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At least 919 records · Page 51Linked to original sources
PubMed2005

Post-transplant lymphoproliferative disorders after live donor renal transplantation.

The development of post-transplant lymphoproliferative disorders (PTLD) is a well-recognized complication of solid organ transplantation in patients receiving immunosuppressive therapy. The literature on PTLD in live renal allograft recipients is scarce and most of the data pertains to PTLD in cadaveric transplants. As live donor grafts form the mainstay of transplantation programme in India, this study was carried out to define the profile of PTLD in live donor renal allograft recipients. On retrospective evaluation, nine cases of PTLD amongst 1700 live donor allograft recipients from January 1989 to August 2004, were detected at a tertiary care hospital in north India. The clinicopathological features of these cases were evaluated. Mean age at diagnosis of PTLD was 38 yr with median post-transplant latency period of 7 yr. All cases were from extra-renal sites, five being in ileum/jejunum, three in retroperitoneal lymph nodes and one in epididymus. All cases received cyclosporin, azathioprine and prednisolone in varying combinations as immunosuppressive therapy. One case was treated for rejection by anti-thymocyte globulin. Seven patients were seronegative for Epstein-Barr virus at the time of diagnosis. All were B-cell monomorphic PTLD, classifiable as B-cell diffuse large cell lymphomas, with five extranodal and three nodal lymphomas. Management included reduction in immunosuppression, acyclovir therapy, surgical excision and chemotherapy. On follow-up, four patients died, two presented with recurrence, two were in remission and one was lost to follow-up. This study comprising of live related/unrelated renal allograft recipients observed late onset high grade monomorphic PTLD with paucity of early onset polymorphic lesions. Long post-transplant latency period, aggressive behaviour and poor response to treatment necessitate long-term cancer surveillance to facilitate early detection and newer therapeutic strategies to improve the outcome in these patients.

Adult↗
PubMed2005

HCV infection of the transplanted liver: changing CD81 and HVR1 variants immediately after liver transplantation.

The second envelope protein at hypervariable region 1 (HVR1) has been implicated in contributing to hepatitis C virus (HCV)-host cell interactions and CD81 (a multifunctional protein) has been demonstrated to act as a cell surface receptor for HCV and may interact directly with HVR1. The purpose of the current study was to determine if certain HVR1 quasispecies variants more effectively associate with and infect allografts after liver transplantation than other HVR1 variants and whether CD81 receptor expression changes after transplantation. Blood and allograft samples were obtained from the peritransplant period in seven patients. Clones of RT-PCR product were directly sequenced to identify HVR1 quasispecies variants. Explanted liver and serial allograft biopsies in recipients with HCV were examined by immunohistochemistry (IHC) for CD81 expression. Examination of HVR1 sequences demonstrated that only a fraction of the quasispecies variants recovered from each patient's blood sampled immediately prior to transplantation associated with and infected the allografts. Genetic diversity at HVR1 decreased with reperfusion but did not significantly decrease with infection. Expression of CD81 varied during the immediate post-transplant period. In conclusion, HVR1 quasispecies variants differentially associate with, and infect allografts, after liver transplantation. Additionally, allografts express variable amounts of CD81 after transplantation.

Amino Acid Sequence↗
PubMed2006

Recurrent hepatitis C post-transplantation: where are we now and where do we go from here? A report from the Canadian transplant hepatology workshop.

Approximately 400 liver transplants are performed in Canada every year and close to 6000 per year in the United States. Forty per cent to 45% of all liver transplants are performed for patients with underlying hepatitis C virus (HCV)-related liver disease. These patients have a different natural history, new complication risks and different treatment efficacy than nontransplant HCV patients. Every effort must be made to identify those patients at highest risk for progressive liver disease post-transplant. Recurrent HCV is an Achilles' heel to transplant hepatology. The true natural history of this disease is only starting to unravel and many questions remain unanswered on the optimal management of these patients after liver transplantation. The present report summarizes the literature and ongoing research needs that are specific to HCV-related liver transplantation.

Canada↗
PubMed1980

Post-transplantation development of malignant lymphoma, an experimental model: syngeneic lymph node transplants.

Previously, malignant lymphomas in mice have been found to be the late sequelae of the autologous transplantation of skin grafts pretreated with CO(2); these did not occur with grafts cultured in air alone. The clinical result in this autologous system reflects environmental differences in vitro (Goldsmith & Narvaez 1975). In the present study the syngeneic transplantation in BALB/c mice of lymph node tissue resulted in the late appearance of malignant lymphomas (48-69%), irrespective of the pretransplantation treatment of the grafts. Lymph node grafts were exposed to three different environments before transplantation into syngeneic hosts: (1) to culture in air (24 hours); (2) to culture in an atmosphere of 45% CO(2) in air (24 hours); (3) direct transplantation without in vitro exposure. Transplantation of these three groups of differently treated grafts was followed by the same clinical results in their recipients. These were: (1) The development of lymphoma whereas the spontaneous incidence was zero. (2) The proliferation of T-lymphocytes in the spleen; the incidence of this abnormality correlates with the lymphoma incidence. (3) A higher than normal occurence of immune-associated lesions (amyloidosis, interstitial nephritis and myocarditis). Both syngeneic and autologous transplantations may serve as animal models for the study of clinical malignant lymphoma.

Animals↗
PubMedDate not supplied

Fetal neocortical transplants grafted into neocortical lesion cavities made in newborn rats: an analysis of transplant integration with the host brain.

Fetal neocortical transplants placed into frontal cortex aspiration lesion cavities in newborn rats have been shown to survive and exchange connections with the host brain. To further study the afferent innervation of such transplants, enzyme- and immunohistochemical techniques were employed to examine the distribution of cholinergic, catecholaminergic and serotonergic fibers within the transplants, and radiochemical enzyme assays and high performance liquid chromatography were used to determine the content of neurotransmitter markers for these same fiber systems. To examine functional integration of the transplanted neurons in terms of activation of molecular signaling systems, the graft recipient animals were exposed to a novel open field environment. This behavioral testing paradigm is known to induce c-fos mRNA and Fos protein within several areas of the normal brain, including the sensorimotor cortex. Subsequent detection of the induction of this particular immediate early gene (transcription as well as translation) in the grafts would gene (transcription as well as translation) in the grafts would accordingly indicate genomic activation and therefore functional integration at the level of molecular signaling systems. Our results showed that these global fiber systems are distributed evenly throughout the extent of three mo old neocortical grafts and that the content of transmitter-related markers for these systems do not differ significantly from control cortex. Open field exposure of the grafted animals resulted in c-fos mRNA and Fos protein expression of cells distributed throughout the transplants. We conclude that the "global" fiber system innervation of neocortical transplants placed into newborn rats is similar to the innervation of normal cortex and that grafted neurons respond to host brain activation at the level of molecular signaling systems.

Animals↗
PubMed2004

Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation.

Single nucleotide polymorphisms (SNPs) of the NOD2/CARD15 gene resulting in a diminished nuclear factor-kappaB (NF-kappaB) response to bacterial cell wall products have been associated with an increased incidence of Crohn disease. To assess a possible contribution of NOD2/CARD15 mutations to graft-versus-host disease (GvHD) and complications following allogeneic stem cell transplantation, we retrospectively typed DNA from donor/recipient pairs in 169 consecutive patients receiving transplants from related or unrelated donors. Mutated alleles were observed in 21% of patients and in 14% of donors. Cumulative incidence of 1-year, transplant-related mortality rose from 20% in donor/recipient pairs without mutated SNPs to 49% in pairs with recipient mutations (P =.03) and 59% in pairs with donor mutations (P <.005), and was highest in 12 pairs with mutated alleles in both donor and recipients (83%; P <.001). Similar associations were observed for severe overall and severe gastrointestinal GvHD. The impact of NOD2/CARD15 mutations was more prominent for HLA-identical sibling transplantations but was also observed in unrelated donor transplantation. Mutations proved to be independent risk factors for transplant-related mortality. Our findings indicate a major role of monocyte/macrophage dysfunction in the pathophysiology of GvHD and strongly suggest a future risk assessment or even donor selection through NOD2/CARD15 typing.

Adolescent↗
PubMed1981

Subcutaneous, isogeneic transplantation of duct-ligated pancreas in streptozotocin-diabetic mice. Relationships between carbohydrate tolerance and hormone content in transplant or host pancreas.

Mice with subcutaneous, isogeneic transplants of duct-ligated pancreas from either two or five donors displayed impaired glucose tolerance to gastric or intravenous glucose, or to an overnight fast followed by a 15-min meal of mouse food. Compared with peripheral insulin responses in normal controls, those of transplant recipients were less after gastric or intravenous glucose, but no different after the meal. Despite normalization of peak insulin levels in the peripheral circulation of isografted mice, glucose clearance was still impaired and this probably resulted, in part, from a relative insufficiency of insulin in the portal circulation. Results of glucose tolerance tests, after transplant recipients consumed a relatively small amount of food, suggested that near-normal glucose homeostasis may be present for these mice under normal feeding conditions. In mice that received incremental doses of streptozotocin, impaired glucose tolerance to a meal was observed if pancreatic insulin content fell below 26% of normal. We failed to show a similar relationship between glucose tolerance and pancreatic insulin content in transplant recipients since all showed impaired glucose tolerance. Despite the initial transplantation of different amounts of islet tissue, at termination insulin content (transplant plus endogenous pancreas) was essentially the same for all recipients, totaling 19-22% of that found in a normal mouse pancreas.

Animals↗
PubMed2005

Islet transplantation is associated with an improvement of cardiovascular function in type 1 diabetic kidney transplant patients.

OBJECTIVE: Cardiovascular mortality and morbidity are major problems in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to determine whether islet transplantation can improve cardiovascular function in these patients. RESEARCH DESIGN AND METHODS: We assessed various markers of cardiac function at baseline and 3 years later in a population of 42 type 1 diabetic patients with ESRD who received a kidney transplant. Seventeen patients then received an islet transplant that had persistent function as defined by long-term C-peptide secretion (kidney-islet group). Twenty-five patients did not receive a functioning islet transplant (kidney-only group). RESULTS: GHb levels were similar in the two groups, whereas the exogenous insulin requirement was lower in the kidney-islet group with persistent C-peptide secretion. Overall, cardiovascular parameters improved in the kidney-islet group, but not in the kidney-only group, with an improvement of ejection fraction (from 68.2 +/- 3.5% at baseline to 74.9 +/- 2.1% at 3 years posttransplantation, P < 0.05) and peak filling rate in end-diastolic volume (EDV) per second (from 3.87 +/- 0.25 to 4.20 +/- 0.37 EDV/s, P < 0.05). Time to peak filling rate remained stable in the kidney-islet group but worsened in the kidney-only group (P < 0.05). The kidney-islet group also showed a reduction of both QT dispersion (53.5 +/- 4.9 to 44.6 +/- 2.9 ms, P < 0.05) and corrected QT (QTc) dispersion (67.3 +/- 8.3 to 57.2 +/- 4.6 ms, P < 0.05) with higher erythrocytes Na(+)-K(+)-ATPase activity. In the kidney-islet group only, both atrial natriuretic peptide and brain natriuretic peptide levels decreased during the follow-up, with a stabilization of intima-media thickness. CONCLUSIONS: Our study showed that type 1 diabetic ESRD patients receiving a kidney transplant and a functioning islet transplant showed an improvement of cardiovascular function for up to 3 years of follow-up compared with the kidney-only group, who experienced an early failure of the islet graft or did not receive an islet graft.

Atrial Natriuretic Factor↗
PubMed1994

Prognostic factors in autologous stem cell transplantation for multiple myeloma: an EBMT Registry Study. European Group for Bone Marrow Transplantation.

Autologous bone marrow- and blood progenitor cell transplantation was performed in 130 patients with multiple myeloma in 16 European centers between 1986 and 1993. At the time of follow-up, 77 patients were alive and 53 were dead. Complete remission after transplantation was obtained in 47% of all patients. The actuarial survival at 65 months was 28%. The median duration of relapse-free survival among patients who were in complete remission after transplantation was 29 months. The following factors were predictive for longer survival and freedom of progression in a univariate analysis: Male sex, age less than 45 years, a low serum-beta-2-microglobulin value at diagnosis, prior administration of only one treatment regimen, response on conventional chemotherapy immediately pretransplant and the use of a preparative regimen including melphalan. The last factor, in addition to stage I disease at diagnosis, male sex and responsive disease immediately pretransplant, were also demonstrated as independent predictive variables for longer survival in a multivariate analysis. Progression-free survival was significantly better for patients who were in complete remission after transplantation, as compared to those with persisting signs of disease. We conclude that high-dose chemo-radiotherapy with autologous stem cell transplantation can induce long-term responses, primarily in younger, male patients with chemotherapy-responsive early disease. High-dose melphalan, as single drug or in combination, appeared to be superior to other regimens. The chance of being persistently disease-free seemed to be greatest for patients being in complete remission already before the transplantation.

Adult↗
PubMed1999

Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group.

We have analyzed factors influencing the outcome of 102 children with acute leukemia given a cord blood transplantation (CBT) and reported to the Eurocord Registry. Seventy patients with acute lymphoblastic and 32 with acute myeloid leukemia were given either a related (n = 42) or an unrelated (n = 60) CBT. Children given CBT during first or second complete remission were considered as belonging to the good-risk group (n = 66), whereas those who received a transplant in a more advanced stage of disease were assigned to the poor-risk group (n = 36). In the related group (RCBT), 12 of 42 patients received transplantation from an HLA-disparate donor, whereas in the unrelated group (UCBT) 54 of 60 received an HLA mismatched CBT. Kaplan-Meier estimates for neutrophil recovery at day 60 were 84% +/- 7% in RCBT and 79 +/- 6% in UCBT (P =.16). In multivariate analysis, the most important factor influencing neutrophil engraftment in UCBT was a nucleated cell dose infused greater than 3.7 x 10(7)/kg (P =.05, relative risk [RR] of 1.85, 95% confidence interval [CI]: 0.98-3.4). The incidence of grade II through IV acute graft-versus-host disease was 41% +/- 8% in the RCBT group and 37% +/- 6% in the UCBT group (P =.59). Kaplan-Meier estimates of 2-year event-free survival (EFS) after RCBT or UCBT were 39% +/- 8% and 30% +/- 7%, respectively (P =.19). In multivariate analysis, the most important factor influencing EFS was disease status at time of transplantation: good-risk patients had a 2-year EFS of 49% +/- 7% as compared to 8% +/- 5% in patients with more advanced disease (P =.0003, RR: 0.40, 95% CI: 0.24 to 0. 65). This was a consequence of both an increased 1-year transplant related mortality and a higher 2-year relapse rate in the poor-risk group (65% +/- 9% and 77% +/- 14%, respectively), as compared with good risk patients (34% +/- 6% and 31% +/- 9%, respectively). These data confirm that allogeneic CBT from either a related or an unrelated donor is a feasible procedure able to cure a significant proportion of children with acute leukemia, especially if transplanted in a favorable phase of disease.

Acute Disease↗
PubMed2002

European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.8. Bone disease.

GUIDELINES: A. All kidney-transplanted patients should undergo a systematic evaluation of their skeletal status, including pre-transplant history of renal osteodystrophy, history of fractures and plasma concentrations of calciotropic hormones and other parameters, and if possible measurement of bone mineral density (BMD). B. Glucocorticoid therapy should be given at the lowest possible dosage. As long as patients are receiving steroids, vitamin D treatment (ergocalciferol or 1,25-dihydroxyvitamin D) is highly recommended. C. Optimal prevention of bone disease by vitamin D treatment, sufficient calcium intake, sex hormone substitution and appropriate use of thiazide diuretics should be considered in all transplant patients. D. In established osteopenia, bisphosphonate treatment should be considered despite limited information in transplant recipients. E. Persistent tertiary hyperparathyroidism should be observed for 1 year after transplantation whenever possible to allow for a spontaneous involution. F. In patients with GFR <50 ml/min after transplantation, uraemic osteodystrophy should be prevented.

Bone Diseases↗
PubMed2002

[Perspectives for diabetes treatment through pancreas transplantation or islet transplantation].

Replacement of beta-cell function by transplantation of endocrine tissue is an alternative treatment for patients with complicated type 1 diabetes. Pancreas transplantation is presently the only treatment allowing to normalise glycemia without increasing the risk of hypoglycemia and to stop exogenous insulin-therapy. In spite of postoperative morbidity and mortality, pancreas transplantation improves quality of life, reduces cardiovascular risk factors and prolongs the life expectancy of diabetic patients with end-stage kidney failure. Islet transplantation is still an experimental procedure. However, the results obtained recently are a proof of principle that a cellular transplant can induce normoglycemia and insulin-independence in diabetic patients. In this review, the results and perspectives of pancreas and islet transplantation are discussed.

Diabetes Mellitus, Type 1↗
PubMed2005

Post-transplantation lymphoproliferative disorder of recipient origin in a boy with acute T-cell leukemia with detection of B-cell clonality 3 months before stem cell transplantation.

Post-transplantation lymphoproliferative disorder is an infrequent complication after hematopoietic stem cell transplantation. It is hypothesized that lack of T-cell surveillance following transplantation permits reactivation of latent EBV leading to polyclonal B-cell expansion and finally outgrowth of a predominant clone. Most cases are of donor origin. Here, we describe an 8-year old boy with early onset post-transplantation lymphoproliferative disorder following matched-unrelated stem cell transplantation for high-risk T-cell leukemia whose disease was unusual for two reasons. First, his B-cell clone was of host origin and, in contrast to the few PTLD of host origin described so far, not associated with autologous reconstitution. Secondly, using clonal analysis, we could retrospectively show that the B-cell clone emerged during consolidation chemotherapy for T-cell leukemia, 3 months before stem cell transplantation.

Antibodies, Monoclonal↗
PubMed2005

[Psychiatric problems in organ transplants: examples on the renal transplants from living relatives in Japan].

There has been an increase of the renal transplants from living relatives, making over 80% of all renal transplants thus leaving under 17% of them from cadaveric. As for living donors, anxiety and fear of physical vulnerability, possible complications/disabilities, and death/dying, triggered by the hospitalization; a sense of guilt and/or self-blame, or seeking for rewards/compensation, triggered by the transplant; and introjection, probiosis, regression, often presented post transplant. Depression is one of the significant problems among donors after failed transplant, but also even after successful renal transplant. It is called "paradoxical depression". As for recipients, anxiety, guilt feeling, anger are very common psychological issues before the operation. There are number of young adults who present marked anger and short temper, aggression and acting-out behavior as their defense mechanisms.

Depression↗
PubMed2006

The role of HLA mismatch, splenectomy and recipient Epstein-Barr virus seronegativity as risk factors in post-transplant lymphoproliferative disorder following allogeneic hematopoietic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Post-transplant lymphoproliferative disorder (PTLD) following allogeneic hematopioetic stem cell transplantation (HSCT) is a fulminant disease with high mortality. The objective of this study was to determine risk factors in PTLD following HSCT in order to identify high-risk patients for surveillance, prophylaxis and treatment. DESIGN AND METHODS: Five hundred and fifty-three HSCT patients transplanted at Karolinska University Hospital in Huddinge between 1996 and 2004 were investigated retrospectively and 14 cases of PTLD were identified. Diseased patients were evaluated concerning transplantation procedure, PTLD diagnosis, treatment and outcome. Factors significant in univariate analysis were included in logistic regression multivariate analysis. RESULTS: The incidence of PTLD was 2.5% and the median onset of PTLD was 78 days post-transplantation. Only two PTLD patients survived. The most common therapy was anti-B-lymphocyte antibodies. Statistical analysis showed HLA mismatch (p < 0.001), mismatch in Epstein-Barr virus (EBV) serology (p < 0.001) and splenectomy (p = 0.006) to be risk factors associated with PTLD. Indeed, among 387 patients with no risk factors only one developed PTLD (0.26%). Patients with one risk factor had a probability of developing PTLD of 8.2% and those with two risk factors, a probability of 35.7%. INTERPRETATION AND CONCLUSIONS: We propose a strategy for dealing with PTLD. Patients without risk factors need not be monitored routinely. HSCT patients with one or more risk factors should be monitored weekly by polymerase chain reaction of EBV DNA, and for patients with two or more risk factors EBV-specific cytotoxic T-lymphocytes should be held in readiness before initiating the transplantation procedure.

Epstein-Barr Virus Infections↗
PubMedDate not supplied

Heart-lung transplantation for cystic fibrosis and subsequent domino heart transplantation.

Between September 1984 and October 1988, 27 patients underwent combined heart-lung transplantation for treatment of end-stage respiratory disease caused by cystic fibrosis. The actuarial patient survival was 78% at 1 year and 72% at 2 years. Bacterial respiratory infections were common in the early postoperative period and necessitated vigorous medical therapy. The dose of cyclosporine required in these patients was higher than in conventional transplant recipients, and this contributed to an increased cost of postoperative care. Lung function was greatly improved after transplantation, and long-term survivors achieved an excellent quality of life. Lymphoproliferative disorders developed in two patients; these disorders regressed after a reduction in immunosuppression. Two patients required retransplantation: one because of obliterative bronchiolitis and the other because of recurrent respiratory infections associated with a moderate tracheal stenosis and severe deterioration in lung function. A modification of the technique used for heart-lung transplantation allowed 20 hearts from cystic fibrosis patients to be used for subsequent heart transplantation. Immediate heart function was satisfactory in all cases. The actuarial survival of the recipients of these domino heart transplants was 75% at 1 year. No coronary artery disease was present in the 12 patients who have undergone coronary angiography at 1 year.

Actuarial Analysis↗
PubMed1990

Graft-versus-leukemia in bone marrow transplantation. The Advisory Committee of the International Bone Marrow Transplant Registry.

We studied 2254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) in first remission, or chronic myelogenous leukemia (CML) in first chronic phase to determine whether graft-versus-leukemia (GvL) reactions are important in preventing leukemia recurrence after bone marrow transplantation. Four groups were investigated; recipients of non-T-cell depleted allografts without graft-versus-host disease (GvHD), recipients of non-T-cell depleted allografts with GvHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants compared with recipients of non-T-cell depleted allografts without GvHD, Decreased relapse was observed in recipients of non-T-cell depleted allografts with acute (relative risk 0.68, P = 0.03), chronic (relative risk, 0.43, P = 0.01), and both acute and chronic GvHD (relative risk 0.33, P = 0.0001). These data support an anti-leukemia effect of GvHD. AML patients receiving identical twin transplants had an increased probability of relapse (relative risk 2.58, P = 0.008) compared to allograft recipients without GvHD supporting an anti-leukemia effect of allografts independent of GvHD. CML patients receiving T-cell depleted transplants without GvHD had a higher probability of relapse (relative risk 6.91, P = 0.0001) than recipients of non-T-cell depleted allografts without GvHD. These data support an antileukemia effect independent of GvHD altered by T-cell depletion. These results indicate that much of the anti-leukemia effect of bone marrow transplants is related to immune factors rather than high-dose chemotherapy and/or radiation.

Bone Marrow Transplantation↗
PubMed1995

Autologous stem cell transplantation after first remission induction treatment in multiple myeloma: a report of the French Registry on autologous transplantation in multiple myeloma.

Eighteen French centers reported 133 autologous stem cell transplantations performed after first remission induction in multiple myeloma. The source of stem cell was marrow (81 cases), blood (51 cases) or marrow plus blood (1 case). The immediate outcome after transplantation was 49 (37%) complete remissions (CRs) (13 maintained, 36 achieved), 61 (46%) partial remissions, 17 failures and 5 toxic deaths. With a median follow-up of 35 months, the median remission duration was 33 months, the median time to treatment failure was 22 months. The median survival was 46 months overall, 54 months for the 103 patients responding to primary treatment, and 30 months for the 30 nonresponders. In univariate analysis, the outcome was influenced by age, Ig isotype, initial beta 2 microglobulin level, response to initial chemotherapy, plasma cell marrow involvement at the time of harvest, albumin and beta 2 microglobulin level at the time of transplantation, and CR achievement after transplantation. In multivariate analysis, the most important prognostic factor was the quality of response after transplantation. The conditioning regimen and the source of stem cell had no significant impact on immediate and long-term results. Maintenance therapy with interferon alpha did not appear to prolong remission duration or survival. Autologous stem cell transplantation is an effective consolidation for patients responding to primary treatment and a salvage therapy for some nonresponding patients. This approach has to be compared to conventional chemotherapy in prospective randomized studies. The critical impact of CR achievement on survival implies new strategies to increase the CR rate.

Adult↗