survival (PFS) (9.9 vs 5.6 months, P<0.001) and overall survival (OS) (32.8 vs 22.4 months, P=0.008). Separate analyses of treatment arms indicated that the effect of Cape-ST on PFS remained significant for both arms, whereas the effect on OS remained apparent as a strong trend. CONCLUSION: This analysis supports the hypothesis that for the evaluated regimens, a correlation exists between Cape-ST and treatment efficacy regarding DCR, PFS, and OS.

Removal of breast cancer cells from bone marrow by in vitro purging with ether lipids and cryopreservation.

Four cell lines from human breast cancer (HTB 19, HTB 133, IZB B, and MCF 7M) were investigated for in vitro growth before and after incubation with the ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) for 4 h and at increasing concentrations (25, 50, 75, and 100 micrograms/ml), as well as with and without cryopreservation. When measured with the human tumor cloning assay in agar or methyl-cellulose the surviving fraction showed an inverse correlation with the concentrations of ET-18-OCH3. After a 4-h exposure with 75 micrograms/ml ET-18-OCH3 at a cell density of 2 x 10(5)/ml the number of colonies of HTB 19 decreased from 75 +/- 10/10(3) cells (100%) to 1 +/- 0/10(3) cells (1%), and after subsequent cryopreservation no remaining colonies were found. In order to simulate the situation in autologous bone marrow transplantation we contaminated normal human bone marrow cells with malignant HTB 19 breast cancer cells at a ratio of 100:1. After incubation with 75 micrograms/ml ET-18-OCH3 for 4 h and subsequent cryopreservation there was a considerable reduction of HTB 19 colonies whereas the majority of normal human hematopoietic progenitors recovered. We conclude that ET-18-OCH3, in combination with cryopreservation, can remove breast cancer cells from bone marrow by up to 1 log and may be useful for purging bone marrow for autologous bone marrow transplantation not only in acute leukemia and non-Hodgkin's lymphoma but also in breast cancer.

An update: 12-year follow-up of patients with hairy cell leukemia following treatment with 2-chlorodeoxyadenosine.

Long-term results of both pretreated and previously untreated patients (pts) with hairy cell leukemia (HCL) using uniformly a single 7-day course of 2-chlorodeoxyadenosine (2-CdA) by continuous infusion are reported. In addition, the probability of obtaining another response with this drug in pts who relapsed after 2-CdA treatment will be addressed. A total of 44 consecutive pts (34 males, 10 females) with a median age of 57 years (range 33-77) at the time of initiation of 2-CdA treatment were analyzed. In all, 11 pts were pretreated with either splenectomy (n=6), interferon alpha (n=9) or deoxycoformycin (dCF) (n=3) or all procedures in sequence. Two pts treated with dCF did not respond to dCF, but only 2-CdA. The median time to the start of 2-CdA treatment of the 11 pretreated pts was 47 months (mo) (10-160). Out of 44, 43 (98%) achieved complete response (CR) (13 pts with residual disease-RD), one pt reached a good partial response with a single cycle of 2-CdA. Out of 44 pts, 13 had no nonhematologic toxicities at all. Toxicities (WHO grade I-IV) were mainly of grade I and II, in one pt grade IV infectious complication. Bone marrow biopsies were performed at the time of recovery of hematopoiesis, thereafter at 2-3 mo intervals, thereafter at 6 mo, and finally annually in 35 pts. The median follow-up is 8.5 years (0.1-12.2). Disease-free survival from the start of 2-CdA treatment is 36% at 12 years (median 8.4 years), 17/44 pts relapsed. Nine of these pts were treated with 2-CdA again, eight achieved a second CR (median 2.5 yrs), one pt did not respond. Eight of our cohort had a second malignancy before receiving 2-CdA. Six pts died in CR due to the second malignancy. The overall survival at 12 years after the start of 2-CdA treatment is 79%. 2-CdA is a safe and effective treatment of HCL inducing complete remissions in the majority of pts with only a single cycle of 2-CdA, and a paucity of toxicities. Responses are durable and long-lasting. Pts who relapsed following treatment with 2-CdA responded to subsequent retreatment with 2-CdA.

Prednimustine, mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) for the treatment of advanced low-grade non-Hodgkin's lymphoma. German Low-Grade Lymphoma Study Group.

The current study was initiated to compare the anti-lymphoma activity and side-effects of prednimustine/mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) in patients with advanced low-grade non-Hodgkin's lymphomas in way of a prospective randomized multicenter trial. Two hundred and forty-six patients with stage III or IV centroblastic-centrocytic (CB-CC (Kiel-classification)) or follicle center lymphoma (FCL (REAL classification)) and centrocytic (CC) or mantle-cell-lymphoma (MCL) were randomized for therapy with either PmM or COP and are fully evaluable for response and toxicity. PmM consisted of prednimustine 100 mg/m2/day on days 1-5 and mitoxantrone 8 mg/m2 /day days 1 and 2, while COP comprised cyclophosphamide 400 mg/m2/day on days 1-5, vincristine 1.4 mg/m2/day on day 1 and prednisone 100 mg/m2/day on days 1-5. Both regimens were repeated for a total of six cycles followed by an additional two courses for consolidation in responding cases and a subsequent second randomization for interferon alpha maintenance vs observation only. Overall response rates were comparable with 83% complete and partial remissions after COP and 84% remissions after PmM. PmM revealed a significantly higher rate of complete remissions (36 vs 18%, P < 0.006), the majority being achieved after four courses. The more rapid and possibly also more effective reduction of the lymphoma cell mass by PmM resulted in a tendency to a longer event-free interval for patients achieving remissions after PmM as compared to COP with estimated median event-free intervals of 31 vs 14 months, respectively (P=0.04). Separate analysis of lymphoma subtypes showed a tendency to a lower rate of complete remission in CC or MCL as compared to CB-CC or FCL (16 vs 30%, P=0.12, NS) while overall response rates were in a similar range (81 vs 85%). In both subtypes, PmM induced a higher rate of complete remission while overall response rates were comparable after PmM or COP. Treatment associated side-effects comprised predominantly myelosuppression and granulocytopenia in particular which was more frequently observed after PmM than COP (43 vs 31 %, P < 0.0001). This difference was clinically irrelevant, however, since serious infectious complications were encountered in less than 3% of cycles after both regimens. COP therapy was associated with a significantly higher incidence and degree of hair loss and complete alopecia (31 vs 2%) as well as of peripheral neurotoxicity (23 vs 2%). These data show that both PmM and COP reveal a high anti-lymphoma activity in patients with advanced stage non-Hodgkin's lymphoma. PmM appears advantageous with a higher rate of complete remissions and a better tolerability with regard to secondary side-effects. A longer follow-up is needed to assess the long-term effects of initial treatment on disease-free and overall survival and the impact on additional maintenance therapy with interferon alpha.

Differential cytotoxicity of an ether lipid on lymphoma and bone marrow cells and its role in purging malignant lymphoid cells from remission bone marrow contaminated with tumor cells.

Four human clonogenic malignant lymphoid cell lines (CEM, Su-DHL-4, Li-A, and Raji) as well as normal human bone marrow stem cell progenitor cells were investigated for clonal in vitro growth before and after incubation with the ether lipid ET-18-OCH3 for various times (1, 4, and 18 h) and at increasing concentrations of the drug (25, 50, 75, and 100 micrograms/ml). The clonal growth of the malignant lymphoid cell lines was inversely correlated with concentrations and times of drug incubation. The antineoplastic effect of ET-18-OCH3 was further amplified by subsequent cryopreservation. In a situation of 4-h exposure to less than or equal to 50 micrograms/ml ET-18-OCH3 and subsequent cryopreservation, in which greater than 50% of the normal human bone marrow progenitor cells survived, 1-3 logs of the malignant lymphoblastoid cells were killed, indicating a potential value of this drug for bone marrow purging in lymphoid malignancy. In order to simulate the situation of autologous bone marrow transplantation (ABMT) in complete remission of the disease, we contaminated normal human bone marrow cells with malignant CEM or Su-DHL-4 lymphoid cells at a ratio of 100:1. Results show that 4 h of incubation with 75 micrograms/ml ET-18-OCH3 and subsequent cryopreservation can eliminate 2-3 logs of clonogenic cells of the malignant lymphoblastoid cell lines under conditions that allow recovery of greater than 50% of the normal human hematopoietic progenitors.

Molecular evidence of bone marrow involvement in advanced case ot Tgammadelta lymphoma with secondary myelofibrosis.

We describe the case of a middle-aged man with long indolent course of generalized Tgammadelta lymphoma. The onset of secondary myelofibrosis made cytological monitoring of the bone marrow infiltrates impossible. As during progression of the disease splenectomy revealed typical histological features of a high-grade hepatosplenic Tgammadelta lymphoma, the low-grade bone infiltrate was considered a secondary lymphoma. The use of the polymerase chain reaction helped to detect a constant and identical monoclonal rearrangement pattern of the T-cell receptor gamma-chain gene in both bone marrow and splenic T-cell infiltrates. The notion of a secondary spread of malignant T-cells to the bone marrow was thereby confirmed despite striking cytological differences between bone marrow and splenic infiltrates. This is the first report of a diagnostic DNA-based molecular approach using fixed decalcified bone marrow. This method may provide a major tool when dealing with myelofibrosis, which normally hampers sampling of cytological specimens.

[Treatment of chemotherapy-induced nausea and vomiting with 5-hydroxytryptamine type 3 receptor antagonists]. / Antiemetische Therapie mit 5-HT(3)-Antagonisten in der onkologischen Praxis.

BACKGROUND AND OBJECTIVE: 5-hydroxytryptamine 3 (5-HT3) receptor antagonists have proved to be highly efficacious in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). However, several questions remain concerning the relative efficacy of various approved anti-emetics, especially with respect to dosage, duration and timing of administration, as well as differences in toxicity profiles. Thus it seemed appropriate to assess the current therapeutic results in routine daily practice, when applying antiemetic therapy according to established guidelines. PATIENTS AND METHODS: Within LINO e.V., a group of medical oncologists in private ambulant practice (LINO: Association of private-practice medical oncologists in Bavaria), a total of 738 cycles of moderately or highly emesis-inducing chemotherapy were randomly assigned to three treatment options: (1)granisetron 1 mg (GRA1). (2) 3 mg (GRA3), and (3) ondansetron 8 mg (OND8), each combined with 8 mg dexamethasone. Incidence and severity of acute (day 1) and delayed CINV (day 2-5) and the subjective assessment of efficacy were documented on questionnaires filled in by the patients. RESULTS: All of the three regimens adequately prevented vomiting in the majority of the patients. However, all measured effects showed an uniform trend towards slightly decreased efficacy with 8 mg of ondansetron. These differences were predominantly detected with respect to delayed CINV on days 2 to 5, especially after chemotherapy with anthracyclin/cyclophosphamide combination therapy. CONCLUSION: Granisetron, at two different dosage regimens, and ondasetron showed adequate reduction in chemotherapy-induced nausea and vomiting, but ondansetron worked slightly less so.

Phase II study of weekly oxaliplatin plus infusional fluorouracil and folinic acid (FUFOX regimen) as first-line treatment in metastatic gastric cancer.

Oxaliplatin plus fluorouracil/folinic acid (5-FU/FA) every 2 weeks has shown promising activity in advanced gastric cancer. This study assessed the efficacy and safety of weekly oxaliplatin plus 5-FU/FA (FUFOX regimen) in the metastatic setting. Patients with previously untreated metastatic gastric cancer received oxaliplatin (50 mg m(-2)) plus FA (500 mg m(-2), 2-h infusion) followed by 5-FU (2000 mg m(-2), 24-h infusion) given on days 1, 8, 15 and 22 of a 5-week cycle. The primary end point of this multicentre phase II study was the response rate according to RECIST criteria. A total of 48 patients were enrolled. Median age was 62 years and all patients had metastatic disease, with a median number of three involved organs. The most common treatment-related grade 3/4 adverse events were diarrhoea (17%), deep vein thrombosis (15%), neutropenia (8%), nausea (6%), febrile neutropenia (4%), fatigue (4%), anaemia (4%), tumour bleeding (4%), emesis (2%), cardiac ischaemia (2%) and pneumonia (2%). Grade 1/2 sensory neuropathy occurred in 67% of patients but there were no episodes of grade 3 neuropathy. Intent-to-treat analysis showed a response rate of 54% (95% CI, 39-69%), including two complete responses. At a median follow-up of 18.1 months (range 11.2-26.2 months), median survival is 11.4 months (95% CI, 8.0-14.9 months) and the median time to progression is 6.5 months (95% CI, 3.9-9.2 months). The weekly FUFOX regimen is well tolerated and shows notable activity as first-line treatment in metastatic gastric cancer.

Bioavailability of bi- and trivalent oral iron preparations. Investigations of iron absorption by postabsorption serum iron concentrations curves.

Since 1977 the bioavailability of 14 bi- and trivalent oral iron preparations has been investigated in five separate orientated clinical studies by using postabsorption serum iron concentration curves. The range of relative bioavailability was 46 to 100% in the first group of preparations, 31 to 47% in the second group and 6 to 29% in the third group. The first group contained mainly bivalent quick release preparations, the second group slow or sustained release preparations and the third mainly trivalent iron preparations. The postabsorption serum iron concentration curves which show a good congruence with exact 59Fe whole body retention tests again confirmed the nearly 50-year-old rule that bivalent iron is up to 16 times better absorbed than trivalent iron. There is no doubt that the oral iron preparations of good bioavailability are able to cure an iron deficiency more rapidly than iron preparations with a low bioavailability. This therefore has a clear influence on the overall expense of iron therapy. Only those preparations from the first group can be recommended for oral iron therapy. The preparations in the second group are less suitable and those in the third group should be excluded from iron therapy in all countries.

[Therapy with blood components (author's transl)]. / Therapie mit Blutkomponenten.

This survey is concerned with the differentiated application of blood and cell concentrates. The indications for administration of blood conserve, fresh blood, erythrocyte and thrombocyte concentrates are carefully delimited. From the point of view of specific therapeutic procedure it is necessary to consider transfusion of conserved blood as an immediate first aid stopgap. For massive transfusions fresh blood, and particularly in special cases warm blood, should be used as soon as possible. In chronic anemias erythrocyte concentrate free from buffy coat is the cornerstone of substitution therapy. In chronic bone marrow insufficiency frequent transfusions lead to alloimmunization and refractivity. In order to have hemostatically active thrombocyte concentrate available, the possibilities of selection of donors and pretesting by means of crossmatching are discussed.

[Comparison of bio-availability, antianaemic efficacy, tolerance and drug costs in oral iron(II) and iron(III) preparations (author's transl)]. / Vergleich von Bioverfügbarkeit, antianämischer Wirksamkeit, Verträglichkeit und Arzneikosten bei oralen Eisen(II)- und Eisen(III)-Präparaten.

In addition to a clinical study which investigated the bio-availability of three oral iron preparations S, L and X by using postabsorption serum iron concentration curves, the same drugs were compared in order to study their antianaemic efficacy, tolerance and drug costs arising during and iron therapy. Moreover, these iron drugs were related to other current clinical reports. Within all three iron preparations a very good correlation was found between bio-availability and haematopoietic efficacy: The very good absorbability of the bivalent quick release stick capsule preparation S (= 100%) corresponded with a very good capacity of haemoglobin regeneration (2,6 +/- 0,4 g Hb/1/day) whereas due to a very low absorbability (10% to 16%) the antianaemic efficacy of both iron(III) preparations L and X had to be rated as moderate to predominantly poor. In normal therapeutic dosis all three iron preparations showed no differences in tolerance. The ratio of side effects was similar to that after ingestion of placebo. In comparing the drug costs during a therapy leading to a real absorption of 1 g of iron the most effective iron(II)sulfate preparation S is 3.6 to 12.6 times cheaper than the compared trivalent preparations L and X. Therefore, there is no justification for the further production or introduction on the market of trivalent iron preparations.

[Investigations of the bioavailability of iron from bi- and trivalent iron salts (author's transl)]. / Untersuchungen zur Bioverfügbarkeit des Eisens aus Eisen(II)- und Eisen(III)-Salzen

In a clinical pilot study, performed as an intraindividual comparison, 3 oral iron preparations, one bivalent iron sulfate (quick release stick capsule preparation) and two trivalent iron citrate complex preparations with different additives, were investigated on 9 healthy young male test persons by the iron absorption test (postabsorption serum iron concentration curves) in order to study the bioavailability of these drugs and their compatibility. Whereas both iron drugs proved equally compatible when administered in therapeutical doses, it was again confirmed that the enteral bioavailability of the ferrous iron sulfate is superior to that of the ferric iron complex preparation. According to these results the medication of ferric iron preparations seems once again to be proved unsuitable, trivalent iron having first to be reduced to bivalent absorbable iron, there however being usually not enough "reducing capacity" in the gastrointestinal tract to do this.

[Clinical course of hairy cell leukemias]. / Beobachtungen zum Verlauf von Hairy-cell-Leukosen.

When analyzing 20 cases of hairy-cell leukosis we can compare a group with a medium survival time (16 months since clinical beginning of the illness) to a group with a long survival time (80 months). Patients (historically older) with short survival times are characterized by a combination of short anamnestic dormancy, younger age, severe symptoms and the applying of a steroid and cytostatic therapy instead of splenectomy. Prevalent causes of death were infections which seemed to increase by cytostasis. Patients with a longer survival time were characterized by a longer survival time were characterized by a longer anamnestic dormancy (up to 15 years), and clinically bland indications that permitted splenectomy. In this group we find interesting cases in which after splenectomy the infiltration of the bone marrow was greatly reduced, being in one case merely 10% after 10 years. These findings ought to be discussed with respect to the aspect of the extremely slow and spleen dependent kinetics of the pathognomy of the cell fractions. As to the origin of the hairy cells and to mark the difference to other lymphomas of the spleen it is necessary to stress the fact that the rate of immunoglobuline did not change in any of the 20 cases observed.

[Hematomorphological differential diagnosis of small cell lymphoma. What is the atypical chronic lymphadenosis?]. / Hämato-morphologische Differentialdiagnose kleinzelliger Lymphome. Was ist die atypische chronische Lymphadenose?

More importance is being attached to haematologic cell morphology, particularly in the field of small-cell non-Hodgkin lymphomas. This shifting of diagnostical validity from the structural substrate to the cellular one can clearly be illustrated by the transition of classification according to Rappoport to that according to Lennert (Kiel-classification). Here minute cytomorphological criteria acquire a new validity by their significance in the microscopic cut preparation and in the electron-microscope as well as by their correlation to cell-immunological parameters. Thus, it is possible to make a differential diagnostics of the extending small-cell lymphomas from the blood picture. It enables an ensured morphological differentiation to be made for typical B-lymphadenosis, prolymphocytic leukaemia, T-cell lymphadenosis, lymphoplasmocytoid immunocytoma, centrocytoma, and hairy cell leukaemia. The relevance of this differentiation can be further identified by a consequent immunologic cell characterization.

Clinical phase I and pharmacokinetic trial of the new titanium complex budotitane.

Budotitane [cis-diethoxybis(1-phenylbutane-1,3-dionato)titanium (IV)] is a novel inorganic metal complex. Preclinical studies in established screening models indicate considerable antitumor activity. We have performed a clinical Phase I and pharmacokinetic trial with budotitane administered as i.v. infusion twice weekly. The starting dose of 100 mg/m2 was derived from a prior single dose Phase I study. Eighteen patients with solid tumors refractory to all other known treatment modalities were entered. 17 patients had received prior chemotherapy. Dose levels ranged from 100 mg/m2 to 230 mg/m2, with a total of 122 budotitane infusions administered. Neither leuko- nor thrombocytopenia were observed. 2/5 pts at 180 mg/m2 and 2/4 pts at 230 mg/m2 developed a 3-fold increase of reticulocytes without signs of hemolysis or bleeding. Nonhematologic toxicity was moderate at doses of < or = 180 mg/m2. Fifteen patients reported loss of taste at the day of infusion. At 230 mg/m2, 2/4 pts developed WHO grade 3 cardiac arrhythmias with polytope premature ventricular beats and nonsustained ventricular tachycardia. A limited pharmacokinetic analysis was performed at dose levels 180 mg/m2 and 230 mg/m2. At 180 mg/m2, Cmax was 2.9 +/- 1.2 microg/ml, t1/2 78.7 +/- 24.4 h, Cltot 25.3 +/- 4.6 ml/min and AUC 203 +/- 71.5 h x microg/ml. At 230 mg/m2, Cmax was 2.2 +/- 0.8 microg/ml, t1/2 59.3 +/- 12.1 h, Cltot 44.9 +/- 23.6 ml/min and AUC was 183 +/- 90.4 h x microg/ml. No objective tumor response was observed. We conclude that the maximum tolerated dose of budotitane administered twice weekly is 230 mg/m2, the dose limiting toxicity is cardiac arrhythmia. Further evaluation of the nature of the cardiac toxicities observed is warranted. Using this schedule, 180 mg/m2 is a safe dose for subsequent clinical studies.

Extramedullary plasmacytoma: tumor occurrence and therapeutic concepts.

BACKGROUND: Extramedullary plasmacytoma (EMP) is a rare entity belonging to the category of non-Hodgkin lymphoma. EMPs make up 4% of all plasma cell tumors and occur mainly in the upper aerodigestive tract (UAD). Seven patients with EMP included in this evaluation were under the authors' care and have been clinically followed since 1990. Because there are no general guidelines for the treatment of patients with EMP, the authors tried to obtain detailed data about the occurrence of this disease and also reviewed the therapies that have been used. To do so, they evaluated all EMP cases published in the medical literature until now and included their own experience. METHODS: Based on the clinical course and follow-up of their own EMP patients, the authors evaluated and reinvestigated all EMP cases cited in MEDLINE, Index Medicus, DIMDI (Deutsches Institut fur medizinische Dokumentation und Information, Cologne, Germany), and the reference lists of the publications found through these sources. RESULTS: In a detailed literature search, more than 400 publications between 1905 and 1997 were found, and these revealed that EMP mainly occurs between the fourth and seventh decades of life. Seven hundred fourteen cases (82.2%) were found in the UAD, and 155 cases (17.8%) were found in other body regions. The following therapeutic strategies were used to treat patients with EMP of the UAD: radiation therapy alone in 44.3%, combined therapy (surgery and radiation) in 26.9%, and surgery alone in 21.9%. The median overall survival or recurrence free survival was longer than 300 months for patients who underwent combined intervention (surgery and radiation). This result was statistically highly significant (P = 0.0027, log rank test) compared with the results for patients who underwent surgical intervention alone (median survival time, 156 months) or radiation therapy alone (median survival time, 144 months). In most cases of non-UAD EMP, surgery was performed (surgery alone, 55.6%; surgery and radiation combined, 19.8%; radiation alone, 11.1%), but there were no statistical differences in survival (P = 0.62). Overall, after treatment for EMP in the UAD, 61.1% of all patients had no recurrence or conversion to systemic involvement (i.e., multiple myeloma, MM); however, 22.0% had recurrence of EMP, and 16.1% had conversion to MM. After treatment for EMP in non-UAD areas, 64.7% of all patients had no recurrence or MM, 21.2% had recurrence, and 14.1% had conversion to MM. CONCLUSIONS: The current investigation provides evidence that surgery alone gives the best results in cases of EMP of the UAD when resectability is good. However, if complete surgical tumor resection is doubtful or impossible and/or if lymph node areas are affected, then combined therapy (surgery and radiation) is recommended. These results, which were obtained from retrospective studies, should be confirmed in randomized trials comparing surgery with combined radiation therapy and surgery.

Long-term outcome of hairy cell leukemia treated with 2-chlorodeoxyadenosine.

The long-term results of both pretreated and previously untreated patients with hairy cell leukemia (HCL) using uniformly a single 7-day course of 2-chlorodeoxyadenosine (2-CdA) by continuous infusion are reported. In addition, the probability of obtaining another response with this drug in patients who relapsed after 2-CdA treatment will be addressed. Forty-two consecutive patients (32 men, 10 women) with a median age of 56 years (range 32-75) at the time of initiation of 2-CdA treatment were analyzed. Ten patients were pretreated with either splenectomy (n=6) or interferon a (n=8) or deoxycoformycin (dCF) (n=3) or with all procedures in sequence. Two patients who did not respond to dCF did respond to 2-CdA. Median time to start of 2-CdA treatment of the ten pretreated patients was 47 months (10-160); 41 of the 42 (98%) achieved CR, and one patient reached a good partial response with a single cycle of 2-CdA. Ten of the 42 patients had no toxicities at all. Toxicities (WHO grades I-IV) were mainly of grades I and II; in one patient with a preexisting brain injury grade III neurotoxicity was seen, and one patient suffered a grade-IV infectious complication. Bone marrow biopsies were performed at the time of recovery of hematopoiesis, thereafter at 2- to 3-month intervals, then at 6 months, and finally annually in all 42 patients. Median follow-up is 32 months (2-72). Disease-free survival from start of 2-CdA treatment is 75% at 6 years; 6/42 patients relapsed. Three of these patients were treated with 2-CdA again. All three patients reached another CR (+1, +2, +13). Four of the 42 patients had a second malignancy (carcinomas of the bladder, breast, cervix, prostate gland) before receiving 2-CdA. One patient died in CR due to the second malignancy. 2-CdA is a safe and effective treatment of HCL, inducing complete remissions in the majority of patients with only a single cycle of 2-CdA and a paucity of toxicities. Responses are durable and long lasting. Patients relapsing following a treatment with 2-CdA seem to respond to this drug again.

[Clinical observations to characterize splenomegalic immunocytomas (author's transl)]. / Klinische Beobachtungen zur Charakterisierung des splenomegalen Immunozytoms.

In ten patients with predominant splenomegaly the clinical development and progress of disease following the course of some years are described. The hematological values showed a moderate relative lymphocytosis with a slight but inconstant increase in white blood cell counts. A more or less small number of a morphologically distinctive population of plasmacytoid lymphocytes was an important diagnostic criterion and a decrease of at least one class of immunoglobulins could be shown. Only one patient presented a paraproteinemia (IgM). In the serum of six patients atypical unspecific antibodies were found. The histologic and cytologic feature of the spleens which were removed therapeutically was characterized by a mixed infiltration of lymphocytes and plasmocytoid or plasmacellular elements. By this pattern it was possible to classify these cases as lymphoplasmocytoid (resp. lymphoplasmocytic) immunocytomas according to the new Kiel-lymphoma-classification. From the clinical point of view they represented a subunit with markedly prevalent splenic proliferation. Liver and/or bone-marrow however showed in all cases primarily circumscribed infiltrations of pathognomonic cells or did develop them during the course of disease, even after splenectomy. According to the presented observations this disease is to be placed between chronic lymphocytic leukemia and M. Waldenström not only by pathological but also by clinical criteria.