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S Giralt

Publications and source records attributed to S Giralt.

At least 19 recordsLinked to original sources
PubMed2006

Phase II study of unrelated cord blood transplantation for adults with high-risk hematologic malignancies.

Cell dose is a critical determinant of outcomes in unrelated cord blood (CB) transplantation. We investigated a strategy in which CB units should contain at least 2 x 10(7) total nucleated cells/kg of recipient weight, otherwise a second unit had to be added. We report the results of a study that was prematurely closed owing to toxicity. Patients with advanced hematologic malignancies without a human leukocyte antigen-matched sibling or unrelated donor were eligible. Conditioning regimen consisted of fludarabine and 12 Gy of total body irradiation (n=11), or melphalan (n=4), with antithymocyte globulin. Graft-versus-host disease prophylaxis was tacrolimus and methotrexate. Fifteen patients with acute leukemia (n=9), chronic myelogenous leukemia (n=2), multiple myeloma (n=2) and lymphoma (n=2) were treated; 60% had relapsed disease at transplantation. Three patients received double CB transplants. The 100-day and 1-year treatment-related mortality rates were 40 and 53%, respectively. Median time to neutrophil and platelet engraftment was 22 days (n=10) and 37 days (n=10), respectively. One patient had secondary graft failure and five patients failed to engraft. Two patients are alive and disease free; 4-year actuarial survival is 33 versus 0% for patients transplanted in remission versus in relapse. We concluded that disease status was the main determinant of treatment failure in this study.

Adult↗
PubMed2006

Steroid myopathy in patients with acute graft-versus-host disease treated with high-dose steroid therapy.

High-dose steroids are the first line of treatment for acute graft-versus-host disease (aGVHD). Steroid myopathy is a debilitating steroid-induced complication that significantly impairs a patient's performance status. To determine the frequency and severity of steroid myopathy and other steroid related complications in patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) who developed grade >or=2 aGVHD after allogeneic hematopoietic stem cell transplantation (HSCT), we performed a retrospective analysis. Patients were included in the analysis if they had a diagnosis of AML/MDS, underwent an allogeneic HSCT between January 1996 and December 2001 and developed grade >or=2 aGVHD that was treated with 2 mg/kg of methylprednisolone and survived at least 100 days post transplant. A total of 70 patients fulfilled our inclusion criteria. Steroid myopathy was identified in 29 (41%) patients. Steroid myopathy was generally of moderate severity with severe debilitating steroid myopathy seen in only 3% of patients. We concluded that steroid myopathy is a common complication of high-dose steroid therapy after allogeneic HSCT in AML/MDS. Interventions aimed at preventing and treating this complication are warranted and need to be explored in prospective clinical trials.

Acute Disease↗
PubMed2006

Allogeneic hematopoietic stem cell transplantation after rituximab-containing myeloablative preparative regimen for acute lymphoblastic leukemia.

We explored the safety and efficacy of rituximab administered in combination with the standard transplant conditioning regimen of cyclophosphamide (Cy) 120 mg/kg and total body irradiation (TBI) 12 Gy for adult patients with acute lymphoblastic leukemia (ALL). Patients were eligible if their disease expressed CD20. Rituximab was administered at 375 mg/m2 weekly for four doses beginning on day -7 of the conditioning regimen. Graft-versus-host-disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Thirty-five patients undergoing matched sibling (n = 23) or unrelated donor (n = 12) transplantation were studied, with a median age of 30 years (range 15-55 years). At 2 years, progression-free survival, treatment-related mortality, and overall survival were 30, 24, and 47%, respectively. There was no delay in engraftment or increased incidence of infection. The cumulative incidence of grade II-IV acute GVHD was 17%, and limited and extensive chronic GVHD was 43% at 2 years. The addition of rituximab to the standard Cy/TBI transplant conditioning regimen in ALL was safe and well tolerated, and there was a suggestion of decreased incidence of acute GVHD when compared to historically reported GVHD rates for this group of patients.

Adolescent↗
PubMed2005

Outcome of unrelated transplants in patients with multiple myeloma.

The outcome of patients with multiple myeloma treated with standard therapy is disappointing, with a historical median survival of 3 years. Although high-dose therapy with autologous stem cell transplant has improved treatment outcomes, cure is unlikely. Allogeneic transplant provides a tumor-free graft and a graft-versus-myeloma effect. However, only a minority of patients has a compatible sibling donor. Unrelated hematopoietic stem cell transplant is another option. We analyzed the outcome of patients who received an unrelated bone marrow transplant facilitated by the National Marrow Donor Program (NMDP). Between 1989 and 2000, 71 patients received a myeloablative unrelated transplant for multiple myeloma; 70 patients consented for this analysis. The median recipient age was 44 years. A total of 31% of patients had received a prior autologous transplant. In all, 91% of patients engrafted. The 3-year cumulative incidence estimate of relapse was 34+/-10%. The incidence of Grade II-IV GVHD was 47%. The Kaplan-Meier estimate for overall survival at 5 years was 9+/-7%. The 100-day treatment-related mortality was 42%. In multivariate analysis, only a male donor was a significant predictor for survival. Better strategies are needed to treat patients with multiple myeloma, perhaps by using less-toxic, nonmyeloablative conditioning regimens.

Adult↗
PubMed2005

Reduced-intensity allogeneic stem cell transplantation in relapsed and refractory Hodgkin's disease: low transplant-related mortality and impact of intensity of conditioning regimen.

A total of 40 patients with relapsed/refractory Hodgkin's disease (HD) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) from an HLA-identical sibling (n=20) or a matched unrelated donor (n=20). The median age was 31 years (range 18-58). Disease status at allo-SCT was refractory relapse (n=14) or sensitive relapse (n=26). The conditioning regimens were fludarabine-cyclophosphamide+/-antithymocyte globulin (n=14), a less intensive regimen, and fludarabine-melphalan (FM) (n=26), a more intensive one. The two groups had similar prognostic factors. The median time to neutrophil recovery (ie absolute neutrophil count >/=500/microl) was 12 days (range 10-24). The median time to platelet recovery (ie platelet count >/=20 000/microl) was 17 days (range 7-132). Day 100 and cumulative (18-month) transplant-related mortalities (TRMs) were 5 and 22%. Twenty-four patients (60%) are alive (14 in complete remission or complete remission, unconfirmed/uncertain) with a median follow-up of 13 months (4-78). In all, 16 patients expired (TRM n=8, disease progression n=8). FM patients had better overall survival (73 vs 39% at 18 months; P=0.03), and a trend towards better progression-free survival (37 vs 21% at 18 months; P=0.2). RIC allo-SCT is feasible in relapsed/refractory HD patients with a low TRM. The intensity of the preparative regimen affects survival.

Adolescent↗
PubMed2005

Disease burden may identify patients more likely to benefit from second allogeneic hematopoietic stem cell transplantation to treat relapsed acute myelogenous leukemia.

The major cause of failure after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) is disease relapse or progression. We analyzed the outcome of second HSCT for treatment of patients with relapsed, refractory AML/myelodysplastic syndrome (MDS) at our institution. A total of 72 patients were eligible for this analysis. In all, 25 (35%) patients received salvage chemotherapy prior to the second transplant procedure and only two (3%) patients were in complete remission at the time of the second transplant. A total of 20 patients (28%) had low leukemia burden as measured by the absence of peripheral blood blasts and <or=5% blasts in the bone marrow at the time of the second transplant. Although, the overall median survival after the second transplant was 6 months, a subset of patients who had low leukemia burden at the time of the second transplant had a 5-year survival of 25 vs 12% in those with a high leukemia burden. Thus, a second transplant may offer the possibility of long-term disease control in a subset of patients who have a 'low bulk' disease at the time of transplantation.

Adolescent↗
PubMed2005

The early referral for reduced-intensity stem cell transplantation in patients with Ph1 (+) chronic myelogenous leukemia in chronic phase in the imatinib era: results of the Latin American Cooperative Oncohematology Group (LACOHG) prospective, multicenter study.

Using a reduced-intensity stem cell transplantation (RIST) schedule, 24 patients with Philadelphia (Ph1) (+) chronic myelogenous leukemia (CML) in first chronic phase (CP) were prospectively allografted in four Latin American countries: México, Brazil, Colombia and Venezuela, using HLA-identical siblings as donors. The median age of the patients was 41 years (range 10-71 years); there were eight females. Patients received a median of 4.4 x 10(6)/kg CD34 cells. The median time to achieve above 0.5 x 10(9)/l granulocytes was 12 days, range 0-41 days, and the median time to achieve above 20 x 10(9)/l platelets was also 12 days, range 0-45 days. In all, 22 patients are alive 81-830 (median 497) days after RIST. The 830-day probability of survival is 92%, and the median survival has not been reached, being beyond 830 days. A total of 11 patients (46%) developed acute graft-versus-host disease (GVHD), and seven of 23 (30%) developed chronic GVHD. Two patients died 43 and 210 days after RIST, one as a result of sepsis and the other of chronic GVHD. The 100-day mortality was 4.4%, and transplant-related mortality was 8%. RIST for patients with CML in CP appears to be an adequate therapeutic option.

Adolescent↗
PubMed2005

Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality in haematopoietic transplant recipients. Sirolimus is a macrocyclic triene antibiotic with immunosuppressive, antifungal and antitumour properties, that has activity in the prevention and treatment of acute GVHD. We conducted a phase II trial of sirolimus combined with tacrolimus and methylprednisolone in patients with steroid-resistant cGVHD. Thirty-five patients who developed GVHD after day 100 post-transplant were studied. Six patients had a complete response and 16 a partial response with an overall response rate of 63%. Major adverse events related to the combination of tacrolimus and sirolimus were hyperlipidaemia, renal dysfunction and cytopenias. Four patients had thrombotic microangiopathy (TMA) and 27 (77%) had infectious complications. The median survival for the whole group was 15 months. A significantly better outcome was observed in patients with a platelet count > or = 100 x 10(9)/l, as well as in those with true chronic manifestations of GVHD compared to those with acute GVHD beyond day 100. Controlled trials comparing this approach with alternative strategies to determine which can best achieve the goal of GVHD-free survival are warranted.

Adult↗
PubMed2004

Outcomes of autologous stem cell transplantation in patients with multiple myeloma who received dexamethasone-based nonmyelosuppressive induction therapy.

High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) improves survival in myeloma (MM). The role of induction therapy on outcomes of ASCT in MM has not been systematically studied. Nonmyelosuppressive (NMS) steroid-based induction can be used in MM, with the potential of reducing neutropenias and other toxic effects prior to ASCT. NMS induction however could be associated with poorer outcomes if disease control or stem cell collection were inadequate. We studied outcomes of 136 MM patients who underwent HDC and ASCT as part of their initial therapy between March 1998 and December 2000. Of these, 46 received HDC and ASCT without any exposure to myelosuppressive agents, 39 received myelosuppressive therapy for disease control and/or stem cell collection, and 51 received alkylating agent-based initial treatment. We compared OS and EFS rates, stem cell collectability, and contamination of the grafts with monoclonal plasma cells. After a median of 33 months, response rates, EFS and OS rates were comparable in the three groups of patients. Adequacy of stem cell collection and plasma cell contamination were similar. Our data support the hypothesis that NMS induction for patients with MM is safe and effective and does not compromise the results of HDC.

Dexamethasone↗
PubMed2004

Prognostic factors for disease progression after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for recurrent or refractory Hodgkin's lymphoma.

Our purpose was to study the risk factors associated with disease progression after high-dose chemotherapy followed by autologous stem cell transplantation in patients with recurrent or refractory Hodgkin's lymphoma (HL). We analyzed the long-term outcome of 184 patients with recurrent or refractory HL who underwent autologous hematopoietic stem cell transplantation. At the time of transplantation, 82 patients were in first relapse or second remission, 46 patients were refractory to the primary induction chemotherapy, and 56 patients were beyond first relapse or second remission. In 64 patients, the disease had proved refractory to the chemotherapy regimen administered immediately prior to transplantation. The median follow-up of patients who were alive and free of disease at the time of this report was 8.9 years (range, 0.1-19.0 years). At 10 years, the overall and disease-free survival rates were 34% (95% CI 27-42) and 29% (95% CI 22-36) respectively. The major cause of treatment failure was disease relapse. Chemotherapy resistance prior to transplantation, advanced stage, and higher number of chemotherapy regimens administered prior to transplantation were adverse prognostic factors for disease progression. We conclude that autologous transplantation is an effective salvage treatment for recurrent HL.

Acute Disease↗
PubMed2004

CD8+ cell depletion of donor lymphocyte infusions using cd8 monoclonal antibody-coated high-density microparticles (CD8-HDM) after allogeneic hematopoietic stem cell transplantation: a pilot study.

A CD8 murine monoclonal antibody-coated high-density microparticle (HDM) has been developed, which allows for the rapid depletion of CD8+ T cells from apheresis products by gravity sedimentation. We conducted a study to determine the efficacy and safety of CD8 depletion of donor lymphocyte infusions (DLI) to treat relapse after stem cell transplantation using the Eligix CD8-HDM Cell Separation System. Patients were targeted to receive 3 x 10(7) CD4+ T cells/kg. Nine patients were enrolled, three with CML, three myeloma, two CLL, and one NHL. A median of 1 x 10(10) mononuclear cells were obtained by apheresis and processed. The median depletion of CD8+ cells was 99.3% (97.8->99.5%). CD8 depletion was highly specific, with a median recovery of CD4+ cells of 75%. A median of 2.9 x 10(7) CD4+ cells/kg was infused. No infusional toxicity was noted. All CML patients achieved a complete molecular remission. A CLL patient demonstrated a complete response. One patient developed GVHD (grade II acute GVHD and subsequently chronic GVHD). The CD8-HDM Cell Separation System appears to be highly selective and effective in depleting CD8+ T cells from DLI apheresis products, and CD8-depleted DLI is capable of mediating a graft-versus-leukemia effect while minimizing GVHD.

Adult↗
PubMed2004

Clinical outcomes with intensive therapy for patients with primary resistant multiple myeloma.

Clinical outcomes were evaluated in 89 consecutive patients with multiple myeloma that had not responded to dexamethasone-based primary therapy, who received early intensive therapy supported by autologous stem cell transplantation. Results were compared with those of 45 comparable patients who refused or were unable to receive intensive treatment for socioeconomic reasons. Following high-dose therapy, the response rate was 69% including 16% with CR. Survival of 14 patients with CR (median >7.0 years) was significantly longer than those of 47 patients with PR (median 4.5 years) or of 28 patients who remained NR (median 2.2 years). CR occurred in 43% of patients with serum myeloma protein <1.5 gm/dl, in contrast to 7% of those with higher values, a finding similar to that observed previously for patients consolidated in PR. No prognostic factor was associated with PR and, in view of the high frequencies of PR or CR, all patients with primary resistant myeloma should be considered for early intensive therapy. The limited improvement of lifespan and disease-free survival for those in PR indicated the need for further treatment to achieve CR, the major surrogate marker for long survival.

Adult↗
PubMed2003

Extracorporeal photopheresis therapy in the management of steroid-refractory or steroid-dependent cutaneous chronic graft-versus-host disease after allogeneic stem cell transplantation: feasibility and results.

We conducted a retrospective analysis of all allogeneic stem cell transplantation (ASCT) patients started on extracorporeal photopheresis (ECP) for the management of steroid-dependent (SD) or steroid-refractory (SR) cutaneous chronic graft-versus-host disease (cGVHD) following ASCT during a 36-month period (9/98-8/01). Only SD or SR patients who were treated by ECP after day 100 and who received at least 4 weeks of ECP were considered evaluable for this analysis. Out of 64 ASCT patients reviewed, 32 patients met the inclusion criteria. All 32 patients had been previously treated with systemic corticosteroids with 11 (34%) being SR and 21 (66%) SD. Cutaneous cGVHD was extensive in 28 patients (88%) and was accompanied by visceral (hepatic, gastrointestinal) cGVHD in 23 patients (72%). The 32 evaluated patients had received a median of three prior therapies before ECP, most commonly systemic corticosteroids, tacrolimus, and mycophenolate mofetil. Patients received a median of 36 ECP sessions (range 12-98) over a median of 5.3 months (range 1-28), with a median of six sessions per month. The complete response (CR) rate was 22% (n=7) and the partial response rate was 34% (n=11). In all, 28 patients were on systemic corticosteroid therapy at ECP initiation and 18 patients achieved 50% dose reduction while on ECP, yielding a 64% steroid-sparing response rate. Of seven CRs, five are ongoing. A total of 11 (34%) patients have died after ECP, with all cases due to visceral cGVHD or cGVHD-related infectious complications. All 21 surviving patients remain on at least some immunosuppressive cGVHD therapy (including ECP in eight). Overall, ECP displays a substantial response rate and, in particular, steroid-sparing activity in SR/SD extensive cutaneous cGVHD. However, most patients continue to require at least some chronic therapy and cGVHD-related morbidity and mortality remain high.

Adolescent↗
PubMed2002

Update on non-myeloablative stem cell transplantation for hematologic malignancies.

Allogeneic stem cell transplantation is an established treatment modality for a variety of hematologic malignancies. Unfortunately it carries a high risk of complications and toxicities related to the intensive preparative regimen which is traditionally used for pre-transplant myeloablation and the graft versus host disease, which may be life threatening. Thus allogeneic stem cell transplantation has been used only for younger patients with a good performance status, excluding many other potential candidates due to advanced age or comorbid conditions. Non ablative or reduced intensity preparative regimens for allogeneic stem cell transplantation (NST) have been proposed as a strategy that would allow exploiting the graft versus tumor effect of allogeneic transplantation without the toxicity of myeloablative therapy. After more than five years of cumulative clinical experience, it is now well established that NST is a feasible treatment option for patients with suboptimal performance status and is mostly effective in slow proliferating malignancies, which gives time for a graft versus malignancy effect to take place. Additionally achievement of stable donor cell engraftment with NSTs provides a platform for adoptive immune cell treatments and may allow to extend indications of stem cell transplantation in the future.

Antineoplastic Agents↗
PubMed2002

Critical review on non-myeloablative stem cell transplantation (NST).

Allogeneic stem cell transplantation is an established treatment modality for a variety of hematologic malignancies. Unfortunately, it carries a high risk of complications and toxicities related to the intensive preparative regimen which is traditionally used for pre-transplant myeloablation and the graft versus host disease, which may be life threatening. Thus allogeneic stem cell transplantation has been used only for younger patients with a good performance status, excluding many other potential candidates due to advanced age or comorbid conditions. Using reduced intensity preparative regimens for allogeneic stem cell transplantation (non-myeloablative stem cell transplantation (NST)) researchers attempted to overcome these barriers in patients' selection and tried to make hematopoietic stem cell (HSC) transplantation a safer procedure. The well-described graft versus malignancy effect would be the most curative element in this treatment. After more than 5 years of cumulative clinical experience, we know that NST is a feasible treatment option for patients with suboptimal performance status and is mostly effective in slow proliferating malignancies, which gives time for a graft versus malignancy effect to take place. Additionally achievement of stable donor cell engraftment with NSTs provides a platform for adoptive immune cell treatments and is promising for extended indications of stem cell transplantation in the future.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Stem cell transplantation (SCT) for Waldenstrom's macroglobulinemia (WM).

Waldenstrom's macroglobulinemia (WM) is a low-grade lymphoplasmacytoid malignancy of unknown etiology. It primarily affects elderly patients and is characterized by a monoclonal IgM component, varying degrees of cytopenias, lymphadenopathy and manifestations related to hyperviscosity syndromes. WM is usually treated with single agent nucleoside analogues or alkylating agents that often provide high response rates and durable remissions. Recurrence of the disease after primary therapy is not uncommon, and resistance to both alkylating agents and nucleoside analogs eventually emerges. Small numbers of patients have undergone high-dose chemotherapy (HDC) with either autologous (n = 24) or allogeneic (n = 6) stem cell transplantation (SCT) as treatment for this disease. Most patients in both groups achieved remission. Results are promising and a more in-depth analysis of possible applications of this treatment modality is attempted with this mini-review.

Adult↗