Indications and donor source of hematopoietic stem cell transplants in Europe 1993: report from the European Group for Blood and Marrow Transplantation (EBMT)

This report details the evolution of bone marrow transplantation in Europe over a 20-year period. In 1973, 8 teams undertook a total of 16 allogeneic bone marrow transplants; in 1983, 97 teams performed 1353 transplants. In 1993, the numbers had risen to 260 teams and 7737 transplants. Donor source in 3092 cases was an allogeneic donor (2464 HLA-identical sibling transplants, 147 non-identical family donor transplants, 25 twin donor transplants and 456 unrelated donor transplants). For 4645 patients the transplant was autologous (2450 autologous bone marrow transplants, 1830 autologous peripheral blood stem cell transplants and 365 combined autologous peripheral blood and bone marrow transplants). Indications for transplants in 1993 were leukemias in 3419 patients (44%; 2332 allogeneic, 1087 autologous), lymphoproliferative disorders in 2666 patients (34%; 197 allogeneic, 2469 autologous), solid tumors in 1077 patients (14%; 9 allogeneic, 1068 autologous), aplastic anemia in 251 patients (3%; 250 allogeneic, 1 autologous), inborn errors in 244 patients (3%; 242 allogeneic, 2 autologous) and miscellaneous disorders in 80 patients (1%; 62 allogeneic, 18 autologous). These data illustrate the increase of hematopoietic stem cell transplants as a therapeutic modality over the last 20 years in Europe.     

Methylsulfonyl metabolites of PCBs and DDE in human tissues

More than 15 years passed since bone marrow transplantation (BMT) have first introduced to the field of treatment of pediatric cancer. During this period, technology and modality of BMT have been improved steadily and several kinds of hemopoietic stem cell transplantation, for instance, allogeneic BMT from related or unrelated donor, unpurged or purged autologous BMT by 4-hydroperoxycyclophosphamide (4-HC) or magnetic immuno-beads, allogeneic or autologous peripheral blood stem cell transplantation and cord blood stem cell transplantation became available. Now we can choose the most suitable transplantation method for each patient from our repertory according to the patient's condition. In this article, treatment result of allogeneic BMT and 4-HC purged autologous BMT for children with acute leukemia and several kinds of hematopoietic stem cell transplantation for children with solid tumors in my hospital were reported.     

Itraconazole responsive tinea capitis in an HIV-infected child

Cytopenias following bone marrow transplantation may be severe and life-threatening. These have been described post-allogeneic Klumpp, 1991: Bone Marrow Transplant 8:159-171. or post-autologous bone marrow transplants Khouri et al., 1994: J Clin Oncol 12:748-758. as well as with peripheral blood stem cell transplantation Klumpp et al., 1992: Am J Hematol 41:215-217. It can be immune mediated, associated on occasions with graft-versus-host disease (GVHD) Anasetti et al., 1989: Blood 4:1054-1058; however, in most cases, the underlying mechanism is uncertain. The treatment of post-transplant cytopenias is not well established, and they are often refractory to immunosuppressive therapy with steroids. Herein we describe two cases of neutropenia after allogeneic bone marrow transplantation that improved after therapy with high-dose intravenous immunoglobulin.     

Serum interleukin-3 levels following autologous or allogeneic bone marrow transplantation: effects of T-cell depletion, blood stem cell infusion, and hematopoietic growth factor treatment

Engraftment of marrow following autologous or allogeneic bone marrow transplantation (BMT) may be influenced by quantity and function of stem cells. T lymphocytes, supporting microenvironmental cells, and hematopoietic growth factors (HGF). To elucidate the physiologic role of interleukin-3 (IL-3) in the engraftment process, serum IL-3 levels were measured in over 400 samples from 77 transplant recipients before and for up to 3 weeks following transplantation using a novel enzyme-linked immunoabsorbent assay (ELISA) with a sensitivity of > or = 78 pg/mL. Thirty-seven patients received two to three log T-cell-depleted allografts. In the remaining 40 patients (18 autologous marrow, 12 allogeneic marrow, and 10 autologous peripheral blood [PB] stem cell), T cells were not depleted (non-TCD) from the grafts. A burst of IL-3 (peak levels, 1,500 to 6,000 pg/mL) was detected in the immediate posttransplant period between day 0 and day 14 in all non-TCD recipients and in 21 of 37 (57%) of TCD recipients. A strong inverse relationship between IL-3 levels and absolute neutrophil count (ANC) was observed in both non-TCD recipients (r = -.796) and in TCD recipients (r = -.897). However, both peak IL-3 levels and mean IL-3 levels from day 0 through 14 were significantly lower in TCD recipients compared with either autologous or unmodified allogeneic marrow recipients (P < .01). The lowest peak or mean day 0 through 14 IL-3 levels were observed in matched related recipients undergoing the most aggressive (2.5 to 3.0 log) T-cell-depleted BMT. Autografted patients receiving blood stem cell transplants alone or posttransplant granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) also had significantly lower peak IL-3 levels (P < .01). In patients receiving TCD grafts, administration of antithymocyte globulin (ATG) posttransplant significantly increased peak IL-3 levels compared with patients not treated with ATG (P < .04). This study shows that endogenous release of IL-3 is strongly associated with myeloid engraftment and inversely related to ANC. Removal of T lymphocytes from donor marrow or acceleration of engraftment by use of stem cells or growth factors appears to blunt the endogenous release of IL-3 whereas use of ATG posttransplant increases IL-3 release.     

Myeloid leukemia and myelodysplastic syndrome relapsing as granulocytic sarcoma (chloroma) after allogeneic bone marrow transplantation

Of 229 consecutive patients receiving allogeneic blood or bone marrow stem cell transplants for acute myeloid leukemia, chronic myeloid leukemia, or myelodysplastic syndrome between 1974 and 1996, 52 patients relapsed. The original tumor recurred as granulocytic sarcoma (chloroma) in three patients (1.3%). Chloroma was found in the ovary in two patients and in the central nervous system in one patient. None of these three patients had experienced > or = grade II acute or more than limited chronic graft-versus-host disease. The intervals between transplantation and recurrence with chloroma were 2, 6, and 13 years. Two patients received a second transplant, and all three died of treatment sequelae.     

Autologous stem cell transplantation. From bone marrow to selected blood stem cells: 100 consecutive procedures at a single center

One hundred consecutive autologous stem cell transplants are reported: Non-Hodgkin's lymphoma 51 cases, Hodgkin's disease 27 cases, acute leukaemia 14 cases, multiple myeloma seven cases and chronic myeloid leukaemia one case. Most patients were in their second or later remission. The overall three-year survival for all patients was 60% and the three-year disease-free survival was 50% for lymphoma patients and 30% for acute leukaemia patients. The dominant source of stem cells was bone marrow during 1993, but from 1994 it has been peripheral blood, now totalling 33 cases. There were 12 toxic deaths, all among patients who were heavily treated before bone marrow harvest and transplantation. The patients transplanted with blood stem cells had significantly shorter duration of pancytopenia, and hospital stay, but their disease-free survival was not longer than that of a comparable group of bone marrow transplanted patients. Six patients were transplanted with purified CD34+ cells (selected by avidity column (Ceprate (R)), and had duration of thrombocytopenia and hospital stay similar to the patients transplanted with unmanipulated blood stem cells, but slightly longer duration of neutropenia. We conclude that high-dose therapy with autologous stem cell transplantation in not too heavily pretreated patients is a safe procedure irrespective of the source of stem cells.     

Prevention of onset in an insulin-dependent diabetes mellitus model, NOD mice, by oral feeding of Lactobacillus casei

Allogeneic bone marrow transplantation is the only currently available curative treatment for myelodysplastic syndromes (MDSs) but can be used only in the minority of patients (10%) who are younger than 55 years or so and for whom an HLA-identical donor is available. Each year in Europe, about 100 patients with MDSs receive an autologous bone marrow transplant. This procedure is usually indicated as first-line treatment, except in patients without excess of blasts or complex cytogenetic abnormalities. In forms with excess of blasts, chemotherapy prior to bone marrow transplantation deserves discussion. Autologous bone marrow transplants or the more recent technique involving transplantation of autologous peripheral stem cells can be considered in patients who have achieved a complete remission under aggressive chemotherapy. This method has been followed by higher recurrence rates in patients with MDSs than in those with de novo acute myeloblastic leukemia, and randomized studies are under way to compare it with aggressive maintenance chemotherapy.     

Thymus transplantation, a critical factor for correction of autoimmune disease in aging MRL/+mice

MRL/MP-+/+ (MRL/+) mice develop pancreatitis and sialoadenitis after they reach 7 months of age. Conventional bone marrow transplantation has been found to be ineffective in the treatment of these forms of apparent autoimmune disease. Old MRL/+ mice show a dramatic thymic involution with age. Hematolymphoid reconstitution is incomplete when fetal liver cells (as a source of hemopoietic stem cells) plus fetal bone (FB; which is used to recruit stromal cells) are transplanted from immunologically normal C57BL/6 donor mice to MRL/+ female recipients. Embryonic thymus from allogeneic C57BL/6 donors was therefore engrafted along with either bone marrow or fetal hematopoietic cells (FHCs) plus fragments of adult or fetal bone. More than seventy percent of old MRL/+ mice (> 7 months) that had been given a fetal thymus (FT) transplant plus either bone marrow or FHCs and also bone fragments survived more than 100 days after treatment. The mice that received FHCs, FB, plus FT from allogeneic donors developed normal T cell and B cell functions. Serum amylase levels decreased in these mice whereas they increased in the mice that received FHCs and FB but not FT. The pancreatitis and sialoadenitis already present at the time of transplantations were fully corrected according to histological analysis by transplants of allogeneic FHCs, FB and FT in the MRL/+ mice. These findings are taken as an experimental indication that perhaps stem cell transplants along with FT grafts might represent a useful strategy for treatment of autoimmune diseases in aged humans.     

Bilateral breast reconstruction in very thin patients with extended free TRAM flaps

High dose therapy and stem cell transplantation is increasingly being used for treatment of CLL. The present article summarizes available results reported in literature on the use of high dose therapy followed by allogeneic or autologous hemopoietic precursor infusion. Transplant procedures seem a feasible approach, especially autografts, while allogeneic transplant has been associated with a higher mortality rate. Interesting clinical/biological results have been reported for both allogeneic and autologous transplants but prospective large clinical trials are needed to establish their real value. We consider important issues of stem cell transplantation in CLL patients, such as the kind of transplant (allogeneic vs autologous), the optimum timing, the selection of patients, the value and type of purging and, above all, impact on survival.     

A multicenter study of platelet recovery and utilization in patients after myeloablative therapy and hematopoietic stem cell transplantation

An observational study was conducted at 18 transplant centers in the United States and Canada to characterize the platelet recovery of patients receiving myeloablative therapy and stem cell transplantation and to determine the clinical variables influencing recovery, determine platelet utilization and cost, and incidence of hemorrhagic events. The study included 789 evaluable patients transplanted in 1995. Clinical, laboratory, and outcome data were obtained from the medical records. Variables associated with accelerated recovery in multivariate models included (1) higher CD34 count; (2) higher platelet count at the start of myeloablative therapy; (3) graft from an HLA-identical sibling donor; and (4) prior stem cell transplant. Variables associated with delayed recovery were (1) prior radiation therapy; (2) posttransplant fever; (3) hepatic veno-occlusive disease; and (4) use of posttransplant growth factors. Disease type also influenced recovery. Recipients of peripheral blood stem cells (PBSC) had faster recovery and fewer platelet transfusion days than recipients of bone marrow (BM). The estimated average 60-day platelet transfusion cost per patient was $4,000 for autologous PBSC and $11,000 for allogeneic BM transplants. It was found that 11% of all patients had a significant hemorrhagic event during the first 60 days posttransplant, contributing to death in 2% of patients. In conclusion, clinical variables influencing platelet recovery should be considered in the design and interpretation of clinical strategies to accelerate recovery. Enhancing platelet recovery is not likely to have a significant impact on 60-day mortality but could significantly decrease health care costs and potentially improve patient quality of life.     

Giant cell fibroblastoma associated with dermatofibrosarcoma protuberans: a case report

Umbilical cord blood (UCB) was disclosed to possess the proliferative capacity containing hematopoietic progenitors and has recently been applied for allogeneic transplantation as an attractive alternative to bone marrow or peripheral blood stem cells. UCB contains similar and higher proportions of immature hematopoietic progenitors, compared to bone marrow stem cells, although the number of collectable cells is limited. The yield of collectable UCB volume ranges from 70 to 150 ml. The colony formation of CFU-Mix of UCB was higher, but that of CFU-GM and CFU-E was lower, compared to those of bone marrow. The analyses of expression of differentiation antigens and adhesion molecules on CD34+ cells of UCB by flow cytometer, revealed that the coexpression rates of CD38 and CD44 on CD34+ cells were almost the same, but the mean fluorescence intensity of those was low compared to adult bone marrow. These results indicate that UCB contains more primitive hematopoietic progenitors. UCB transplantation has greater advantages of lower incidences of graft versus host disease, and unlimited number of donors compared with other allogeneic transplantation would widen the indication of transplantation by technical and methodological development.     

Triploidy: antenatal sonographic features with post-mortem correlation

The CD34 antigen is expressed by human hematopoietic progenitor and stem cells. These cells are capable of reconstituting marrow function after marrow-ablative chemo-radiotherapy. Several different technologies have been developed for the separation of CD34+ cells from bone marrow or peripheral blood stem cell (PBSC) components. We used an immunomagnetic separation technique to enrich CD34+ cells from PBSC components in anticipation of autologous transplantation for patients with B lymphoid malignancies. Twenty-nine patients enrolled on this study and received mobilization chemotherapy followed by G-CSF. Of these, 21 achieved a peripheral blood CD34+ cell level of at least 2.0 x 10(4)/l required by protocol for separation of the stem cell components. A median of three components per patient was collected for processing. The average CD34+ cell concentration in the components after apheresis was 1.0 +/- 1.2%. After the CD34+ cell selection, the enriched components contained 0.6 +/- 0.6% of the starting nucleated cells. The recovery of CD34+ cells, however, averaged 58.4 +/- 19.2% of the starting cell number, with a purity of 90.8 +/- 6.5%. Overall depletion of CD34- cells was 99.96 +/- 0.06%. Nineteen patients were treated with marrow-ablative conditioning regimens and received an average of 6.2 +/- 2.0 x 10(6) CD34+ cells/kg body weight. These patients recovered to an ANC >0.5 x 10(9)/l at a median of 11 days (range 8-14), and platelet transfusion independence at a median of 9 days (range 5-13). Four patients died of transplant-related complications or relapse before 100 days after transplantation. No patient required infusion of unseparated cells because of failure of sustained bone marrow function. These data demonstrate that peripheral blood-derived CD34+ cells enriched by use of an immunomagnetic separation technique are capable of rapid engraftment after autologous transplantation.     

The mechanisms involved in the impairment of hematopoiesis after autologous bone marrow transplantation

Hematopoiesis after autologous bone marrow transplantation (BMT) is characterized by a prolonged and severe deficiency of marrow progenitors for several years, especially of erythroid and megakaryocyte progenitors, while the peripheral blood cells and marrow cellularity have reached relatively normal values within a few weeks. These anomalies are comparable to those reported for allogeneic BMT, despite the absence of any allo-immune reaction or post-graft immunosuppressive therapy. Post-graft hematopoietic impairment is the consequence of quantitative and qualitative changes involving both stem cell and stromal compartments which are expressed by an impaired capacity of stem cell self-renewal and commitment towards erythroid and megakaryocytic lineages. Besides the toxicity of conditioning regimens, hematopoietic reconstitution using autologous grafts is particularly dependent on a combination of factors related to the patient, such as underlying disease and pre-graft chemotherapy regimens, and to the graft processing itself, such as in vitro purging with chemotherapeutic agents.     

Preoperative portal embolization: an effective means for inducing hypertrophy of the healthy liver and increasing indications for hepatic resection]

BACKGROUND: This study was carried out to investigate the efficacy and safety of high-dose chemotherapy (HDC) for the treatment of patients with advanced testicular cancer. METHODS: Seven patients were treated with high-dose carboplatin, etoposide, and ifosfamide followed by autologous blood stem cell transplantation. One patient received 1 cycle, 4 patients received 2 cycles, and 2 patients received 3 cycles of HDC. We performed a total of 15 autologous blood stem cell transplantations: 8 with autologous bone marrow; 6 with peripheral blood stem cells; and 1 with peripheral blood stem cells in addition to autologous bone marrow. RESULTS: Four of the 7 patients achieved a pathologic complete response via early use of HDC and additional salvage surgery. All 4 patients are still alive without evidence of disease at 12, 30, 33, and 54 months, respectively. One patient is alive with active disease at 35 months. Two patients refractory to conventional chemotherapy died of progressive disease at 5 and 27 months, respectively. The hematologic recovery after HDC was rapid, and peripheral blood stem cells tended to have shorter hematologic recovery compared with those from autologous bone marrow, although the difference was not significant. Nonhematologic toxicity was usually mild and manageable. CONCLUSION: High-dose chemotherapy, followed by autologous blood stem cell transplantation, may be safe and effective for patients with advanced testicular cancer, particularly when early use of HDC is conducted for chemotherapy-sensitive patients. A further large, long-term, follow-up study will be needed to define the role of HDC.     

The role of blood stem cells in hematopoietic cell renewal

It has been the purpose of this keynote address to review available evidence for the notion that the stem and progenitor cells circulating in the peripheral blood play a decisive role in the homeostasis of blood cell formation distributed throughout dozens of bone marrow units in the skeleton. Furthermore, if this notion is correct, one could speculate that the quantity and quality of stem and progenitor cells in the blood should reflect the functional state of the hematopoietic stem cell system throughout the skeletal bone marrow and provide a new tool for the evaluation of alteration in blood cell production. On this basis, the following questions are considered: A) What do we know about the quality and quantity of blood stem cells in steady-state conditions? B) In what way do blood stem cells respond to perturbations of the "steady-state" of blood cell formation? C) Which role do blood stem cells play during hemopoietic development assuming that the establishment of bone marrow hemopoiesis requires the "seeding" of blood stem cells into an appropriate cellular environment? D) What is the role of blood stem cells in hemopoietic regeneration after partial body irradiation with a small volume of marrow (and hence stem cells) protected? and E) What are the mechanisms and/or kinetics of hemopoietic recovery if stem cells introduced into the circulation were collected from exogenous (autologous or allogeneic) sources? In this review presentation, experimental work of our group and of other members of the scientific community is summarized. It becomes obvious that blood stem and progenitor cells play a key role in hematopoietic homeostasis. Furthermore, their physiology and pathophysiology deserve rigorous experimental studies in order to develop a novel tool in the diagnosis and prognosis of neoplastic and non-neoplastic disorders of blood cell formation.     

Indications, technique and risks in bone marrow transplantation in adulthood

The option of bone marrow transplantation (BMT) significantly improved prognosis of adult patients with hematologic malignancies aged less than 50 years. Allogeneic BMT using the marrow of an HLA-identical family member still provides the most effective method of BMT. Conventional indications for this form of BMT are chronic myeloid leukemia (CML), acute leukemias presenting with adverse risk factors, myelodysplastic syndromes and severe aplastic anemia. If performed early in the disease course (e.g. during the chronic phase of CML or first remission of acute leukemia and MDS) allogeneic BMT cures 50 to 60% of patients. About 20% die of therapy related complications, e.g. graft versus host disease (GvHD), fatal infections or venoocclusive disease of the liver (VOD) and about 20% of patients succumb to relapse of their hematologic disorder. 80% presenting with severe aplastic anemia can be cured, if allogeneic BMT is performed soon after diagnosis without previous immunosuppressive therapy and blood transfusions. BMT with the marrow of a matched unrelated donor or autologous BMT are increasingly used as alternative procedures. A rate of lethal complications as high as 50% hinders rapid extension of BMT with unrelated donors. Therefore, this form of BMT should be restricted to young patients with leukemias, who cannot achieve long-term remission with conventional chemotherapy (in case of acute leukemias) or alpha-interferon (in case of CML). Reconstitution of hematopoiesis is more rapid after peripheral blood stem cell transplantation (PBSCT) compared with autologous BMT. Therefore, PBSCT will replace autologous BMT in most cases. Most favourable results of PBSCT have been reported in patients with malignant lymphomas after relapse or inferior response to primary induction therapy. Due to the higher relapse rate autologous BMT is inferior to allogeneic BMT in leukemia patients. Trials are required to clarify the potential role of myeloablative therapy with stem cell support in the treatment of patients with solid tumors. Many of the preliminary results already published are unsatisfactory and data of larger trials are still lacking. Therefore, BMT or PBSCT cannot be recommended generally for the therapy of patients with solid tumors.     

Expression of interleukin-6 and interleukin-6 receptors in human granulosa lutein cells

Prolonged isolated thrombocytopenia, defined as recovery of other cell counts with continuous dependence on platelet transfusions for greater than 90 days after hematopoietic stem cell transplantation (HSCT), develops in approximately 5% of patients who undergo HSCT. Although the clinical conditions associated with prolonged isolated thrombocytopenia have been studied, a systematic review of bone marrow biopsies has not been performed and the pathophysiologic basis has not been defined. We reviewed all HSCT at one center from 1990 to 1995 (n = 454) and found 12 cases that met criteria for prolonged isolated thrombocytopenia (incidence = 12/454 or 3%). Bone marrow core biopsies from 12 patients with prolonged isolated thrombocytopenia were reviewed to determine cellularity, numbers of megakaryocytes, the presence of atypical forms, and clusters of megakaryocytes. These marrow megakaryocyte counts were compared to age and disease matched controls, and 11 normal donors. Patients (aged 1-56 years, mean 32 years) who underwent HSCT (four sibling HLA-identical, five autologous bone marrow, three autologous peripheral stem cell) with prolonged isolated thrombocytopenia had a statistically significant lower absolute megakaryocyte count in bone marrow biopsies performed before transplantation and more than 30 days after transplantation compared to control patients (aged 4 months to 50 years, mean 31 years) who underwent HSCT (four sibling HLA-identical, four autologous bone marrow, four autologous peripheral stem cell) for similar conditions. No apparent differences were seen in size of megakaryocytes, nuclear-cytoplasmic ratios, or clustering of megakaryocytes. Overall marrow cellularities were similar in the three groups. These findings suggest that decreased differentiation of megakaryocytes from stem cells, rather than ineffective platelet production or peripheral destruction of platelets, causes prolonged isolated thrombocytopenia in HSCT patients. Low megakaryocyte counts prior to HSCT may be a useful prognostic indicator, as this feature was associated with the development of prolonged isolated thrombocytopenia.     

The value of sequential CD 34 measurement for carrying out stem cell pheresis

The recent significant improvement in disease-free survival in patients with certain haematological malignancies is due to high-dose chemotherapy and subsequent autologous bone marrow and/or stem cell transplantation. The proliferation and egression of stem cells into the peripheral blood must first be stimulated by defined chemotherapy and/or by administration of cytokines. However, the increase of circulating stem cells in peripheral blood is limited to only a few days. By immunologically analysing white blood cells for the expression of the surface antigen CD 34 it is possible to calculate the numbers of haematopoietic progenitor cells. Thus, besides monitoring haematopoietic recovery, the estimation of CD34+ cells in the peripheral blood can be used to indicate the optimal time point for stem cell collection. Two to four stem cell pheresis (one per day) may then yield sufficient stem cells to enable the safe and rapid reconstitution of haematopoiesis following supralethal chemotherapy.     

Toxicity, pharmacology and feasibility of administration of PEG-L-asparaginase as consolidation therapy in patients undergoing bone marrow transplantation for acute lymphoblastic leukemia

We attempted to administer PEG-L-asparaginase (PEG-L-A) following hematologic recovery to 38 patients undergoing autologous or allogeneic marrow transplantation for acute lymphoblastic leukemia (ALL). Twenty-four patients (12 of 22 receiving allogeneic and 12 of 16 receiving autologous transplants) received between one and 12 doses of PEG-L-A, including nine who completed the planned 12 doses of therapy. The toxicities encountered were similar to those observed in non-transplanted patients undergoing therapy with PEG-L-A and included allergic reactions, pancreatitis, weight loss, hypoalbuminemia, and low levels of anti-thrombin III. Of the 24 who received the drug, eight remain in remission. Of 12 patients in second remission at the time of transplantation who received PEG-L-A, five of seven who received allogeneic and two of five who received autologous transplants remain in remission, 16+ to 46+ months from transplant. While PEG-L-A could be administered to most of the patients undergoing marrow transplantation for ALL, most patients either relapsed while receiving the drug or developed toxicities which resulted in abbreviated courses. At this time, we cannot recommend PEG-L-A as single agent, post-BMT chemotherapy.     

Therapy of highly malignant non-Hodgkin lymphoma with high-dose chemotherapy and stem cell transplantation

Patients with intermediate or high-grade non-Hodgkin's lymphoma are rarely cured of their disease after the failure of conventional therapy. High-dose chemotherapy followed by transplantation of either autologous marrow (ABMT) or peripheral stem cells (PBSCT) offers such patients a new possibility of cure. To patients younger than 60 years and without contraindications high-dose chemotherapy should be offered in case of relapse and bad prognosis. The PARMA-study demonstrated, that high-dose chemotherapy with subsequent autologous stem cell transplants is superior to conventional chemotherapy for relapsing patients. However high-dose chemotherapy in first complete or partial remission followed by ABMT and PBSCT as post-remission therapy for adult NHL has yielded only similar results randomized to those achieved with conventional chemotherapy in several prospectively studies. This approach should be limited to patients with bad prognostic factors (high-intermediate or high-risk groups according to the International Prognostic Factor Project). The success of ABMT and PBSCT in treating these diseases mandates exploration of the best high-dose chemotherapy, the use of autologous or allogenic bone marrow resp. peripheral stem cell for haematopoietic reconstitution and technical aspects such as purging of tumor cells, the short- and long-term transplant-related mortality continues to be a major concern.