Oral Prednisolone Produces a Durable Response in Pediatric Myelodysplastic Syndromes (MDS).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4906-4906
Author(s):  
Mammen Chandy ◽  
Biju George ◽  
Vikram Mathews ◽  
Auro Viswabandya ◽  
Ashish Bajel ◽  
...  
Keyword(s):  
Median Duration ◽  
Treatment Options ◽  
Allogeneic Bone Marrow Transplantation ◽  
Oral Prednisolone ◽  
Complete Response ◽  
Allogeneic Bone ◽  
Durable Response ◽  
Duration Of Symptoms ◽  
Transfusion Independence ◽  
Progression Of Disease

Abstract Treatment options for children with MDS are limited except for allogeneic bone marrow transplantation. We present our experience with the use of long duration corticosteroids in children with MDS. Fifty five children (age< 15 years) with pediatric MDS or myelofibrosis treated between 1991–2004 with corticosteroids were analyzed. All of these patients presented with cytopenia involving one or more lineages and a hypercellular marrow with dysplasia and increased reticulin. Prednisolone was started at 1 mg/kg daily or on alternate days for a period of 1–2 months. If there was no response, steroids were rapidly tapered and stopped. In children who showed a response, the steroids were slowly tapered to alternate day steroids and stopped over a period of 6–12 months. In patients who had relapse of symptoms on tapering, the dose of steroids was increased to previous levels and then tapered at a much slower rate. The median age was 3 years (range: 3 months – 14 years) with 36 males and 19 females. Forty six has pediatric MDS while 10 had pediatric myelofibrosis. The median duration of symptoms prior to starting steroids was 7 months (range: 1–24). Forty one patients (74.5%) showed a response with 31 (56.4%) showing a complete response while 10 patients (18.1%) showed a partial response with improvement in counts and transfusion independence. Fourteen patients (25.5%) showed no improvement and continued to be transfusion dependant. Fourteen of the 41 patients (34%) who responded to steroids relapsed on tapering of steroids but showed response to repeat courses of steroids. The median duration of steroid use in patients who have responded is 12 months (range: 1 – 96). None of the patients had any serious side effects including infections, hypertension or diabetes except one patient who developed disseminated tuberculosis 12 months after stopping steroids. Nine patients have shown progression of disease while 1 patient developed features of SLE 24 months after diagnosis of MDS. At a median follow up of 34 months (range: 4– 120), 32 patients (58%) are alive with 27 (49%) in complete remission [14 off treatment, 13 on treatment] and 5 in partial remission but transfusion independent. Prednisolone induces a durable response in children with MDS. The biological basis of this response needs to be evaluated.

Individualizing Treatment Decisions for Older Adults with Hematologic Malignancies

2013 ◽  
pp. 208-219
Author(s):  
Heidi D. Klepin ◽  
David Rizzieri ◽  
Antonio Palumbo ◽  
Valeria Magarotto ◽  
Barbara Eichhorst
Keyword(s):  
Older Adults ◽  
Treatment Options ◽  
Allogeneic Bone Marrow Transplantation ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Allogeneic Bone ◽  
Functional Impairments ◽  
Therapeutic Decisions

Hematologic malignancies are a common cause of morbidity and mortality among older adults, who represent the majority of patients diagnosed with these diseases. Treatment options and disease outcomes have improved in recent years because of the development of novel treatment strategies and the design of elderly-specific clinical trials. Despite this, extrapolation of clinical trial data to patients routinely seen in practice is challenging because of the presence of multimorbidity and functional impairments. Individualized treatment decision making requires not only an understanding of underlying tumor biology but also careful estimation of an older patient's anticipated ability to withstand the stresses of therapy. This article will discuss approaches to standardizing patient assessment strategies and tailoring therapeutic decisions for older adults with hematologic malignancies with a focus on acute myeloid leukemia (AML), allogeneic bone marrow transplantation, multiple myeloma (MM), and chronic lymphocytic leukemia (CLL).

scholarly journals A Prospective Phase II Study Evaluating Intraoperative Electrochemotherapy of Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3778
Author(s):  
Mihajlo Djokic ◽  
Maja Cemazar ◽  
Masa Bosnjak ◽  
Rok Dezman ◽  
David Badovinac ◽  
...  
Keyword(s):  
Clinical Study ◽  
Phase Ii ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Complete Response ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Durable Response ◽  
Phase Ii Clinical Study ◽  
Prospective Phase

The aim of this clinical study was to investigate the effectiveness and long-term safety of electrochemotherapy as an emerging treatment for HCC in patients not suitable for other treatment options. A prospective phase II clinical study was conducted in patients with primary HCC who were not suitable for other treatment options according to the Barcelona Clinic Liver Cancer classification. A total of 24 patients with 32 tumors were treated by electrochemotherapy. The procedure was effective, feasible, and safe with some procedure-related side effects. The responses of the 32 treated nodules were: 84.4% complete response (CR), 12.5% partial response (PR), and 3.1% stable disease (SD). The treatment was equally effective for nodules located centrally and peripherally. Electrochemotherapy provided a durable response with local tumor control over 50 months of observation in 78.0% of nodules. The patient responses were: 79.2% CR and 16.6% PR. The median progression-free survival was 12 months (range 2.7–50), and the overall survival over 5 years of observation was 72.0%. This prospective phase II clinical study showed that electrochemotherapy was an effective, feasible, and safe option for treating HCC in patients not suitable for other treatment options.

Prospective Trial of Chemotherapy and Donor Leukocyte Infusions for Relapse of Advanced Myeloid Malignancies After Allogeneic Stem-Cell Transplantation

2002 ◽  
Vol 20 (2) ◽  
pp. 405-412 ◽  
Author(s):  
John E. Levine ◽  
Thomas Braun ◽  
Samuel L. Penza ◽  
Patrick Beatty ◽  
Kenneth Cornetta ◽  
...  
Keyword(s):  
Allogeneic Bone Marrow Transplantation ◽  
Prospective Trial ◽  
Complete Response ◽  
Allogeneic Bone ◽  
Significant Treatment ◽  
Term Survival ◽  
Myeloid Malignancies ◽  
Entire Cohort ◽  
Treatment Related Mortality ◽  
Related Mortality

PURPOSE: Patients with advanced myeloid malignancies who experience relapse after allogeneic bone marrow transplantation (BMT) have a poor prognosis. Long-term survival after chemotherapy alone, second myeloablative transplant, or donor leukocyte infusions (DLIs) alone is unusual. DLIs may have minimal effectiveness in advanced disease because adequate cellular responses are not able to develop in the presence of bulky, fast-growing disease. A chemotherapy strategy was used to debulk disease before administration of granulocyte colony-stimulating factor (G-CSF)–primed DLIs. PATIENTS AND METHODS: Sixty-five patients experiencing hematologic relapse of myeloid malignancy after HLA-matched sibling BMT were prospectively treated with cytarabine-based chemotherapy, then G-CSF–primed DLIs. No prophylactic immunosuppression was provided. RESULTS: Twenty-seven of 57 assessable patients experienced a complete response. Graft-versus-host disease (GVHD) was observed in 56% of the patients. Treatment-related mortality was 23%. Overall survival at 2 years for the entire cohort was 19%. Patients with a complete response were more likely to survive, with 1- and 2-year survival rates of 51% and 41%, respectively, with a median follow-up of more than 2 years. The 1-year survival for nonresponders was 5%. A posttransplant remission lasting more than 6 months before relapse was associated with a higher likelihood of response. GVHD was not required for durable remission. CONCLUSION: Salvage treatment with chemotherapy before DLI can help some patients with advanced myeloid relapse and is not dependent on GVHD. Patients with short remissions after BMT are unlikely to benefit from this approach, and the approach is associated with significant treatment-related mortality. Modifications of this approach or entirely different approaches will be required for most patients with this difficult clinical problem.

Complete response to donor lymphocyte infusion in multiple myeloma is associated with antibody responses to highly expressed antigens

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 656-663 ◽  
Author(s):  
Roberto Bellucci ◽  
Catherine J. Wu ◽  
Sabina Chiaretti ◽  
Edie Weller ◽  
Faith E. Davies ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Chronic Gvhd ◽  
Allogeneic Bone Marrow Transplantation ◽  
Complete Response ◽  
Donor Lymphocyte Infusion ◽  
Antibody Responses ◽  
Cdna Expression Library ◽  
Allogeneic Bone ◽  
Serum Samples ◽  
Expression Library

Abstract The ability of donor lymphocyte infusions (DLIs) to induce complete responses (CRs) in patients with relapsed myeloma after allogeneic bone marrow transplantation (BMT) provides clear evidence of an effective graft-versus-myeloma (GVM) response. To identify target antigens of the GVM response, we screened a myeloma cDNA expression library with post-DLI serum from 4 patients with myeloma who achieved CR after DLI and 1 patient who was in CR before DLI. We identified a panel of 13 gene products reactive with post-DLI serum but negative with pre-DLI and pre-BMT serum. Antibodies to these proteins were not detected in the sera of 10 patients who underwent allogeneic BMT without DLI and 5 patients with acute graft-versus-host disease (GVHD). Minimal reactivity with these proteins was detected in the sera of 20 healthy donors and 20 patients with chronic GVHD. In contrast, 5 of these proteins were recognized by more than 1 myeloma DLI responder. Testing of serial serum samples showed an association between antibody response and time of best response after DLI. The expression of these genes was evaluated in primary myeloma cells and in normal plasma cells. This study demonstrates that the GVM response is associated with antibody responses to highly expressed myeloma-associated antigens.

Use of octreotide in the symptomatic management of diarrhea induced by graft-versus-host disease in patients with hematologic malignancies.

1997 ◽  
Vol 15 (11) ◽  
pp. 3350-3354 ◽  
Author(s):  
C Ippoliti ◽  
R Champlin ◽  
N Bugazia ◽  
D Przepiorka ◽  
J Neumann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Graft Versus Host Disease ◽  
Allogeneic Bone Marrow Transplantation ◽  
Cost Effective ◽  
Complete Response ◽  
Allogeneic Bone ◽  
Peripheral Blood Stem Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Days Of Therapy

PURPOSE Diarrhea associated with acute gastrointestinal (GI) graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) can result in severe morbidity and mortality. A pilot study was conducted to evaluate the efficacy and toxicity of octreotide in the management of diarrhea in patients with GVHD after allogeneic BMT. PATIENTS AND METHODS Twenty-one patients entered the study. Patients received either peripheral-blood stem cells (n = 13) or bone marrow (n = 8). Seven patients had grade 4, 13 grade 3, and one grade 2 GVHD. Intravenous (I.V.) octreotide 500 microg every 8 hours for 7 days was administered. Octreotide treatment was discontinued if no response was observed after 7 days or for grade 4 toxicity. RESULTS Fifteen (71%) of 21 treated patients had a complete response within 7 days of the initiation of octreotide; three (14%) had a partial response and three (14%) failed to respond to treatment. Toxicities were minimal; hyperglycemia was seen in four patients and one patient developed a partial ileus. Octreotide was discontinued and the ileus resolved within 48 hours. CONCLUSION If initiated early in the course of GI GVHD, octreotide appears to be an effective, well-tolerated agent in reducing severe voluminous diarrhea. Octreotide should be discontinued within 24 hours after the resolution of diarrhea to avoid the development of ileus. Because no additional reduction in the volume of diarrhea occurred after 7 days of therapy, continuation of the drug beyond this time is not cost effective.

scholarly journals Recent advances in the pathogenesis and treatment of paroxysmal nocturnal hemoglobinuria

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 209 ◽  
Author(s):  
Lucio Luzzatto
Keyword(s):  
Stem Cells ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Treatment Options ◽  
Surface Membrane ◽  
Allogeneic Bone Marrow Transplantation ◽  
Thrombosis Prophylaxis ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Complement Regulatory Proteins ◽  
Inactivating Mutation

Paroxysmal nocturnal hemoglobinuria (PNH) is a very rare disease that has been investigated for over one century and has revealed unique aspects of the pathogenesis and pathophysiology of a hemolytic anemia. PNH results from expansion of a clone of hematopoietic cells that, as a consequence of an inactivating mutation of the X-linked genePIG-A, are deficient in glycosylphosphatidylinositol (GPI)-linked proteins: since these include the surface membrane complement-regulatory proteins CD55 and CD59, the red cells arising from this clone are exquisitely sensitive to lysis by activated complement. Until a decade ago, the treatment options for PNH were either supportive treatment – often including blood transfusion, anti-thrombosis prophylaxis, and sometimes thrombolytic therapy – or allogeneic bone marrow transplantation. Since 2007, PNH has received renewed and much wider attention because a new form of treatment has become available, namely complement blockade through the anti-C5 monoclonal antibody eculizumab. This brief review focuses on two specific aspects of PNH: (1) response to eculizumab, variability of response, and how this new agent has impacted favorably on the outlook and on the quality of life of patients; and (2) with respect to pathogenesis, new evidence supports the notion that expansion of the PNH clone results from T-cell-mediated auto-immune damage to hematopoietic stem cells, with the GPI molecule as target. Indeed, GPI-specific CD8+ T cells – which have been identified in PNH patients – would spare selectively GPI-negative stem cells, thus enabling them to re-populate the marrow of a patient who would otherwise have aplastic anemia.

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