Morphologic diagnosis of leukaemic B-lymphoproliferative disorders and the role of cyclin D1 expression.

PURPOSE: This study analysed the morphologic differences between leukaemic mantle cell lymphoma, follicular lymphoma, nodal marginal zone lymphoma, and diffuse large B-cell lymphoma in peripheral blood. Additionally, we investigated the role of cyclin D1 expression in B-lymphoproliferative disorders. METHODS: The morphologic analysis of the leukaemic cells was performed on cytocentrifuge preparations after separation of mononuclear cells from peripheral blood using a Ficoll-Hypaque density gradient. Cyclin D1 protein expression was studied with the catalyzed signal amplification system. The expression of other markers (CD5, CD23, light chain immunoglobulins) was analysed by the APAAP method. RESULTS: We describe in detail the morphology of the lymphoma cells in eight patients with mantle cell lymphoma, six patients with follicular lymphoma, 11 patients with nodal marginal zone lymphoma, and seven patients with diffuse large B-cell lymphoma. The morphological distinction between these lymphoma cells is a challenge for the haematologist. The investigation of cytocentrifuge preparations of mononuclear cells allows the detection of lymphoma cells also in cases with nondiagnostic white cell differential. Additionally, the immunotype (light chain restriction, CD5, CD23, and cyclin D1) of 108 patients with leukaemic B-lymphoproliferative disorders was studied. Diffuse nuclear expression of cyclin D1 protein (>20%) was specific for mantle cell lymphoma. However, only 6/8 patients showed cyclin-D1 positivity. CONCLUSIONS: The morphologic analysis of lymphoma cells in cytocentrifuge preparations of mononuclear leukocytes in combination with immunocytochemical investigation allows the detection of mantle cells, centrocytes of follicular lymphoma, marginal zone cells, and cells of the diffuse large B-cell lymphoma in peripheral blood. The positivity of cyclin D1 protein improves the differentiation of mantle cells from other lymphoma cells.

Bioequivalence investigation of high-dose etoposide and etoposide phosphate in lymphoma patients.

PURPOSE: To compare etoposide pharmacokinetics following administration of high-dose etoposide and etoposide phosphate, a water-soluble prodrug of etoposide. Bioequivalence was assessed using a two-treatment randomized crossover design. METHODS: Ten patients with high-risk or relapsed lymphoma were treated with a sequential high-dose chemotherapy. They were randomized to receive either 3 x 400 mg/m2 etoposide or an equimolar amount of etoposide phosphate (as 1-h infusions on three consecutive days) in the first course and the alternative drug in the second course. Serial plasma and ultrafiltered plasma samples were collected and analysed for etoposide by a reversed-phase HPLC method with UV and electrochemical detection. Pharmacokinetic parameters were estimated using a two-compartment model. Bioequivalence was assessed calculating the 90% confidence intervals (CI) for the ratios of the geometric means of AUC(0-infinity) and additionally of Cmax of etoposide derived from etoposide phosphate relative to etoposide in plasma and ultrafiltered plasma as point estimates (level of significance alpha < 0.05). RESULTS: Pharmacokinetic parameters of etoposide were comparable in both treatment arms except that terminal half-life was significantly shorter and apparent Vss in ultrafiltered plasma was significantly larger following administration of the prodrug. The point estimates for AUC(0-infinity) of etoposide derived from etoposide phosphate relative to etoposide were 102.9% and 88.4% for plasma and ultrafiltered plasma, respectively. The 90% CIs were in the range from 80% to 125% where bioequivalence can be assumed. The point estimates of Cmax on day 3 of chemotherapy were 96.5% and 81.7% in plasma and ultrafiltrate with the 90% CI in ultrafiltered plasma being out of the range from 80% to 125%. CONCLUSION: With respect to total drug exposure, represented by AUC(0-infinity), high-dose etoposide phosphate is bioequivalent to high-dose etoposide.

Inverse relationship between patient peripheral blood CD34+ cell counts and collection efficiency for CD34+ cells in two automated leukapheresis systems.

BACKGROUND: The purpose of this study was to analyze the CD34 cell collection efficiency (CE) of automated leukapheresis protocols of two blood cell separators (Spectra, COBE [AutoPBSC protocol] and AS104, Fresenius [PBSC-Lym, protocol]) for peripheral blood progenitor cell (PBPC) harvest in patients with malignant diseases. STUDY DESIGN AND METHODS: PBPCs were collected by the Spectra AutoPBSC protocol in 95 patients (123 collections) and the AS104 PBSC-Lym protocol in 87 patients (115 harvests). Patients underwent a median of one (range, 1-4) conventional-volume apheresis procedure of 10.8 L (9.0-13.9) to obtain a target cell dose of > or =2.5 x 10(6) CD34+ cells per kg. RESULTS: The median overall CD34 CE was significantly better on the AS104 than on the Spectra: 55.8 percent versus 42.4 percent (p = 0.000). This was also true below (59.2% vs. 50.1%; p = 0.022) and above (51.2% vs. 41.3%; p = 0.001) the preleukapheresis threshold of 40 CD34+ cells per microL needed to collect a single-apheresis autograft. However, at > or =40 circulating CD34+ cells per microL, both cell separators achieved the target of > or =2.5 x 10(6) CD34+ cells per kg. The CD34 CE dropped significantly, from 59.2 percent at <40 cells per microL to 51.2 percent at > or =40 cells per microL on the AS104 (p = 0.017) and from 50.1 percent to 41.3 percent on the Spectra (p = 0.033). CONCLUSION: Whereas the CD34 CE was significantly different with the AS104 and the Spectra, the CD34 CE of both machines correlated inversely with peripheral blood CD34+ cell counts, showing a significant decline with increasing numbers of circulating CD34+ cells. Nevertheless, at > or 40 preapheresis CD34+ cells per microL, sufficient hematopoietic autografts of > or =2.5 x 10(6) CD34+ cells per kg were harvested by a single conventional-volume (11 L) leukapheresis on both cell separators.

ICE--an efficient drug combination for stem cell mobilization and high-dose treatment of malignant lymphoma.

Between 1989 and 1999 we studied the ICE regimen in sequential trials in 290 patients with malignant lymphoma and germ-cell tumours. For patients with relapsed or refractory lymphoma we could demonstrate a comparable efficacy of ICE to other high-dose chemotherapy (HDCT) regimens but with a toxicity profile in favour of ICE. From a retrospective comparative analysis of ICE as HDCT regimen in patients with malignant lymphoma and germ-cell tumours we conclude that the characteristic toxicity profile of ICE varies depending on prior drug exposure of individual patients. Further dose intensification of ICE may be achieved with acceptable toxicity by adding further drugs (e.g. anthracyclines) or by treatment with sequential cycles of ICE (Tandem-HDCT). More convenient drug formulations (e.g. etoposide phosphate) might further improve the therapeutic index of ICE.

Salvage treatment with paclitaxel, ifosfamide, and cisplatin plus high-dose carboplatin, etoposide, and thiotepa followed by autologous stem-cell rescue in patients with relapsed or refractory germ cell cancer.

PURPOSE: To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors. PATIENTS AND METHODS: Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m(2), ifosfamide 5 x 1.2 g/m(2), and cisplatin 5 x 20 mg/m(2) (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m(2) x 3, etoposide 600 mg/m(2) x 4, and thiotepa 150 to 250 mg/m(2) x 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m(2) and ifosfamide 5 g/m(2) (TI) was given immediately before TIP to improve stem-cell mobilization. RESULTS: Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects. CONCLUSION: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.

Body experience and mental representation of body image in patients with haematological malignancies and cancer as assessed with the Body Grid.

The domain of body image plays a central role in the quality of life of patients with haematological malignancies and metastasized cancer, since the disease itself as well as the enrolled therapies interfere with psychological and bodily well-being. We approached this highly subjective field by using the repertory grid technique and hypothesized that patients would display a restricted body image, focusing on functional aspects of the body. In all, 55 in-patients (27 men, 28 women, M age = 45.7 yrs, N = 46 with haematological malignancies, N = 9 with metastasized cancer), at the time of initial diagnosis, were included in the study and assessed with the Body Grid, an instrument specifically designed by us for the exploration of body image. The data were analysed by principal component analysis (PCA) and construct categorization. Further, 42 chronic tinnitus sufferers (20 male, 22 female, M age = 46.5 yrs) served as a comparison group. Based on the constructs elicited, six construct categories were formulated in the sense of a first attempt of a hierarchical model (emotion, control, activity, strength, function, appearance). The central constructs (373 construct pairs) were assigned to these categories by three inter-raters. The categories appeared in the following order of frequency: function (27.1%), emotion (20.4%), strength (20.1%), activity (15%), control (10.2%) and appearance (7.2%). PCA indicated that the patients mainly demonstrated a restricted view of their body. In the tinnitus group, the most frequent category proved to be activity (21.3%), closely followed by function (21.1%) and control (20.9%). The body image was also restricted (PCA). The restriction of body image, together with the specific construct choice, seen in the haematology and cancer patients reflects the existential threat of the disease and may serve as a coping strategy. The high percentage of emotional constructs may mirror the patients' need for further support. The distinct distribution of construct categories in the two different patient samples supports the applicability of the proposed preliminary model.

Automated collection of peripheral blood stem cells with the COBE spectra for autotransplantation.

BACKGROUND: A convenient, effective and safe peripheral blood stem cell (PBSC) apheresis procedure is desirable to cope with the increasing requirements for PBSC collections. We performed PBSC harvesting with the novel COBE Spectra AutoPBSC(TM) system using the default software configuration recommended by the manufacturer. We analyzed collection parameters and clinical efficiency of harvested autografts following high-dose chemotherapy (HDCT). PATIENTS AND METHODS: Eighty-one patients underwent 102 harvests after standard chemotherapy plus filgrastim (5-10 microg/kg/day) to obtain a target of >/=2.5 x 10(6) CD34+ cells/kg for autologous blood stem cell transplantation. Conventional-volume leukaphereses (median: 11 liters) were performed using the manufacturer's standard software default regarding inlet flow, harvest/chase volume (3/7 ml) and number of collection cycles. The ratio of ACD-A to whole blood was initially set at 1:12 (56 collections), later at 1:10 (46 aphereses). RESULTS: With respect to preapheresis counts of 93 (9-876) CD34+ cells/microl, 69 patients (85.2%) achieved >/=2.5 x 10(6) CD34+ cells/kg by the first apheresis. PBSC products contained medians of 5.0 x 10(6) (0.7-77.3) CD34+ cells/kg and 13.8 x 10(4) (2.3-105.0) CFU-GM/kg. A preapheresis count of >/=40 CD34+ cells/microl predicted a single-apheresis yield of >/=2.5 x 10(6) CD34+ cells/kg. Apheresis products showed a high mononuclear cell (MNC) purity of >/=89%. The median overall collection efficiency of CD34+ cells (CD34-CE) was 42.6% (12.2-87.4). The CD34-CE decreased significantly with increasing numbers of circulating CD34+ cells: 52.5% at CD34+ cells <40/microl versus 41.0% at CD34+ cells >/=40/microl (p 0.5 x 10(3)/microl, 10 (8-13) days for WBC >1.0 x 10(3)/microl and 11 (8-17) days for platelets >20 x 10(3)/microl. CONCLUSIONS: As a result of efficient PBSC mobilization, a single conventional-volume leukapheresis with the COBE Spectra AutoPBSC system resulted in hematopoietic autografts with >/=2.5 x 10(6) CD34+ cells/kg in 85% of patients. Following the standard PBSC apheresis recommendations of the manufacturer, the AutoPBSC system assures PBSC products with a high MNC purity and a moderate CD34-CE that declines significantly at increasing levels of circulating CD34+ cells. Leukaphereses performed at an ACD-A to whole blood ratio of 1:10 should run without coagulation problems.

Diagnosis of toxoplasmosis in bone marrow transplant recipients: comparison of PCR-based results and immunohistochemistry.

Toxoplasmosis in bone marrow transplant recipients is a rare but serious complication and if untreated, almost uniformly fatal. The diagnosis, however, remains difficult. We therefore compared serial determination of antibody titers specific for T. gondii before and after transplantation, serial PCR for T. gondii DNA in serum, PCR and nested PCR for T. gondii DNA in various tissues, conventional histology and immunohistochemistry for detection of parasites in three patients with autopsy-confirmed toxoplasmosis after bone marrow transplantation. Immunohistochemistry demonstrated the presence of parasites in 13 out of 20 organs investigated (65%), whereas PCR detected T. gondii-specific DNA in 15 out of 20 organs (75%). Immunohistochemistry revealed concordant results to PCR data in 60% of the specimens. With the use of a nested PCR protocol, eight out of nine samples (89%) were positive for T. gondii-specific DNA. The combination of both methods detected the presence of parasites in 90% of the specimens. Serial PCR in serum did not yield positive results. Neither PCR nor immunohistochemistry was able to detect parasites in all organs investigated, but both methods together improved sensitivity to 90% and consequently, should be used jointly to maximize diagnostic precision. Bone Marrow Transplantation (2000) 25, 1257-1262.

Successful autologous bone marrow rescue in patients who failed peripheral blood stem cell mobilization.

We assessed autologous bone marrow (BM) harvest and hematologic recovery after high-dose chemotherapy (HDCT) in patients who failed to achieve peripheral blood stem cell (PBSC) mobilization. One hundred and ninety-three patients with germ cell tumor, malignant lymphoma, sarcoma or medulloblastoma were scheduled for HDCT. In 123 patients, PBSC were mobilized by disease-specific chemotherapy plus granulocyte colony-stimulating factor (G-CSF). In 110/ 123 patients (89%) with circulating CD34+ cell counts 2 > or = 10/microl, sufficient hematopoietic autografts were collected (group A). In 13/123 patients (11%) with peripheral CD34 + cell counts < 10/microl, PBSC harvesting was not performed (group B). These latter patients were classified as "poor mobilizers" and underwent second-line BM harvest at a median of 46 (range 10-99) days after mobilization failure. Seventy patients with first-line BM harvest (group C) acted as historical controls. Ten patients from group B proceeded to HDCT and nine were evaluable for hematopoietic reconstitution. Recovery to neutrophils >0.5 x 10(9)/l was comparable with group C patients: 16 (range 9-34) days vs 13 (range 8-98) days. However, platelet (PLT) reconstitution >20 x 10(9)/l was significantly slower, with a median of 35 (range 13-50) days as compared with 19 (range 9-148) days (P = 0.0106) for control patients. Supportive care requirements, febrile days and length of hospital stay were not significantly different between the two groups of patients. We conclude that patients who fail to mobilize PBSC should be evaluated for second-line BM harvest. This approach may preserve the therapeutic option of HDCT for these patients.

Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSF-mobilized peripheral blood stem cell preparation.

Donor lymphocyte infusions (DLI) are an effective treatment of leukemia relapse after allogeneic bone marrow transplantation. Undesired side-effects are the development of graft-versus-host disease (GVHD) and the occurrence of pancytopenia in some patients. In a pilot study, we investigated if unmanipulated G-CSF-mobilized peripheral blood stem cells which naturally contain large numbers of T lymphocytes (D-PBSC/LI) would be equally effective or even superior than DLI in generating a graft-versus-leukemia reaction (GVL) but could mitigate or prevent the development of pancytopenia. We treated 12 patients with CML chronic phase (n = 5), CML blast crisis (n = 2), AML (n = 2), ALL (n = 1), CLL (n = 1) and multiple myeloma (n = 1). In five patients with acute leukemia or CML blast crisis D-PBSC/LI followed intensive chemotherapy (group A), in seven patients D-PBSC/LI were given without any prior chemotherapy (group B). In group A two patients were evaluable for hematologic toxicity. Leukopenia <1000/microl lasted for 10 and 19 days, and thrombocytopenia <20,000/microl for 11 and 13 days, respectively. In group B leukopenia <1000/microl and thrombocytopenia <20,000/microl was observed in only one patient. Moderate cytopenia developed in four of five evaluable patients. A complete remission could be achieved in all seven patients with CML who all developed acute and/or chronic GVHD. None of the remaining five patients achieved a complete remission despite acute and/or chronic GVHD in two of them. Four patients died from disease progression, one patient from a secondary lymphoma, and one patient as a result of uncontrolled GVHD. In conclusion, D-PBSC/LI is effective in inducing GVL reaction but it does not prevent pancytopenia in each case. It remains unclear if it mitigates the incidence and severity of pancytopenia.

High-dose chemotherapy in germ cell tumours: a large single centre experience.

High-dose chemotherapy (HDCT) has evolved as a strategy to improve the treatment outcome in patients with relapsed and/or refractory germ cell tumours. Between August 1989 and September 1995, 150 consecutive patients with relapsed and/or refractory germ cell tumours were treated with conventional-dose salvage chemotherapy followed by one cycle of HDCT with carboplatin 1500-2000 mg/m2, etoposide 1200-2400 mg/m2 and ifosfamide 0-10 g/m2 and were retrospectively analysed. With a median follow-up time of 55 months (range 21-88 months) 51/150 (34%) patients are alive and disease free. The projected event-free and overall survival are 29% (confidence interval 22-37%) and 39% (confidence interval 31-47%) respectively. The relevance of prognostic variables for long-term survival after HDCT were prospectively confirmed. Persisting toxicities occurred in approximately one third of the long-term survivors. Treatment intensification with HDCT resulted in a significant proportion of the long-term survivors in patients with relapsed and/or refractory germ cell tumours. Trials to prospectively evaluate HDCT as an early intervention in these patients seem justified.

Nephrotoxicity after high-dose carboplatin, etoposide and ifosfamide in germ-cell tumors: incidence and implications for hematologic recovery and clinical outcome.

High-dose carboplatin, etoposide and ifosfamide (CEI) is an active chemotherapy regimen (HDCT) in solid tumors and lymphomas. In patients with previous exposure to cisplatin, its nephrotoxicity is dose-limiting. To determine the implications of nephrotoxicity on hematological recovery and clinical outcome, we analyzed 150 consecutive patients with germ cell tumors treated between August 1989 and September 1995 with carboplatin 1500-2000 mg/m2, etoposide 1200-2400 mg/m2, and ifosfamide 0-10 g/m2 followed by either BM or PBPC rescue. Five patients died (3%), three in the context of severe renal toxicity and early multiorgan failure. Overall, acute nephrotoxicity occurred in 43/150 (29%) patients, particularly at doses of carboplatin >1500 mg/m2. Hemodialysis was required in 12/150 (8%) patients, but could be discontinued until discharge in all except two survivors. Nephrotoxicity did not delay hematologic recovery when adjusted for the use of PBPC and hematopoietic growth factors by multivariate analysis, but resulted in higher transfusion requirements, more overall toxicities and a longer hospital stay. There were no differences in the response rates or survival in patients with or without nephrotoxicity. Acute nephrotoxicity is a frequent and clinically relevant complication of CEI in germ cell tumors. The acute side-effects from CEI are reversible in the majority of patients.

Chronic lymphatic leukemias of T and NK cell type.

T cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL) and large granular lymphocyte leukemia of T or NK cell type (T-LGL or NK-LGL leukemia) are chronic lymphoproliferative diseases derived from post-thymic immunocompetent lymphoid cells. T-PLL is morphologically characterized by a prominent central nucleolus in a medium-sized cell expressing a mature T cell immunophenotype. Clonal genetic changes involving chromosome 14 and T cell receptor gene rearrangements are characteristics of these diseases. They are usually progressive and there is no efficient treatment available. The classification of some cases presenting with a morphological picture similar to B-CLL, but with immunophenotypic and clinical features resembling T-PLL, as T-CLL is still controversial. The phenotypic profiles and the establishment of clonality are the hallmarks of defining T-LGL leukemia and NK-LGL leukemia. The CD3+/CD57+/CD56- immunophenotype and the clonal rearrangement of the T cell receptor genes characterize T-LGL leukemia, which presents clinically with a rather indolent course of disease, complicated by frequent infections secondary to neutropenia. NK-LGL leukemia cells express CD3-/CD56+/CD57-, but in most cases clonality cannot easily be established. Clinically the patient may either present with constitutional symptoms and suffer a short and aggressive course of disease or may have a more chronic disease similar to T-LGL leukemia. Therefore, it may be reasonable to subdivide NK-LGL proliferation into the more aggressive 'NK-LGL leukemia/lymphoma' and 'chronic NK cell lymphocytosis'.

Long-term survival of patients with recurrent or refractory germ cell tumors after high dose chemotherapy.

BACKGROUND: The optimal treatment of patients with recurrent or refractory germ cell tumors is still a debated topic. High dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) might be promising for intensification of first or subsequent salvage treatment. However, the long-term results of this approach remain largely unknown. METHODS: Between August 1989 and September 1992, 74 patients with recurrent and/or refractory germ cell tumors were treated in a Phase I/II trial with HDCT consisting of carboplatin (1500-2000 mg/m2), etoposide (1200-2400 mg/m2), and ifosfamide (0-10 g/m2). In September 1995 all patients were reevaluated to determine overall response, late toxicities, and survival. RESULTS: Two patients died from treatment-related toxicity shortly after HDCT, and 47 had recurrence or progression of disease after a median of 3 months (range, 1-44 months). Of these latter patients, three were living continuously disease free at the conclusion of this study after a second HDCT regimen, salvage surgery, or chronic oral etoposide treatment. The results were an overall survival of 38% (95% confidence interval, 27-50%) and a failure free survival of 31% (95% confidence interval, 21-43%) at 5 years. There were no long-term survivors among patients whose disease progressed while they were receiving conventional doses of cisplatin before HDCT. Late toxicities consisted mainly or renal impairment (in 21% of patients), paresthesias (in 29%), and ototoxicity (in 18%). CONCLUSIONS: HDCT can be curative for patients with germ cell tumors who do not become disease free after conventional dose chemotherapy but respond to this treatment.

Peripheral blood progenitor cell collection during hematopoietic recovery following autologous blood progenitor cell transplantation.

BACKGROUND AND OBJECTIVES: Peripheral blood progenitor cells (PBPC) are increasingly used for autologous transplantation after high-dose radio/chemotherapy in patients suffering from cancer. PBPC are usually collected after mobilization with conventional-dose chemotherapy plus growth factor. However, it is conceivable to perform leukapheresis for the second autograft during recovery of hematopoiesis after the first course of HDCT/ABPCT. MATERIALS AND METHODS: We treated two patients this way. In the first, with germ cell cancer, six 12-liter leukaphereses yielded 1.8 x 10(6) CD34+ cells/kg after mobilization with cis-platinum, etoposide and ifosfamide (PEI) plus granulocyte colony-stimulating factor (G-CSF). The second patient, with relapsed Hodgkin's disease, underwent PBPC collection after treatment with dexamethasone, carmustine, etoposide, cytarabine and melphalan (DexaBEAM) plus G-CSF. Due to excellent mobilization, 8.5 x 10(6) CD34+ cells/kg were collected by one 12-liter leukapheresis. Both patients then underwent PBPC collection during hematopoietic recovery following HDCT and ABPCT. RESULTS: In patient 1, following HDCT and ABPCT, three 12-liter aphereses resulted in 0.7 x 10(6) CD34+ cells/kg. In patient 2, also after HDCT and ABPCT, a second autograft with 3.2 x 10(6) CD34+ cells/kg was harvested by a single 10-liter apheresis. No adverse effects were seen in either patient during apheresis following ABPCT. To our knowledge this is the first report dealing with PBCT collection during hematopoietic recovery following HDCT and ABPCT. CONCLUSIONS: (1) PBPC harvesting is feasible and well tolerated in this setting. (2) In appropriate patients with efficient PBPC mobilization after conventional-dose chemotherapy, a further PBPC autograft can be collected during recovery of hematopoiesis after ABPCT, serving as a rescue for a second course of HDCT.

High-dose chemotherapy with carboplatin, etoposide and ifosfamide followed by autologous stem cell rescue in patients with relapsed or refractory malignant lymphomas: a phase I/II study.

Patients with relapsed or refractory non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) with recurrences after an anthracyclin-containing regimen only have a chance of cure of below 10% with conventional chemotherapy. In order to improve their prognosis, we started a phase I/II trial using high-dose therapy comprising carboplatin, together with etoposide and ifosfamide (CEI), followed by autologous stem cell rescue (ASCR) as consolidation after salvage treatment. Since September 1990, 40 patients with intensively pretreated advanced NHL (n = 24) or HD (n = 16) received one cycle of high-dose therapy (HDT) consisting of carboplatin 1500 mg/m2, ifosfamide 10 g/m2 and etoposide in escalating doses from 1200 mg/m2 to 2400 mg/m2 followed by ASCR. Thirty-nine patients were assessable for toxicity and response. The following doses appeared to be safe: carboplatin 1500 mg/m2, etoposide 2400 mg/m2 and ifosfamide 10 g/m2. All patients developed grade 3 nausea and grade 3 or 4 mucositis. Granulocytopenic fever occurred in 100% with grade 4 infections in 15%. Mild transient kidney toxicity was noted in 36% and liver toxicity in 20% of patients. One toxic death occurred (2.5%). Objective responses were obtained in 36 of 39 patients (92%) with complete remissions (CR) in 24 patients (61.5%) and partial remissions (PR) in 12 (30.7%). Median observation time for surviving patients was 23.3 months (range 3.4-52.3). The probabilities of overall, event-free and relapse-free survival at 2 years are 62, 39 and 55%, respectively. Patients with primary refractory disease or resistant relapse had a poor prognosis. High-dose carboplatin, etoposide and ifosfamide plus autologous stem cell rescue represents an effective, potentially curative salvage treatment with acceptable toxicities.

Herpes simplex infection of the jejunum occurring in the early post-transplantation period.

Reactivation of infections with herpes viruses is a frequent and major cause of morbidity after bone marrow transplantation. In this case report we stress that HSV infections of the colon and small intestine should be considered in the differential diagnosis of diarrhea and intestinal bleeding in the early post-transplantation period. Severe acute GVHD and subsequent intensive immunosuppressive treatment may increase the risk for reactivation of HSV infection particularly in situations in which acyclovir prophylaxis has been omitted.