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 Mixed T-lymphoid chimerism after allogeneic bone marrow transplantation for hematologic malignancies of children is not correlated with relapse

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1921-1928 ◽  
Author(s):  
JE van Leeuwen ◽  
MJ van Tol ◽  
AM Joosten ◽  
JT Wijnen ◽  
PM Khan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Cell Lineage ◽  
Hematologic Malignancies ◽  
Mixed Chimerism ◽  
Cell Populations ◽  
Allogeneic Bone ◽  
Leukemia Relapse

Abstract We performed polymerase chain reaction-variable number of tandem repeats analysis of flow-sorted peripheral blood T-, B-, natural killer- , and myeloid cell populations (van Leeuwen et al, Br J Haematol 79:218, 1991) in 32 children following allogeneic bone marrow transplantation (BMT) for leukemia to evaluate the relationship between mixed lymphoid chimerism and leukemia relapse. Five patients showed a stable mixed chimerism pattern characterized by the presence of both recipient as well as donor type cells in all cell populations up to 1 year posttransplantation. Five others showed transient mixed chimerism in the T-lymphoid cell lineage. In one patient, host T cells persisted until leukemia relapse. The remaining 21 patients showed a complete chimerism throughout the period of investigation. Twenty-five of these patients were classified according to the presence (n = 10) or absence (n = 15) of recipient type T cells. Statistical analysis did not show significant differences in the distribution of a number of clinical variables between the two groups, nor in the actuarial survival (P = .11) and leukemia-free interval (P = .97). Therefore, these results suggest that persistence of recipient type T lymphoid cells after allogeneic BMT for hematologic malignancies is not correlated with leukemia relapse. In addition, we observed that persistence of host cells within the original leukemia cell lineage and at the correct maturational stage was predictive for leukemia relapse in one case.

Trials With Impact on Clinical Management: First Line

2009 ◽  
Vol 19 (Suppl 2) ◽  
pp. S55-S62 ◽  
Author(s):  
Michael A. Bookman
Keyword(s):  
Ovarian Cancer ◽  
Cancer Biology ◽  
Treatment Options ◽  
Tumor Biology ◽  
Chemotherapy Resistance ◽  
Treatment Strategies ◽  
Weekly Dose ◽  
Primary Therapy ◽  
Phase 3 ◽  
Standard Regimen

Introduction:Advanced-stage epithelial ovarian cancer is generally managed with cytoreductive surgery and chemotherapy consisting of carboplatin and paclitaxel. Although initially responsive, most tumors recur and demonstrate progressive chemotherapy resistance. During the last 20 years, many thousands of women have participated in international front-line phase 3 trials that have contributed to our understanding of ovarian cancer biology and helped to define optimal treatment strategies. Emerging data from these trials need to be interpreted within an evolving paradigm of cancer biology, disease management, and availability of clinical resources.Methods:Survey of recent phase 3 trials and emerging principles of ovarian tumor biology.Results:There is no evidence that adding a third cytotoxic agent improves clinical outcomes. However, weekly dose-dense scheduling of paclitaxel appears superior to standard dosing.Conclusion:Primary therapy with carboplatin and paclitaxel remains a well-tolerated standard regimen, including the option of weekly paclitaxel dosing. Data are awaited from completed trials incorporating bevacizumab. Emerging biological paradigms will contribute to individualized treatment options in the future.

Hematopoietic recovery after allogeneic blood stem-cell transplantation compared with bone marrow transplantation in patients with hematologic malignancies.

1997 ◽  
Vol 15 (4) ◽  
pp. 1608-1616 ◽  
Author(s):  
Z S Pavletic ◽  
M R Bishop ◽  
S R Tarantolo ◽  
S Martin-Algarra ◽  
P J Bierman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Survival Rates ◽  
Human Leukocyte ◽  
Hematologic Malignancies ◽  
Allogeneic Blood ◽  
Allogeneic Bone ◽  
Hematopoietic Recovery

PURPOSE To compare hematopoietic recovery, duration of hospitalization, and 100-day survival in patients who received allogeneic-blood stem cells (BSC) or conventional allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS From December 1994 to August 1995, 21 patients participated in a phase II study of allogeneic BSC transplantation. Cells mobilized with granulocyte colony-stimulating factor (G-CSF; 5 micrograms/kg/ d) were collected from human leukocyte antigen (HLA)-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. G-CSF (10 micrograms/kg/d) was administered posttransplant. The outcomes were compared with 22 identically treated historical patients who received allogeneic BMT. RESULTS The median infused CD34+ cell and granulocyte-macrophage colony-forming unit (CFU-GM) content were 7.73 x 10(4)/kg and 41.6 x 10(4)/kg, respectively. The median time to a neutrophil count greater than 500/ microL was 11 days after BSC and 16.5 days after BMT (P = .0003). A trend toward faster platelet and RBC recovery after BSC was observed. BSC patients received fewer platelet transfusions: 10 versus 19 (P = .015). The median length of hospitalization was shorter after BSC transplantation: 25 versus 31.5 days (P = .0243). The 100-day survival rates were similar: 83% after BSC and 75% after BMT (P = .3585). The incidence of acute GVHD grade II to IV was 57% and 45% for BSC and BMT, respectively (P = .4654). CONCLUSION In comparison to BMT, allogeneic BSC transplantation may result in faster hematopoietic recovery, shorter hospital stay, and similar early survival. Whether allogeneic BSC are superior to bone marrow needs to be determined in randomized trials.

scholarly journals Managing Patients With TP53-Deficient Chronic Lymphocytic Leukemia

2017 ◽  
Vol 13 (6) ◽  
pp. 371-377 ◽  
Author(s):  
Jennifer Edelmann ◽  
John G. Gribben
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Clinical Investigation ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Clinical Trial Data ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Chromosome 17

Patients with chronic lymphocytic leukemia (CLL) having a chromosomal loss on the short arm of chromosome 17 including the TP53 gene locus (17p deletion) and/or having mutations in TP53 have a short overall survival and, until recently, limited treatment options. The recent introduction of two novel substance classes, B-cell receptor inhibitors and BH3 mimetics, into CLL treatment has provided enormous clinical progress in this previously difficult-to-treat patient subgroup characterized by high risk for treatment failure with standard chemoimmunotherapy and rapid disease progression. Compounds now approved for the treatment of TP53-deficient CLL are the two B-cell receptor inhibitors ibrutinib and idelalisib and the BH3 mimetic venetoclax. All three compounds were approved on the basis of favorable response rates that, importantly, revealed no differences between TP53-competent and TP53-deficient CLL cases. Using these compounds, longer-lasting remissions in patients with TP53-deficient CLL could be demonstrated for the first time. Whether TP53 alterations will maintain their significance as adverse prognostic factors in treatment strategies involving novel compounds needs to be assessed. This review provides an overview of current treatment options for 17p-deleted/ TP53-mutated CLL, including those compounds that are already approved by the US Food and Drug Administration or are under advanced clinical investigation. Available clinical trial data are discussed, as is the use of novel targeted treatment options in the context of transplant strategies, and an algorithm for off-study treatment of 17p-deficient CLL is suggested.

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.

Hemolytic-uremic syndrome following bone marrow transplantation in adults for hematologic malignancies

Blood ◽  
1991 ◽  
Vol 77 (8) ◽  
pp. 1837-1844 ◽  
Author(s):  
SN Rabinowe ◽  
RJ Soiffer ◽  
NJ Tarbell ◽  
D Neuberg ◽  
AS Freedman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Hemolytic Uremic Syndrome ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Subsequent Development ◽  
Hematologic Malignancies ◽  
Allogeneic Bone ◽  
Uremic Syndrome

One hundred and sixty eight adult patients with B-cell non-Hodgkin's lymphoma (NHL) and other hematologic malignancies who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic-uremic syndrome (HUS). All patients were conditioned with cyclophosphamide and total body irradiation. When examined at 3-month intervals for the first year post-BMT, all patients had uniform measurements of hematocrit (Hct) and serum creatinine. Sixteen patients who initially exhibited Hct and creatinine values that were normal range for the BMT populations developed a sudden decrease in Hct and increase in creatinine between 3 and 11 months post-BMT and fulfilled the clinical and laboratory criteria for HUS. None of these patients had known active cytomegalovirus infection, graft-versus-host disease, or cyclosporine administration. The degree of decrease in Hct and creatinine elevation ranged from solely laboratory abnormalities to a clinically significant syndrome. Twelve of the 16 patients developed acute clinical complications of congestive heart failure, hypertension (HTN), or peripheral edema. Twelve patients required red blood cell support, whereas only four patients required platelet transfusions. Both hemolytic anemia and thrombocytopenia have resolved in virtually all cases. At a mean follow up of 18 months postdiagnosis, creatinine elevations have persisted along with HTN. All patients have survived without life-threatening long-term sequelae. With the increasing use of BMT as a curative modality for patients with hematologic malignancies, it becomes important to prospectively monitor patients for the development of HUS and its potential long-term impact on renal function.

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