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1.
Leukemia ; 30(6): 1255-62, 2016 06.
Article in English | MEDLINE | ID: mdl-26859076

ABSTRACT

Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ∼88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-α only (n=3). The most common malignancies (n⩾4) were prostate, colorectal and lung cancer, non-Hodgkin's lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non-melanoma skin tumors was 0.88 (95% confidence interval (0.63-1.20)) for men and 1.06 (95% CI 0.69-1.55) for women. SIRs were between 0.49 (95% CI 0.13-1.34) for colorectal cancer in men and 4.29 (95% CI 1.09-11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time.


Subject(s)
Imatinib Mesylate/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Neoplasms, Second Primary/chemically induced , Protein Kinase Inhibitors/adverse effects , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/chemically induced , Female , Follow-Up Studies , Humans , Imatinib Mesylate/therapeutic use , Incidence , Interferon-alpha/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Lymphoma, Non-Hodgkin/chemically induced , Male , Middle Aged , Protein Kinase Inhibitors/therapeutic use , Sex Factors
2.
Leukemia ; 30(3): 562-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26464170

ABSTRACT

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.


Subject(s)
Antineoplastic Agents/therapeutic use , Hematopoietic Stem Cell Transplantation , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Protein Kinase Inhibitors/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Family , Female , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Prognosis , Prospective Studies , Remission Induction , Risk , Survival Analysis , Tissue Donors , Transplantation, Homologous , Treatment Outcome
3.
Leukemia ; 25(5): 808-13, 2011 May.
Article in English | MEDLINE | ID: mdl-21339758

ABSTRACT

Treatment options for adults with primary refractory acute myeloid leukaemia (PREF AML) are extremely limited. Although sibling allogeneic stem cell transplantation can result in long-term survival, most patients lack a matched family donor and are destined to die of refractory disease. Greater availability of unrelated donors and improvements in supportive care have increased the proportion of patients with PREF AML in whom allografting is technically feasible, but the outcome of unrelated donor transplantation in this population has not been studied. We therefore analysed overall survival in 168 patients with PREF AML, who underwent unrelated donor transplantation between 1994 and 2006. The 5-year overall survival for the whole group was 22%. In multivariate analysis, fewer than three courses of induction chemotherapy, a lower percentage of bone marrow blasts at transplant and patient cytomegalovirus seropositivity were associated with improved survival. This allowed the development of a scoring system that identified four groups with survival rates between 44±11% and 0%. This study demonstrates an important role for unrelated donor transplantation in the management of selected patients with PREF AML and confirms the importance of initiating an urgent unrelated donor search in patients with no matched sibling donor, who fail to respond to induction chemotherapy.


Subject(s)
Leukemia, Myeloid, Acute/therapy , Living Donors , Stem Cell Transplantation , Adolescent , Adult , Aged , Drug Resistance, Neoplasm , Female , Humans , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Remission Induction , Salvage Therapy , Survival Rate , Treatment Outcome , Young Adult
4.
Bone Marrow Transplant ; 45(2): 355-62, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19597418

ABSTRACT

A haematopoietic SCT (HSCT) can cause severe side effects, which may have a profound impact on a patient's life both physically and psychologically. Some studies have shown that physical activity has positive effects for inpatients after an HSCT. Therefore, the question arises whether a controlled exercise programme right from the beginning of the conditioning phase could help contribute to a patient's physical and psychological recovery. To evaluate the different effects of specific, moderate physical activities on the physical and psychological condition of HSCT patients we performed a controlled randomized study with 64 inpatients undergoing an allogeneic or autologous HSCT. The patients were randomly assigned to two groups. Although the training group took part in a specific programme of exercise therapy twice a day throughout the entire hospitalization phase, patients in the control group were offered the hospital's standard mobilization programme. The results of this study showed significant differences in favour of the training group regarding strength, endurance, lung function and quality of life. However, further studies are needed to confirm these results.


Subject(s)
Exercise Therapy/methods , Exercise Tolerance , Hematopoietic Stem Cell Transplantation/adverse effects , Adult , Female , Hematopoietic Stem Cell Transplantation/psychology , Humans , Lung/physiology , Male , Middle Aged , Quality of Life , Respiratory Physiological Phenomena
5.
Leukemia ; 21(9): 1945-51, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17611571

ABSTRACT

Hematopoietic cell transplantation (HCT) is an effective treatment for myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML). In this study, outcome of 593 patients with MDS/sAML after autologous and allogeneic HCT from a matched unrelated donor (MUD) were compared. A total of 167 (28%) patients received HCT from MUD without prior chemotherapy (MUD-U). The rest received HCT in first complete remission (CR1) (Autologous (Auto-CR1), n=290 (49%), HCT from MUD (MUD-CR1), n=136 (23%)). Survival at 3 years was best in MUD-CR1 (50%) compared to Auto-CR1 (41%) and MUD-U (40%) (P=0.01). Similarly, disease-free survival was 44% for MUD-CR1 compared to Auto-CR1 (28%) and MUD-U (34%) (P=0.03). Treatment-related mortality was 17% in Auto-CR1 compared to MUD-CR1 (38%) and MUD-U (49%) (P<0.001). Relapse for Auto-CR1 was 62% compared to 24 and 30% for MUD-CR1 and MUD-U, respectively (P<0.001). Outcome was best for patients with low tumor burden transplanted 6-12 months after diagnosis. Factors influencing outcome at 3 years were mainly significant in the first 6 months. Only, relapse after autologous HCT remained constant over time. Outcomes after allogeneic HCT in patients of 20-40 and >40 years were similar. Autologous and Allogeneic HCT from MUD offer the possibility of long-term survival to patients with MDS/sAML.


Subject(s)
Hematopoietic Stem Cell Transplantation/mortality , Leukemia, Myeloid/mortality , Leukemia, Myeloid/therapy , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/therapy , Acute Disease , Adolescent , Adult , Age Distribution , Aged , Disease-Free Survival , Female , Humans , Incidence , Male , Middle Aged , Recurrence , Retrospective Studies , Survival Analysis , Tissue Donors , Transplantation, Autologous , Transplantation, Homologous , Treatment Outcome
6.
Clin Transplant ; 21(1): 110-6, 2007.
Article in English | MEDLINE | ID: mdl-17302599

ABSTRACT

Allogeneic stem cell transplantation (SCT) is best performed with an HLA-identical sibling donor (matched related donor, MRD) to reduce the risk of early complications such as acute graft-vs.-host disease (aGvHD). However, as only about 30% of recipients have an MRD for this potentially curative approach, the use of family donors with one or two mismatches in the HLA-antigens (mismatch related donor, MMRD) or fully matched unrelated donors (MUD) (''alternative donors'') has been introduced in the allogeneic SCT setting in recent years. To evaluate the feasibility of allogeneic SCT from alternative donors by using peripheral blood stem cells (PBSC) we initiated a prospective, phase II study in 1996. From April 1996 to July 1998, 18 patients with various hematological malignancies underwent allogeneic SCT from alternative donors (two patients with MUD and 16 patients with MMRD). All patients received stable engraftment and none of the patients had graft rejection. The rate of aGvHD (grades II-IV) and the relapse rate at last follow-up (seven to nine yr after SCT) were with 40% and 24%, respectively, comparable with those found in patients receiving allogeneic SCT from MRD. However, five yr after allogeneic SCT only 17% were alive, which was mainly due to the treatment-related mortality (TRM) rate of 59%. We conclude that allogeneic PBSC transplantation by using alternative donors is associated with an unsatisfying long-term TRM rate. The significance of TRM and particular late deaths has to be evaluated further in this transplantation setting.


Subject(s)
Leukemia/therapy , Stem Cell Transplantation , Tissue Donors , Antigens, CD/blood , Family , Female , Filgrastim , Follow-Up Studies , Granulocyte Colony-Stimulating Factor/therapeutic use , Histocompatibility Testing , Humans , Leukemia/mortality , Male , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/therapy , Recombinant Proteins , Survival Analysis , Time Factors , Transplantation, Homologous
7.
Bone Marrow Transplant ; 39(7): 389-96, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17310135

ABSTRACT

In recent years, reduced-intensity conditioning (RIC) regimens before allogeneic stem cell transplantation (SCT) are increasingly used in patients not eligible for conventional conditioning. We did a retrospective, multicenter analysis to assess the feasibility of conditioning with fludarabine and treosulfan before allogeneic SCT in multiple myeloma patients. Thirty-four patients with a median age of 51.5 years were included in the analysis. All patients underwent myeloablation after conditioning followed by stable engraftment, and 29 of 31 evaluable patients (94%) showed early complete hematopoietic chimerism. Non-hematological toxicities were limited and encompassed mainly fever in neutropenia and infections. Grade II-IV acute and chronic graft-versus-host disease was observed in 33 and 39%, respectively. With a median follow-up of 708 days (range 60-1729 days), the median progression-free survival was 180 days. The treatment-related mortality was 10% on day 100 and 25% after 1 year. The median overall survival has not yet been reached. Our data indicate that conditioning with fludarabine and treosulfan before allogeneic SCT is feasible in intensively pretreated multiple myeloma patients and leads to stable engraftment and complete hematopoietic chimerism. Randomized trials are warranted to determine if this approach might be incorporated in an algorithm of multiple myeloma treatment.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents/therapeutic use , Busulfan/analogs & derivatives , Multiple Myeloma/therapy , Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Transplantation, Homologous/methods , Vidarabine/analogs & derivatives , Adult , Aged , Busulfan/therapeutic use , Disease-Free Survival , Female , Graft vs Host Disease , Humans , Male , Middle Aged , Retrospective Studies , Vidarabine/therapeutic use
9.
Leukemia ; 19(12): 2304-12, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16193083

ABSTRACT

Results of reduced intensity conditioning regimen (RIC) in the HLA identical haematopoietic stem cell transplantation (HSCT) setting have not been compared to those after myeloablative (MA) regimen HSCT in patients with acute myeloblastic leukaemia (AML) over 50 years of age. With this aim, outcomes of 315 RIC were compared with 407 MA HSCT recipients. The majority of RIC was fludarabine-based regimen associated to busulphan (BU) (53%) or low-dose total body irradiation (24%). Multivariate analyses of outcomes were used adjusting for differences between both groups. The median follow-up was 13 months. Cytogenetics, FAB classification, WBC count at diagnosis and status of the disease at transplant were not statistically different between the two groups. However, RIC patients were older, transplanted more recently, and more frequently with peripheral blood allogeneic stem cells as compared to MA recipients. In multivariate analysis, acute GVHD (II-IV) and transplant-related mortality were significantly decreased (P=0.01 and P<10(-4), respectively) and relapse incidence was significantly higher (P=0.003) after RIC transplantation. Leukaemia-free survival was not statistically different between the two groups. These results may set the grounds for prospective trials comparing RIC with other strategies of treatment in elderly AML.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/therapy , Transplantation Conditioning/methods , Aged , Cause of Death , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Female , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/mortality , Histocompatibility Testing , Humans , Male , Middle Aged , Multivariate Analysis , Recurrence , Registries , Retrospective Studies , Siblings , Survival Analysis , Transplantation, Homologous , Treatment Outcome
11.
Bone Marrow Transplant ; 35(10): 1011-8, 2005 May.
Article in English | MEDLINE | ID: mdl-15821768

ABSTRACT

A total of 155 patients with acute myeloid leukemia (AML) received hematopoietic stem cell transplants from unrelated donors after standard conditioning. Clinical outcome after the use of two different antithymocyte globulins for the prevention of graft-versus-host disease (GvHD) was analyzed in a retrospective study as follows: rabbit ATG (Thymoglobulin Sangstat/Genzyme, n=49, median age 42 years, 53% in CR, further ATG-S); rabbit ATG (ATG-Fresenius, n=38, median age 42 years, 58% in CR, further ATG-F) or no ATG (n=68, median age 36 years, 55% in CR). The groups were comparable regarding disease status at transplant, age, CMV status and cytogenetics. Grade III-IV acute GvHD was found in 15% in the ATG and 27% in the no ATG group (P=0.44). The most important independent risk factors for chronic GvHD (cGvHD) were the use of ATG, disease status at transplant and conditioning. cGvHD developed significantly more frequently in no ATG group. With the median follow-up of 34 months, the 5-year survival is 42% for those transplanted in CR. To conclude, these data demonstrate that the transplants performed in CR, with ATG, are associated with a good outcome, low incidence of cGvHD and no increase of relapse.


Subject(s)
Antilymphocyte Serum/therapeutic use , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/therapy , Adolescent , Adult , Antilymphocyte Serum/adverse effects , Female , Humans , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Multivariate Analysis , Recurrence , Retrospective Studies
12.
Bone Marrow Transplant ; 35(3): 233-41, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15592494

ABSTRACT

Treosulphan has recently demonstrated antileukaemic activity and potent haematopoietic stem cell toxicity. Dose-escalated treosulphan (3 x 12 or 3 x 14 g/m2) combined with cyclophosphamide (Cy) was chosen for a new preparative regimen before allogeneic haematopoietic stem cell transplantation in 18 patients (median age 44, range 19-64 years) with haematological malignancies, considered ineligible for other myeloablative preparative regimens. Pharmacokinetic studies demonstrated rapid treosulphan plasma clearance and a dose-dependent increase of its maximum plasma concentrations and area under the concentration-time curves. Rapid and sustained white blood cell and platelet recovery and full donor chimerism was attained in all evaluable patients. Nonhaematological regimen-related CTC grades 3-4 adverse events were transient and predominantly consisted of cardiac (28%), gastrointestinal (39%), and hepatic (39%) toxicities. The 1-year nonrelapse mortality was 22%. Principal causes of transplant-related lethal events were infections in three of four affected patients. Only one patient died from regimen-related cardiac toxicity. The 1-year relapse estimate is 22%, overall and progression-free survival estimates are 67 and 56%, respectively. In conclusion, this new treosulphan and Cy combination is an effective, comparatively well-tolerated myeloablative preparative regimen even in patients with an increased risk for regimen-related toxic complications.


Subject(s)
Busulfan/analogs & derivatives , Busulfan/administration & dosage , Cyclophosphamide/administration & dosage , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Adult , Aged , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/toxicity , Busulfan/pharmacokinetics , Busulfan/toxicity , Cause of Death , Dose-Response Relationship, Drug , Female , Graft Survival , Hematologic Neoplasms/complications , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , Male , Middle Aged , Pharmacokinetics , Recurrence , Risk Assessment , Survival Analysis , Transplantation Conditioning/adverse effects , Transplantation Conditioning/mortality , Transplantation, Homologous
13.
Leuk Lymphoma ; 46(2): 285-8, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15621815

ABSTRACT

We describe successful treatment of a 38-year-old patient with composite lymphoma stage IV(A), who presented with multifocal enlarged lymph nodes. The lymph node histology showed classic morphologic features of Hodgkin's disease, mixed cellularity subtype and follicular B-cell lymphoma. Immunophenotypic analysis showed immunoreactivity for CD20, CD10 and Ki-67 in the malignant small cell population. The areas of Hodgkin's disease demonstrated positive immunoreactivity for CD30 and CD20 in the Hodgkin's cells. Both cell populations were bcl2-oncoprotein positive. Eight courses of dose-escalated BEACOPP were administered. Restaging after chemotherapy showed radiological partial remission, but biopsy confirmed persisting follicular B-cell lymphoma without bone marrow infiltration and no evidence of Hodgkin's disease. He was treated with monoclonal CD 20-antibody (Rituximab) 10 mg/kg weekly for eight consecutive weeks due to marked positivity of CD 20-antigen in follicular lymphoma cells. This treatment was well tolerated and final staging showed complete remission of the composite lymphoma. This patient continues to be in remission 28 months after the end of the treatment. In conclusion, in the very rare case of composite lymphoma a combination of chemotherapy and subsequent immunotherapy might be considered as a promising therapeutic option.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma/drug therapy , Adult , Antibodies, Monoclonal, Murine-Derived , Antigens, CD20 , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Humans , Ki-67 Antigen , Leukemia, Lymphoid/drug therapy , Leukemia, Lymphoid/pathology , Lymphoma/pathology , Male , Neprilysin , Remission Induction/methods , Rituximab
14.
Bone Marrow Transplant ; 33(5): 483-90, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14716342

ABSTRACT

It is unknown whether the addition of antithymocyte globulin (ATG) to reduced-intensity conditioning with busulfan (BU) and fludarabine (FLU) is beneficial in HLA-identical sibling transplantation. Therefore, we analyzed retrospectively data on 83 patients, who received peripheral blood stem cells from HLA-identical siblings after conditioning with either 8 mg/kg BU and 150 mg/m2 FLU (n=45) or 8 mg/kg BU, 180 mg/m2 FLU and 40 mg/kg ATG (n=38). Graft-versus-host disease (GVHD) prophylaxis consisted of CSA alone (n=32) or a combination with either MTX or MMF (n=51). The median age was 52 years. Graft failure occurred in two patients after BU/FLU and in three after BU/FLU/ATG (P=0.66). After conditioning with BU/FLU, platelet recovery was significantly faster (P=0.017), and less platelet (P<0.001) and red blood cell (P=0.002) support was needed. Incidences of acute GVHD grades II and IV were 46 and 49%, respectively. Limited chronic GVHD occurred more often after BU/FLU compared to BU/FLU/ATG (54 vs 23%, P=0.02). The overall survival, non-relapse and relapse mortality did not differ significantly. We conclude that in peripheral blood stem cell transplantation from HLA-identical siblings after reduced-intensity conditioning with BU and FLU, ATG has no major impact on the rate of graft rejection and acute GVHD, but it reduces the incidence of limited chronic GVHD.


Subject(s)
Antilymphocyte Serum/administration & dosage , Busulfan/administration & dosage , Hematologic Neoplasms/drug therapy , Hematopoietic Stem Cell Transplantation , Immunosuppressive Agents/administration & dosage , Transplantation Conditioning/methods , Vidarabine/analogs & derivatives , Vidarabine/administration & dosage , Acute Disease , Adult , Aged , Chronic Disease , Combined Modality Therapy , Female , Follow-Up Studies , Graft vs Host Disease/mortality , Hematologic Neoplasms/mortality , Hematopoiesis , Histocompatibility Testing , Humans , Incidence , Male , Middle Aged , Recurrence , Retrospective Studies , Siblings , Survival Analysis , Transplantation, Homologous , Treatment Failure
15.
Bone Marrow Transplant ; 32(4): 355-61, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12900771

ABSTRACT

Matched unrelated donor transplants have an increased risk of severe graft-versus-host disease and transplant-related mortality (TRM). ATG has been introduced to decrease GvHD and to facilitate engraftment. We conducted a retrospective analysis of 333 patients with chronic myelogenous leukemia, who were treated with Fresenius ATG (n=145, average=90 mg/kg bw, range 40-90 mg/kg bw) or standard immunosuppression without ATG (n=188). Both groups were comparable regarding distribution of age, sex, HLA-matched vs mismatched donors. ATG Fresenius led to a faster leukocyte engraftment, decreased the incidence of acute GvHD and TRM (P=0.01 and P=0.03) and led to a significant better overall survival (70 vs 57%, P=0.03). We concluded that a prospective randomized study is needed to evaluate the definite role of ATG in hemopoietic stem cell transplantation.


Subject(s)
Antilymphocyte Serum/pharmacology , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Transplantation Conditioning/methods , Acute Disease , Adolescent , Adult , Child , Chronic Disease , Female , Humans , Immunophenotyping , Immunosuppressive Agents/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Leukocytes/metabolism , Male , Middle Aged , Multivariate Analysis , Recurrence , Retrospective Studies , Time Factors
16.
J Clin Oncol ; 21(14): 2747-53, 2003 Jul 15.
Article in English | MEDLINE | ID: mdl-12860954

ABSTRACT

PURPOSE: To study whether hematopoietic stem-cell transplantation (HSCT) after reduced-intensity conditioning is effective and tolerable in patients with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Thirty patients with advanced B-cell CLL were included into the study. After reduced-intensity conditioning with fludarabine, busulfan, and antithymocyte globulin, patients received a transplant from related (n = 15) or unrelated donors (n = 15). Minimal residual disease (MRD) was monitored with a clone-specific polymerase chain reaction. RESULTS: After a median follow-up of 2 years, 23 patients are alive (to date). Neutrophil and platelet engraftment occurred after a median of 17.5 and 15 days, respectively. Acute graft-versus-host disease (GVHD) grade 2 to 4 was observed in 17 patients (56%), and chronic GVHD was observed in 21 patients (75%). Twelve patients (40%) achieved a complete remission (CR), and 16 patients (53%) achieved a partial remission. Late CR occurred up to 2 years after transplantation. MRD was monitored in eight patients with CR. All patients achieved a molecular CR. At last follow-up, six patients were in ongoing molecular CR. Causes of death were treatment-related complications in four patients and progressive disease in three patients. The probability of overall survival, progression-free survival, and nonrelapse mortality at 2 years was 72% (95% confidence interval [CI], 54% to 90%), 67% (95% CI, 49% to 85%), and 15% (95% CI, 1% to 29%), respectively. CONCLUSION: Treatment-related mortality after reduced-intensity conditioning followed by allogeneic HSCT was low. The procedure induced molecular remissions in patients with advanced CLL. The observation of late remissions provided evidence of a graft-versus-leukemia effect.


Subject(s)
Busulfan/therapeutic use , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Transplantation Conditioning/methods , Vidarabine/analogs & derivatives , Vidarabine/therapeutic use , Adult , Aged , Child , Cohort Studies , Disease-Free Survival , Female , Follow-Up Studies , Graft Rejection , Graft Survival , Hematopoietic Stem Cell Transplantation/methods , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Male , Middle Aged , Probability , Retrospective Studies , Risk Assessment , Severity of Illness Index , Statistics, Nonparametric , Survival Rate , Transplantation, Homologous , Treatment Outcome
17.
Bone Marrow Transplant ; 31(12): 1089-95, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12796788

ABSTRACT

We analyzed predictive factors for the outcome of 113 acute myeloid leukemia patients receiving reduced-intensity conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT). Patients were ineligible for conventional-intensity HSCT. Conditioning consisted of fludarabine and 50% of the conventional dose of busulfan (n=93) or total body irradiation (n=20). The source of stem cells was blood in 102 patients, marrow in 10, and both in one. In total, 50 (44.2%) donors were HLA-matched siblings, 50 (44.2%) unrelated fully matched and 13 (11.5%) partially mismatched family (n=1) or unrelated (n=12) donors. In all, 107 (94.6%) patients showed neutrophil and platelet engraftment after a median time of 13.5 and 13 days. The probabilities of event-free survival (EFS) (median follow-up: 12 months) were 49% for patients with less than 5% blasts in the marrow, 24% for patients with 5-20% blasts (P=0.002) and 14% with >20% blasts (P

Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Transplantation Conditioning/methods , Adolescent , Adult , Aged , Female , Germany/epidemiology , Graft Survival , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Transplantation Conditioning/adverse effects , Transplantation, Homologous
18.
Bone Marrow Transplant ; 31(10): 935-7, 2003 May.
Article in English | MEDLINE | ID: mdl-12748673

ABSTRACT

We report a 30-year-old patient with therapy-refractory T-ALL undergoing unrelated allogeneic PBSCT. He developed severe tumor lysis syndrome (TLS) with extreme biochemical changes, cardiac and neurological symptoms and dialysis-dependent acute renal failure after TBI (4 Gy) on the first day of reduced intensity conditioning (RIC) for unrelated allogeneic PBSCT. The patient's clinical condition was stabilized after beginning daily hemodialysis and treatment for disturbed electrolytes, metabolic acidosis and plasma coagulation, as well as reduction of uric acid by rasburicase. The conditioning therapy and the allogenic PBSCT were scheduled according to the preparative regimen. According to our knowledge, severe TLS induced by 4 Gy TBI has not been reported so far. Regimen-related toxicity using RIC regimen was mild, allowing 30-50% of the patients to have an entirely outpatient transplantation. However, we would like to point out that severe TLS could also complicate PBSCT using RIC regimens in patients with relatively radiation-sensitive malignancies and high tumor burden.


Subject(s)
Leukemia-Lymphoma, Adult T-Cell/therapy , Stem Cell Transplantation/methods , Transplantation Conditioning/adverse effects , Tumor Lysis Syndrome/diagnostic imaging , Whole-Body Irradiation/adverse effects , Adult , Humans , Male , Radionuclide Imaging , Transplantation, Homologous , Tumor Lysis Syndrome/therapy
19.
Bone Marrow Transplant ; 30(10): 651-9, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12420203

ABSTRACT

According to recent reports, fast engraftment with minimal transplant-related toxicity and mortality (TRT, TRM) can be achieved by using reduced-intensity preparative regimens in allogeneic hematopoietic stem cell transplantation (HSCT). We report our experience with related (39%) and unrelated (61%) HSCT in 44 high risk patients (AML, ALL, CML, CLL) receiving either busulfan/fludarabine or busulfane/fludarabine/ATG or TBI/fludarabine as reduced-intensity preparative regimens. Organ toxicity was minimal with mild mucositis and no major bleeding. Acute GVHD was recorded in 64% of the patients. Twenty-three patients achieved complete remission after transplantation, and complete chimerism was obtained in all patients with stable engraftment (35 patients). Twenty-nine patients died: 15 due to relapse/progression, 14 due to TRM. Survival with median follow-up of 18.5 months was significantly better in patients with matched related transplants compared to patients with other transplants. However, there was no difference between related and unrelated transplants with regard to engraftment, TRM and GVHD. In conclusion, our results in high-risk patients transplanted in CR or with smoldering leukemia from a related donor are encouraging, although a longer follow-up and a larger group of patients is needed in order to evaluate the role of different reduced-intensity preparative regimens in unrelated and related HSCT.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Vidarabine/analogs & derivatives , Adult , Aged , Antilymphocyte Serum/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/toxicity , Busulfan/administration & dosage , Combined Modality Therapy , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , Leukemia/complications , Leukemia/mortality , Leukemia/therapy , Male , Middle Aged , Retrospective Studies , Survival Analysis , Transplantation Conditioning/adverse effects , Transplantation Conditioning/mortality , Transplantation, Homologous , Treatment Outcome , Vidarabine/administration & dosage , Whole-Body Irradiation
20.
Leukemia ; 16(12): 2423-8, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12454748

ABSTRACT

The feasibility of nonmyeloablative stem cell transplantation (NST) was evaluated in 22 adults with high-risk ALL. 16/22 patients had advanced disease and 11/22 had Ph+ ALL. Eleven patients received NST as first stem cell transplantation (SCT). Eleven patients had relapses after allogeneic or autologous SCT and underwent a salvage NST. 18/22 patients (82%) engrafted after NST. 13/16 patients (81%) with active disease reached complete remission (CR). 11 of 13 patients developed GVHD. After first NST 10/11 patients (91%) engrafted. Six of seven patients with active disease reached CR. Three of five relapsing patients reached subsequent CR after donor lymphocyte infusions, termination of immunosuppression or imatinib. Three of 11 patients (27%) are alive in CR 5 to 30 months after NST. Eight of 11 patients have died, 3/8 from leukemia and 5/8 from transplant-related causes. After salvage NST, 8/11 patients (73%) engrafted. Seven of nine patients with active disease reached CR. Only one of 11 patients transplanted, who was in CR before undergoing salvage NST is alive 19 months after NST. Five of 11 have died from leukemia, one of 11 after graft failure and four of 11 from transplant-related causes. Four of 22 patients (18%) are alive in CR 5, 14, 19 and 30 months after NST. NST is feasible in adults with high risk ALL. However, transplant-related mortality remains high and only patients transplanted in CR seem to have long-term disease-free survival.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Transplantation Conditioning/methods , Adult , Combined Modality Therapy , Disease Progression , Feasibility Studies , Female , Graft vs Leukemia Effect , Humans , Male , Middle Aged , Philadelphia Chromosome , Pilot Projects , Remission Induction/methods , Risk , Salvage Therapy , Survival Analysis , Survival Rate , Transplantation Conditioning/adverse effects
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