Publications by authors named "Ana Sureda"

17 Publications

  • Page 1 of 1

Lower Graft-versus-Host Disease and Relapse Risk in Post-Transplant Cyclophosphamide-Based Haploidentical versus Matched Sibling Donor Reduced-Intensity Conditioning Transplant for Hodgkin Lymphoma.

Biol Blood Marrow Transplant 2019 09 25;25(9):1859-1868. Epub 2019 May 25.

Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address:

Classic Hodgkin lymphoma (cHL) patients with relapsed or refractory disease may benefit from allogeneic hematopoietic cell transplantation (allo-HCT), but many lack a matched sibling donor (MSD). Herein, we compare outcomes of 2 reduced-intensity conditioning (RIC) HCT platforms in cHL: T cell-replete related donor haploidentical (haplo) HCT with a post-transplant cyclophosphamide (PTCy)-based approach versus an MSD/calcineurin inhibitor (CNI)-based approach. The study included 596 adult patients who underwent a first RIC allo-HCT for cHL between 2008 and 2016 using either a haplo-PTCy (n = 139) or MSD/CNI-based (n = 457) approach. Overall survival (OS) was the primary endpoint. Secondary endpoints included acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). On multivariate analysis, there was no significant difference between haplo/PTCy and MDS/CNI-based approaches in terms of OS (hazard ratio [HR], 1.07; 95% confidence interval [CI], .79 to 1.45; P = .66) or PFS (HR, .86; 95% CI, .68 to 1.10; P = .22). Haplo/PTCy was associated with a significantly higher risk of grades II to IV aGVHD (odds ratio [OR], 1.73, 95% CI, 1.16 to 2.59; P = .007), but the risk of grades III to IV aGVHD was not significantly different between the 2 cohorts (OR, .61; 95% CI, .29 to 1.27; P = .19). The haplo/PTCy platform provided a significant reduction in cGVHD risk (HR, .45; 95% CI, .32 to .64; P < .001), and a significant reduction in relapse risk (HR, .74; 95% CI, .56 to .97; P = .03). There was a statistically nonsignificant trend toward higher NRM with a haplo/PTCy approach (HR, 1.65; 95% CI, .99 to 2.77; P = .06). Haplo/PTCy-based approaches are associated with lower incidences of cGVHD and relapse, with PFS and OS outcomes comparable with MSD/CNI-based approaches. There was a leaning toward higher NRM with a haplo/PTCy-based platform. These data show that haplo/PTCy allo-HCT in cHL results in survival comparable with MSD/CNI-based allo-HCT.
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http://dx.doi.org/10.1016/j.bbmt.2019.05.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755039PMC
September 2019

Allogeneic hematopoietic cell transplantation provides effective salvage despite refractory disease or failed prior autologous transplant in angioimmunoblastic T-cell lymphoma: a CIBMTR analysis.

J Hematol Oncol 2019 01 10;12(1). Epub 2019 Jan 10.

Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Suite C5500, 8701 W. Watertown Plank Rd, Milwaukee, WI, 53226, USA.

Background: There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT.

Methods: We evaluated 249 adult AITL patients who received their first allo-HCT during 2000-2016.

Results: The median patient age was 56 years (range = 21-77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 months (range = 4-170 months). The cumulative incidence of grade 2-4 and grade 3-4 acute GVHD at day 180 were 36% (95% CI = 30-42) and 12 (95% CI = 8-17), respectively. The cumulative incidence of chronic GVHD at 1 year was 49% (95%CI 43-56). The 1-year non-relapse mortality (NRM) was 19% (95% CI = 14-24), while the 4-year relapse/progression, progression-free survival (PFS), and overall survival (OS) were 21% (95% CI = 16-27), 49% (95% CI = 42-56), and 56% (95% CI = 49-63), respectively. On multivariate analysis, chemoresistant status at the time of allo-HCT was associated with a significantly higher risk for therapy failure (inverse of PFS) (RR = 1.73 95% CI = 1.08-2.77), while KPS < 90% was associated with a significantly higher risk of mortality (inverse of OS) (RR = 3.46 95% CI = 1.75-6.87).

Conclusion: Our analysis shows that allo-HCT provides durable disease control even in AITL patients who failed a prior auto-HCT and in those subjects with refractory disease at the time of allografting.
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http://dx.doi.org/10.1186/s13045-018-0696-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329157PMC
January 2019

Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial.

Lancet Oncol 2010 Oct 23;11(10):934-41. Epub 2010 Aug 23.

University Hospital of Salamanca, Salamanca, Spain.

Background: Bortezomib plus melphalan and prednisone (VMP) is significantly better than melphalan plus prednisone alone for elderly patients with untreated multiple myeloma; however, toxic effects are high. We investigated a novel and less intensive bortezomib-based regimen to maintain efficacy and to reduce toxic effects.

Methods: Between March, 2006, and October, 2008, 260 patients with untreated multiple myeloma, 65 years and older, from 63 Spanish centres, were randomly assigned to receive six cycles of VMP (n=130) or bortezomib plus thalidomide and prednisone (VTP; n=130) as induction therapy, consisting of one cycle of bortezomib twice per week for 6 weeks (1·3 mg/m² on days 1, 4, 8, 11, 22, 25, 29, and 32), plus either melphalan (9 mg/m² on days 1-4) or daily thalidomide (100 mg), and prednisone (60 mg/m² on days 1-4). The first cycle was followed by five cycles of bortezomib once per week for 5 weeks (1·3 mg/m² on days 1, 8, 15, and 22) plus the same doses of melphalan plus prednisone and thalidomide plus prednisone. 178 patients completed the six induction cycles and were randomly assigned to maintenance therapy with bortezomib plus prednisone (n=87) or bortezomib plus thalidomide (n=91), consisting of one conventional cycle of bortezomib for 3 weeks (1·3 mg/m² on days 1, 4, 8, and 11) every 3 months, plus either prednisone (50 mg every other day) or thalidomide (50 mg per day), for up to 3 years. Treatment codes were generated with a computerised random number generator, and neither participants nor study personnel were masked to treatment. The primary endpoint was response rate in induction and maintenance phases. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00443235.

Findings: In the induction phase, 105 (81%) patients in the VTP group and 104 (80%) in the VMP group achieved partial responses or better (p=0·9), including 36 (28%) and 26 (20%) complete remissions, respectively (p=0·2). Treatment with VTP resulted in more serious adverse events (40 [31%] vs 20 [15%], p=0·01) and discontinuations (22 [17%] vs 15 [12%], p=0·03) than did treatment with VMP. The most common toxicities (grade 3 or worse) were infections (one [1%] in the VTP group vs nine [7%] in the VMP group), cardiac events (11 [8%] vs 0), and peripheral neuropathy (nine [7%] vs 12 [9%]). After maintenance therapy, the complete remission rate was 42% (40 [44%] patients in complete remission in the bortezomib plus thalidomide group, 34 [39%] in the bortezomib plus prednisone group). No grade 3 or worse haematological toxicities were recorded during maintenance therapy; two (2%) patients in the bortezomib plus prednisone group and six (7%) in the bortezomib plus thalidomide group developed peripheral neuropathy.

Interpretation: Reduced-intensity induction with a bortezomib-based regimen, followed by maintenance, is a safe and effective treatment for elderly patients with multiple myeloma.

Funding: Pethema (Spanish Program for the Treatment of Hematologic Diseases).
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http://dx.doi.org/10.1016/S1470-2045(10)70187-XDOI Listing
October 2010

Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events results and prognostic factors for time to progression.

Haematologica 2008 Apr 5;93(4):560-5. Epub 2008 Mar 5.

Hospital Universitario de Salamanca, Salamanca, Spain.

Background: New treatment options offering enhanced activity in elderly, newly diagnosed patients with multiple myeloma are required. One strategy is to combine melphalan and prednisone with novel agents. We previously reported an 89% response rate, including 32% complete responses and 11% near complete responses, in our phase 1/2 study of bortezomib plus melphalan and prednisone (VMP) in 60 newly diagnosed multiple myeloma patients with a median age of 75 years. Here, we report updated time-to-events data and the impact of poor prognosis factors on outcome.

Design And Methods: Updated analyses of time to biochemical progression and overall survival with VMP were conducted, and compared with those of historical controls treated with melphalan and prednisone. A univariate analysis was performed to evaluate the influence of known prognostic factors on the time to progression.

Results: After a median follow-up of 26 months, the median time to progression with VMP was 27.2 months, compared with 20.0 months with melphalan plus prednisone. The median overall survival with VMP was not reached versus 26 months with melphalan and prednisone; the survival rate at 38 months was 85% versus 38%, respectively. Time to progression was not significantly affected by elevated beta(2)-microglobulin or lactate dehydrogenase levels, advanced age, or cytogenetic abnormalities, but was shorter in patients with albumin < 3 g/dL, Karnofsky performance status < or =70%, bone marrow plasma cell infiltration > or =40%, and, particularly, high plasma cell proliferative activity (> or = 2.5% S-phase cells).

Conclusions: VMP is highly active and well tolerated in elderly patients with newly diagnosed multiple myeloma, with 85% of patients alive at 3 years. Moreover, VMP may overcome the poor prognostic impact of various factors, particularly cytogenetic abnormalities.
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http://dx.doi.org/10.3324/haematol.12106DOI Listing
April 2008

Results of treatment with doxorubicin, bleomycin, vinblastine and dacarbazine and highly active antiretroviral therapy in advanced stage, human immunodeficiency virus-related Hodgkin's lymphoma.

Haematologica 2007 Feb;92(2):191-8

Institut Català d' Oncologia-Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

Background And Objectives: Although doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) is considered the standard chemotherapy regimen for Hodgkin's lymphoma (HL), information on the results of this therapy in human immunodeficiency (HIV)-related HL is scarce. We analyzed the results of the ABVD regimen and highly active antiretroviral therapy (HAART) in patients with advanced stage, HIV-related HL.

Design And Methods: From January 1996 to December 2005, 62 HIV-infected patients with newly diagnosed HL were treated in 15 Spanish hospitals. Six to eight cycles of ABVD and HAART were planned. Response to chemotherapy, overall survival (OS) and event-free survival (EFS) were recorded.

Results: The median age of the patients was 37 years (range, 24-61) and 29 (47%) had a previously known diagnosis of acquired immunodeficiency syndrome. The median CD4 lymphocyte count at diagnosis was 129/muL (range 5-1,209). The histologic subtype of HL was nodular sclerosis in 17 patients (27%), mixed cellularity in 25 (41%), lymphocyte depletion in 10 (16%) and non-specified in the remaining 10 (16%). Twenty-one (34%) patients were in stage III and 41 (66%) in stage IV. The scheduled six to eight ABVD cycles were completed in 82% of cases. Six patients died during induction, 54 (87%) achieved a complete response (CR) and two were resistant. After a median follow-up of 39 and 47 months, 5-year EFS and OS probabilities were 71% (47-95) and 76% (65-87), respectively. An immunological response was observed in 24 out of 43 patients (56%) and a virological response in 27 out of 40 (68%). The immunological response to HAART had a positive impact on OS and EFS (p=0.002 and p=0.001, respectively).

Interpretation And Conclusions: In patients with advanced stage, HIV-related HL, treatment with ABVD together with HAART is feasible and effective. This supports the concept that patients with HIV-related HL should be treated in the same way as immunocompetent patients if HAART, adequate supportive therapy and anti-infectious prophylaxis are given concomitantly. An immunological response to HAART has a positive impact on OS and EFS.
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http://dx.doi.org/10.3324/haematol.10479DOI Listing
February 2007

Membrane PKC-beta 2 protein expression predicts for poor response to chemotherapy and survival in patients with diffuse large B-cell lymphoma.

Ann Hematol 2006 Sep 8;85(9):597-603. Epub 2006 Jul 8.

Department of Pathology, Hospital de la Santa Creu i Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain.

The protein kinase C (PKC) plays an important role in the activation and survival of B cells. The purpose of this study was to analyze the clinical significance of PKC-beta 2 protein expression in patients with diffuse large B-cell lymphoma (DLBCL). Tumors from 76 patients with DLBCL who received anthracycline-containing chemotherapy were examined for PKC-beta 2 protein expression by immunohistochemistry. Twenty-six cases (34%) were positive for PKC-beta 2 protein, and 50 (66%) were negative. Patients with PKC-beta-2-positive tumors showed a lower complete remission rate (31 vs 62%; P=0.015) and a lower 5-year disease-free survival (DFS) (30 vs 60%; P=0.03) than the PKC-beta-2-negative group. Overall survival (OS) was significantly lower in patients with the membranous staining pattern of PKC-beta 2 protein when compared to those with PKC-beta-2-negative tumors (14 vs 64%; P=0.005). In patients with low international prognostic index (IPI), those with tumors showing membrane expression of PKC-beta 2 had a significantly inferior DFS and OS (0 vs 79%, P=0.003; 25 vs 80%; P=0.01) compared to PKC-beta-2-negative tumors. In multivariate analysis for OS, the membrane staining of PKC-beta 2 is the strongest independent adverse prognostic factor (OR=3.4, P=0.011). Our results suggest that membrane expression of PKC-beta 2 protein on DLBCL predicts for poor survival, especially in patients with low IPI.
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http://dx.doi.org/10.1007/s00277-006-0144-yDOI Listing
September 2006

Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study.

Blood 2006 Oct 13;108(7):2165-72. Epub 2006 Jun 13.

Hematology Division, Grupo Español de MM, Spain. Paseo San Vicente 58-182; 37007 Salamanca, Spain.

Standard first-line treatment for elderly multiple myeloma (MM) patients ineligible for stem cell transplantation is melphalan plus prednisone (MP). However, complete responses (CRs) are rare. Bortezomib is active in patients with relapsed MM, including elderly patients. This phase 1/2 trial in 60 untreated MM patients aged at least 65 years (half older than 75 years) was designed to determine dosing, safety, and efficacy of bortezomib plus MP (VMP). VMP response rate was 89%, including 32% immunofixation-negative CRs, of whom half of the IF- CR patients analyzed achieved immunophenotypic remission (no detectable plasma cells at 10(-4) to 10(-5) sensitivity). VMP appeared to overcome the poor prognosis conferred by retinoblastoma gene deletion and IgH translocations. Results compare favorably with our historical control data for MP--notably, response rate (89% versus 42%), event-free survival at 16 months (83% versus 51%), and survival at 16 months (90% versus 62%). Side effects were predictable and manageable; principal toxicities were hematologic, gastrointestinal, and peripheral neuropathy and were more evident during early cycles and in patients aged 75 years or more. In conclusion, in elderly patients ineligible for transplantation, the combination of bortezomib plus MP appears significantly superior to MP, producing very high CR rates, including immunophenotypic CRs, even in patients with poor prognostic features.
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http://dx.doi.org/10.1182/blood-2006-04-019778DOI Listing
October 2006

High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA.

Blood 2005 Dec 16;106(12):3755-9. Epub 2005 Aug 16.

Hematology Department, Hospital Clínic, IDIBAPS, Villarroel 170, 08036 Barcelona, Spain.

The aim of the present randomized trial was to compare high-dose therapy (HDT) with continued conventional chemotherapy in patients with multiple myeloma (MM) who responded to the initial treatment. From May 1994 to October 1999, 216 patients (122 men/94 women; stage II or III; Eastern Cooperative Oncology Group [ECOG] score less than 3) entered the study. Initial chemotherapy consisted of 4 cycles of alternating vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, Adriamycin, dexamethasone (VBMCP/VBAD). Responding patients were randomly assigned to receive 8 additional cycles of VBMCP/VBAD, intensification with melphalan 200 mg/m2, or melphalan 140 mg/m2 plus 12 Gy fractionated total body irradiation (TBI). One-hundred sixty-four patients were randomly assigned, 83 to continued chemotherapy and 81 to HDT. The complete remission (CR) rate was significantly higher with HDT (30% vs 11%; P = .002). However, progression-free survival (PFS) was not significantly different between HDT and conventional therapy (median, 42 vs 33 months; P = not significant [NS]), and overall survival (OS) was similar in both groups (median, 61 vs 66 months). Finally, survival after relapse was identical in the 2 arms (15.9 vs 16.4 months). In conclusion, these results show that HDT intensification, when given to myeloma patients who have responded to the initial chemotherapy, significantly increases the CR rate but has no significant impact on PFS or OS.
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http://dx.doi.org/10.1182/blood-2005-03-1301DOI Listing
December 2005

Erythropoietin treatment of the anaemia of myelofibrosis with myeloid metaplasia: results in 20 patients and review of the literature.

Br J Haematol 2004 Nov;127(4):399-403

Haematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.

Recombinant human erythropoietin (rHuEPO) is an effective treatment for the anaemia that occurs secondary to various conditions, but its role in myelofibrosis with myeloid metaplasia (MMM) is not well established. rHuEPO, at an initial dose of 10 000 U thrice a week, was given to 20 patients with MMM and anaemia. Complete response (CR) was defined as transfusion cessation with normal haemoglobin (Hb) levels and partial response (PR) as a transfusion decrease > or =50% and Hb > 10 g/dl maintained for at least 8 weeks. Nine patients (45%) showed a favourable response to treatment, including four CR and five PR, four of whom have maintained their response at a median follow-up of 12.5 months (range: 4-21 months) from the start of treatment. The pretreatment factors associated with a favourable response were lack of transfusion requirement (P = 0.002) and higher Hb at start treatment of (P = 0.01). An analysis of the present series (n = 20) and 31 patients from the literature identified 28 (55%) favourable responses to rHuEPO, including 16 CR and 12 PR. In the multivariate analysis, serum erythropoietin level <125 U/l was found to be associated with a favourable response to rHuEPO, whereas lack of transfusional support had borderline significance.
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http://dx.doi.org/10.1111/j.1365-2141.2004.05229.xDOI Listing
November 2004

Strategies to reduce transplant-related mortality after allogeneic stem cell transplantation in elderly patients: Comparison of reduced-intensity conditioning and unmanipulated peripheral blood stem cells vs a myeloablative regimen and CD34+ cell selection.

Exp Hematol 2003 Nov;31(11):1039-43

Clinical Hematology Division, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Objectives: The aim of this study was to compare two approaches used to reduce transplant-related mortality (TRM) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in elderly patients.

Patients And Methods: Data from 50 patients, 45 years of age or older, consecutively treated with an HLA-identical sibling allo-PBSCT at the Hospital de Sant Pau were analyzed. We have compared the outcome of patients treated with conventional myeloablative regimens and CD34(+)-selected cells (CD34(+) group; n=23) with those receiving reduced-intensity conditioning regimens, consisting of fludarabine (150 mg/m(2)) plus an alkylating agent, followed by unmanipulated grafts (RIC group; n=27). Patient characteristics were well balanced between the two groups, although patients in the RIC group were slightly older.

Results: The incidence of acute graft-vs-host disease (GVHD) was similar in both groups. The 1-year cumulative incidence of extensive chronic GVHD was 38% in the RIC group and 17% in the CD34(+) group (p=0.2). After a median follow-up of 28 months, there were no differences in the relapse rate. Patients in the RIC group had a lower TRM, with a cumulative incidence of 7% vs 30% at 6 months and 15% vs 39% at 1 year (p=0.05). The Kaplan-Meier estimates of PFS at 2 years was 67% in the RIC group and 43% in the CD34(+) group (p=0.09) and the OS was 69% vs 43% (p=0.05), respectively.

Conclusion: CD34(+) cell selection reduced the risk of extensive cGVHD but was associated with a higher TRM. Although the number of patients is limited, our study suggests that this approach should be restricted to relatively young patients, as better outcomes can be achieved in elderly patients using RIC strategies.
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http://dx.doi.org/10.1016/s0301-472x(03)00223-6DOI Listing
November 2003

Chronic but not acute graft-versus-host disease improves outcome in multiple myeloma patients after non-myeloablative allogeneic transplantation.

Br J Haematol 2003 Apr;121(1):104-8

Hospital Clínico Universitario, Salamanca, Spain.

The outcome of 29 multiple myeloma patients receiving fludarabine and melphalan-based non-myeloablative allogeneic transplant (NMT) was evaluated. Event-free survival (EFS) at 24 months was 33%, being significantly higher for patients who developed chronic graft-versus-host disease (cGVHD) when compared with those who did not [51%vs 0% respectively, P = 0.02; hazard rate = 3.16 (95% confidence interval = 1.09-9.15, P = 0.03)] as well as for patients transplanted in complete remission/partial response (CR/PR) or stable disease (SD), compared with those with refractory/progressive disease (43%vs 0% respectively, P = 0.02). Overall survival (OS) at 24 months was 60%[72%vs 42% for patients who did and did not develop cGVHD respectively (P = 0.1); 63%vs 41% for patients in CR/PR or SD vs refractory/progressive disease at transplant respectively (P = 0.013)]. At a median follow-up of 366 d, 13 patients remained in CR/PR (45% overall response rate). Nine patients have died, three of them as a result of disease progression and six (21%) as a result of transplant-related mortality (TRM). Actuarial incidence of TRM was 37% for patients who developed acute GVHD vs 13% for those who did not (log rank, P = 0.04). The present study suggests that graft-versus-myeloma effect is the main weapon for disease control after NMT in MM patients and the efficacy of this immune effect depends on tumour burden before transplant.
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http://dx.doi.org/10.1046/j.1365-2141.2003.04237.xDOI Listing
April 2003

Combined treatment with anti-CD20 (rituximab) and CHOP in relapsed advanced-stage follicular lymphomas.

Haematologica 2002 Nov;87(11):1229-30

We studied the safety and efficacy of combined treatment with rituximab plus CHOP in 16 patients with relapsed advanced-stage follicular lymphomas. The intent-to-treat overall response rate (ORR) was 88%, 75% complete remissions (CR) and 13% partial remissions (PR). At a median follow-up of 18 months, 63% of the patients are alive (50% CR). The combination of rituximab and CHOP in relapsed advanced-stage follicular lymphomas achieves high ORRs and CRs, with low toxicity except for in previously autografted patients.
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November 2002

Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders.

Blood 2002 Nov;100(9):3121-7

Department of Hematology, Hospital Universitairo de Salamanca, Paseo de San Vicente s/n, 37007 Salamanca, Spain.

Although nonmyeloablative conditioning regimen transplantations (NMTs) induce engraftment of allogeneic stem cells with a low spectrum of toxicity, graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality. In vivo T-cell depletion, using alemtuzumab, has been shown to reduce the incidence of GVHD. However, this type of maneuver, although reducing GVHD, may have an adverse impact on disease response, because NMTs exhibit their antitumor activity by relying on a graft-versus-malignancy effect. To explore the efficacy of alemtuzumab compared with methotrexate (MTX) for GVHD prophylaxis, we have compared the results in 129 recipients of a sibling NMT enrolled in 2 prospective studies for chronic lymphoproliferative disorders. Both NMTs were based on the same combination of fludarabine and melphalan, but the United Kingdom regimen (group A) used cyclosporin A plus alemtuzumab, whereas the Spanish regimen (group B) used cyclosporin A plus MTX for GVHD prophylaxis. Patients receiving alemtuzumab had a higher incidence of cytomegalovirus (CMV) reactivation (85% versus 24%, P <.001) and a significantly lower incidence of acute GVHD (21.7% versus 45.1%, P =.006) and chronic GVHD (5% versus 66.7%, P <.001). Twenty-one percent of patients in group A and 67.5% in group B had complete or partial responses 3 months after transplantation (P <.001). Eighteen patients in group A received donor lymphocyte infusions (DLIs) to achieve disease control. At last follow-up there was no difference in disease status between the groups with 71% versus 67.5% (P =.43) of patients showing complete or partial responses in groups A and B, respectively. No significant differences were observed in event-free or overall survival between the 2 groups. In conclusion, alemtuzumab significantly reduced GVHD but its use was associated with a higher incidence of CMV reactivation. Patients receiving alemtuzumab often required DLIs to achieve similar tumor control but the incidence of GVHD was not significantly increased after DLI.
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http://dx.doi.org/10.1182/blood-2002-03-0701DOI Listing
November 2002

The post-transplant cytogenetic response to interferon is a major determinant of survival after autologous stem cell transplantation for chronic myeloid leukaemia in chronic phase.

Br J Haematol 2002 Sep;118(3):762-70

Haematology Department, Hammersmith Hospital, ICSM, London, UK.

We have analysed the outcome of 581 autologous stem cell transplants (SCT) for chronic myeloid leukaemia (CML) in first chronic phase reported to the European Group for Blood and Marrow Transplantation between 1983 and 1998. Out off 207 patients evaluable for cytogenetics within 6 months of SCT, 36 patients (17%) were in complete cytogenetic remission (CCR), 34 (16%) in major remission (MCR), 74 (36%) in minor remission (mCR) and 63 (31%) had no cytogenetic response (NR). Interferon (IFN) was given post SCT to 267 patients. Results of the cytogenetic analysis within 1-2 years from SCT were available for 117 patients, the majority of whom (n = 101) received IFN post SCT: 17 (15%) were in CCR, 18 (15%) in MCR, 24 (20%) in mCR and 58 (50%) NR. The median survival in this series was 96 months (71-125) from SCT. There was no difference in survival according to cytogenetic status pre- and immediately post SCT. However, patients in CCR or MCR at 1-2 years post SCT had a 10-year survival of 66% compared with 36% for patients in mCR or NR (P = 0.003). The 5-year survival for patients receiving IFN post SCT was 72% compared with 61% for patients not treated with IFN (P = 0.01). Out of 155 patients refractory to IFN pre SCT, 70% achieved a cytogenetic response post SCT, which was complete or major in 31%. IFN refractory patients who sustained a CCR or MCR for 1-2 years after SCT had an excellent outcome.
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http://dx.doi.org/10.1046/j.1365-2141.2002.03600.xDOI Listing
September 2002

Invasive pulmonary aspergillosis in patients with hematologic malignancies: survival and prognostic factors.

Haematologica 2002 May;87(5):528-34

Servei d'Hematologia Clinica, Hospital de la Santa Creu i Sant Pau, Av. S.A.M. Claret 167, 08025 Barcelona, Spain.

Background And Objectives: Despite improvements made in its early diagnosis and effective treatment, invasive pulmonary aspergillosis (IPA) remains a devastating opportunistic infection. In this retrospective study we have reviewed all consecutive cases of IPA diagnosed in adult patients with hematologic malignancies in our center from 1995 to 2000 to determine survival and prognostic factors.

Design And Methods: Forty-one patients were included in the study. Ante-mortem classification of cases of IPA were: 4 definite, 10 highly probable, 19 probable and 8 possible cases; all these last eight patients were later upgraded to definite IPA at post-mortem examination. Clinical charts were reviewed and factors possibly affecting the outcome of IPA were analyzed.

Results: All but two patients received chemotherapy and/or immunosuppresive therapy before the onset of IPA (conventional chemotherapy = 24, allogeneic stem cell transplantation [SCT] = 12, autologous SCT = 3). At IPA diagnosis 28 patients were neutropenic (< 0.5 x 10(9)/L) for a median of 25 days (range 7-135), and 10 allogeneic SCT patients were receiving corticosteroids for graft-versus-host-disease. All but two patients received antifungal treatment for IPA. The median delay from diagnosis to start of therapy was two days (range 0-20). The median follow-up after the first symptom or sign of IPA was 42 days with a maximum follow-up of 61 months. The actuarial 4-month infection-free survival was 40% (95% CI 25% to 55%). Thirty-three patients died during follow-up and IPA was implicated in the patients' death in 24 cases (75%). In multivariate analysis prolonged survival was associated with recovery of neutropenia during treatment (p = 0.001) and not having received an allogeneic SCT (p = 0.003).

Interpretation And Conclusions: Despite prompt initiation of antifungal therapy, survival of patients with a hematologic malignancy and IPA is currently low. Perhaps the introduction of more sensitive diagnostic methods will allow the onset of intensive therapy prior to the appearance of more advanced clinical symptoms and/or radiological signs, and the time will come to test whether earlier and more intensive therapy will improve survival.
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May 2002