272 results on '"Singhal, A."'
Search Results
2. Factors predicting survival following alloSCT in patients with therapy-related AML and MDS: a multicenter study
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Baranwal, Anmol, Chhetri, Rakchha, Yeung, David, Clark, Matthew, Shah, Syed, Litzow, Mark R., Hogan, William J., Mangaonkar, Abhishek, Alkhateeb, Hassan B., Singhal, Deepak, Cibich, Alia, Bardy, Peter, Kok, Chung H., Hiwase, Devendra K., and Shah, Mithun Vinod
- Abstract
Therapy-related myeloid neoplasms (t-MN) are aggressive myeloid neoplasms. Factors predicting post-allogeneic stem cell transplant (alloSCT) survival are not well-known. We studied the prognostic utility of factors at: t-MN diagnosis, pre-alloSCT, and post-alloSCT. Primary endpoints were 3-year overall survival (OS), relapse incidence (RI), and non-relapse mortality (NRM). Post-alloSCT OS did not differ between t-MDS and t-AML (20.1 vs. 19.6 months, P= 1), though t-MDS had a significantly higher 3-year RI compared to t-AML (45.1% vs. 26.9%, P= 0.03). In t-MDS, the presence of monosomy 5 (HR 3.63, P= 0.006) or monosomy 17 (HR 11.81, P= 0.01) pre-alloSCT were associated with higher RI. Complex karyotype was the only factor adversely influencing survival at all the timepoints. The inclusion of genetic information yielded 2 risk-categories: high-risk defined by the presence of pathogenic variants (PV) in (TP53/BCOR/IDH1/GATA2/BCORL1)and standard-risk (remainder of the patients) with 3-year post-alloSCT OS of 0% and 64.6%, respectively (P= 0.001). We concluded that while alloSCT was curative in a subset of t-MN patients, outcomes remained poor, specifically in the high-risk category. t-MDS patients, especially those with persistent disease pre-alloSCT were at increased risk of relapse. Disease-related factors at t-MN diagnosis were the most prognostic of post-alloSCT survival; utility of factors available later in the course, was incremental.
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- 2023
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3. Actual or ideal body weight to calculate CD34+ cell dose in patients undergoing autologous hematopoietic SCT for myeloma?
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Singh, V, Krishnamurthy, J, Duffey, S, Meagher, R, Villa, M, Monreal, J, Evens, A, Frankfurt, O, Altman, J, Gordon, L, Tallman, M, Williams, S, Winter, J, Singhal, S, and Mehta, J
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- 2009
4. Current status of autologous hematopoietic stem cell transplantation in myeloma
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Mehta, J and Singhal, S
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- 2008
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5. The role of maintenance chemotherapy after autotransplantation for acute lymphoblastic leukemia in first remission: single-center experience of 100 patients
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Sirohi, B, Powles, R, Treleaven, J, Kulkarni, S, Saso, R, Potter, M, Ethell, M, Morgan, G, Singhal, S, and Mehta, J
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- 2008
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6. High-dose chemotherapy and autologous hematopoietic stem cell transplantation in myeloma patients under the age of 65 years
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Mehta, J and Singhal, S
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- 2007
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7. Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole
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Trifilio, S, Singhal, S, Williams, S, Frankfurt, O, Gordon, L, Evens, A, Winter, J, Tallman, M, Pi, J, and Mehta, J
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- 2007
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8. Rigorous administration of methotrexate and outcome of allogeneic blood stem cell transplantation
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Mehta, J and Singhal, S
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- 2007
9. Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially?
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Mehta, J, Gordon, L I, Tallman, M S, Winter, J N, Evens, A O, Frankfurt, O, Williams, S F, Grinblatt, D, Kaminer, L, Meagher, R, and Singhal, S
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- 2006
10. Reduced-dose rasburicase (recombinant xanthine oxidase) in adult cancer patients with hyperuricemia
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Trifilio, S, Gordon, L, Singhal, S, Tallman, M, Evens, A, Rashid, K, Fishman, M, Masino, K, Pi, J, and Mehta, J
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- 2006
11. Ideal rather than actual body weight should be used to calculate cell dose in allogeneic hematopoietic stem cell transplantation
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Singhal, S, Gordon, L I, Tallman, M S, Winter, J N, Evens, A O, Frankfurt, O, Williams, S F, Grinblatt, D, Kaminer, L, Meagher, R, and Mehta, J
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- 2006
12. Use of total leukocyte and platelet counts to guide stem cell apheresis in healthy allogeneic donors treated with G-CSF
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Tomblyn, M, Gordon, L I, Singhal, S, Tallman, M S, Williams, S, Winter, J N, Evens, A, and Mehta, J
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- 2005
13. An elective single autograft with high-dose melphalan: single-center study of 451 patients
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Sirohi, B, Powles, R, Mehta, J, Rudin, C, Kulkarni, S, Horton, C, Saso, R, Singhal, S, and Treleaven, J
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- 2005
14. Can the stem cell mobilization technique influence CD34+ cell collection efficiency of leukapheresis procedures in patients with hematologic malignancies?
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Gidron, A, Verma, A, Doyle, M, Boggio, L, Evens, A, Gordon, L, Singhal, S, Tallman, M, Williams, S, Winter, J, and Mehta, J
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- 2005
15. Reassessing autotransplantation for acute myeloid leukaemia in first remission - a matched pair analysis of autologous marrow vs peripheral blood stem cells
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Sirohi, B, Powles, R, Kulkarni, S, Rudin, C, Frassoni, F, Bacigalupo, A, Singhal, S, Vaidya, S, Labopin, M, Michallet, M, Blaise, D, Reiffers, J, Meloni, G, Rio, B, Treleaven, J, Horton, C, and Mehta, J
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- 2004
16. High-dose melphalan and autotransplantation followed by post transplant maintenance chemotherapy for acute lymphoblastic leukemia in first remission
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Mehta, J, Powles, R, Sirohi, B, Treleaven, J, Kulkarni, S, and Singhal, S
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- 2004
17. How long after neutrophil recovery should myeloid growth factors be continued in autologous hematopoietic stem cell transplant recipients?
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Verma, A, Pedicano, J, Trifilio, S, Singhal, S, Tallman, M, Winter, J, Williams, S, Gordon, L, Monreal, J, and Mehta, J
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- 2004
18. Bone marrow transplantation from partially HLA-mismatched family donors for acute leukemia: single-center experience of 201 patients
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Mehta, J, Singhal, S, Gee, A P, Chiang, K-Y, Godder, K, van Rhee, F, DeRienzo, S, O'Neal, W, Lamb, L, and Henslee-Downey, P J
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- 2004
19. Ideal or actual body weight to calculate CD34+ cell doses for allogeneic hematopoietic stem cell transplantation?
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Cilley, J, Rihn, C, Monreal, J, Gordon, L I, Singhal, S, Tallman, M, Williams, S, Winter, J, and Mehta, J
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- 2004
20. Impact of cytogenetics on the outcome of autotransplantation for acute myeloid leukemia in first remission: is the benefit of intensive pretransplant therapy limited to patients with good karyotypes?
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Mehta, J, Powles, R, Sirohi, B, Treleaven, J, Swansbury, G J, Kulkarni, S, Saso, R, and Singhal, S
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- 2003
21. Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease
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Kulkarni, S, Powles, R, Sirohi, B, Treleaven, J, Saso, R, Horton, C, Atra, A, Ortin, M, Rudin, C, Goyal, S, Sankpal, S, Meller, S, Pinkerton, C R, Mehta, J, and Singhal, S
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- 2003
22. Haploidentical vs autologous hematopoietic stem cell transplantation in patients with acute leukemia beyond first remission
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Singhal, S, Henslee-Downey, P J, Powles, R, Chiang, K Y, Godder, K, Treleaven, J, Kulkarni, S, van Rhee, F, Sirohi, B, Pinkerton, C R, Meller, S, Jovanovic, B, and Mehta, J
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- 2003
23. Ideal or actual body weight to calculate CD34+ cell doses for autologous hematopoietic stem cell transplantation?
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Ali, M Y, Oyama, Y, Monreal, J, Winter, J N, Tallman, M S, Williams, S F, Singhal, S, Gordon, L I, and Mehta, J
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- 2003
24. Actual or ideal body weight to calculate CD34+ cell dose in patients undergoing autologous hematopoietic SCT for myeloma?
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Martin S. Tallman, Andrew M. Evens, Joanne Monreal, M. Villa, Seema Singhal, Olga Frankfurt, Jayesh Mehta, S. Duffey, Jairam Krishnamurthy, Leo I. Gordon, Stephanie F. Williams, Richard Meagher, V. Singh, Jessica K. Altman, and Jane N. Winter
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Cd34 cells ,Population ,Urology ,CD34 ,Antigens, CD34 ,Body weight ,Transplantation, Autologous ,Body Mass Index ,Internal medicine ,medicine ,Humans ,Platelet ,In patient ,education ,Melphalan ,Aged ,Retrospective Studies ,Transplantation ,education.field_of_study ,Hematology ,business.industry ,Body Weight ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Combined Modality Therapy ,Hematopoietic Stem Cell Mobilization ,Haematopoiesis ,Hematologic Neoplasms ,Female ,Multiple Myeloma ,business ,Biomarkers - Abstract
CD34+ cell dose calculations are usually based on actual body weight (ABW). We have shown that ideal body weight (IBW) may provide a better basis for this in a small population of patients with hematologic malignancies. This was studied further in 514 myeloma autografts. The CD34+ cell doses (10(6)/kg) by IBW and ABW were 1.37-39.36 (median 6.03) and 1.15-29.67 (median 4.84), respectively. IBW-based cell doses correlated slightly better with engraftment than ABW-based doses (higher r(2)): 0.5 x 10(9)/l neutrophils 0.83 versus 0.82, 1.0 x 10(9)/l neutrophils 0.78 versus 0.77, 20 x 10(9)/l platelets 0.54 versus 0.53 and 50 x 10(9)/l platelets 0.57 versus 0.55. When outliers (hematologic recovery in8 or16 days) were excluded, the findings were similar: 0.5 x 10(9)/l neutrophils 0.85 versus 0.84, 1.0 x 10(9)/l neutrophils 0.85 versus 0.84, 20 x 10(9)/l platelets 0.86 versus 0.85 and 50 x 10(9)/l platelets 0.85 versus 0.84. CD34+ cell doses based on IBW as well as ABW significantly affected engraftment when analyzed separately as continuous variables. However, when analyzed together, only the dose based on IBW retained significance. We conclude that calculation of CD34+ cell numbers for autotransplantation should be based on IBW.
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- 2008
25. Current status of autologous hematopoietic stem cell transplantation in myeloma
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Jayesh Mehta and Seema Singhal
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Melphalan ,medicine.medical_specialty ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,immune system diseases ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Lenalidomide ,Transplantation ,Chemotherapy ,business.industry ,Bortezomib ,Hematopoietic Stem Cell Transplantation ,Hematology ,Autotransplantation ,Surgery ,Thalidomide ,Treatment Outcome ,surgical procedures, operative ,Multiple Myeloma ,business ,medicine.drug - Abstract
High-dose melphalan with autologous hematopoietic SCT (HSCT) improves response rates and survival in myeloma. This is despite the fact that unlike other hematologic malignancies treated with high-dose therapy and autotransplantation, autografted myeloma patients continue to relapse several years after transplantation and the procedure is not curative in the majority of patients. However, patients surviving for several years with essentially normal quality of life may be considered to be 'operationally cured.' Also, unlike with other hematologic malignancies relapsing after an autograft, recurrent disease can be treated with novel agents or repeat high-dose chemotherapy and autologous or allogeneic HSCT--and long-term survival is seen in a number of patients after relapse. Although tandem transplantation is clearly superior to a single autograft, it is unclear if this should be offered to all patients routinely or only to those not attaining CR after one transplant. It is also unclear if novel agents should be used before transplantation or reserved for relapse. Despite their excellent activity, there is no evidence that novel agents such as thalidomide, bortezomib and lenalidomide can replace high-dose chemotherapy and HSCT, and the best strategy is to use all options in all eligible patients at appropriate stages of the disease.
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- 2008
26. High-dose chemotherapy and autologous hematopoietic stem cell transplantation in myeloma patients under the age of 65 years
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Jayesh Mehta and Seema Singhal
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Adult ,Melphalan ,medicine.medical_specialty ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,chemistry.chemical_compound ,Recurrence ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Lenalidomide ,Transplantation ,Chemotherapy ,Bortezomib ,business.industry ,Patient Selection ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Survival Analysis ,Nitrogen mustard ,Surgery ,Thalidomide ,Treatment Outcome ,chemistry ,Multiple Myeloma ,business ,medicine.drug - Abstract
One or two cycles of high-dose chemotherapy with autologous hematopoietic stem cell transplantation have been shown to improve response rates and survival in myeloma. While this observation has largely been made in patients under the age of 65 years, there is evidence to suggest that the conclusions can be extrapolated to older individuals as well. In contrast to other hematologic malignancies treated with high-dose therapy, autografted myeloma patients continue to relapse several years after transplantation, and few patients are cured with this modality. However, up to a third of patients may be alive beyond a decade; some with excellent quality of life giving rise to the concept of 'operational cure'. Relapsing disease can be treated with novel agents or repeat high-dose chemotherapy and transplantation. The pressing questions to which answers are not obvious at the moment are whether tandem transplantation should be offered to all patients, and whether novel agents should be used before transplantation or reserved for relapse. Despite their excellent activity, there is no evidence so far that novel agents such as thalidomide, bortezomib and lenalidomide can replace high-dose chemotherapy and stem cell transplantation.
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- 2007
27. Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole
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Andrew M. Evens, Jane N. Winter, Jayesh Mehta, Stephanie F. Williams, J. Pi, Leo I. Gordon, Olga Frankfurt, Seema Singhal, Martin S. Tallman, and Steven Trifilio
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Male ,medicine.medical_specialty ,Antifungal Agents ,Itraconazole ,Premedication ,Aspergillosis ,Gastroenterology ,Zygomycosis ,Candida krusei ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Mycosis ,Voriconazole ,Transplantation ,biology ,Candida glabrata ,business.industry ,Data Collection ,Candidiasis ,Hematopoietic Stem Cell Transplantation ,Hematology ,Triazoles ,biology.organism_classification ,medicine.disease ,Surgery ,Pyrimidines ,Mycoses ,Drug Evaluation ,Female ,business ,medicine.drug - Abstract
Seventy-one allograft recipients receiving voriconazole, in whom complete clinical, microbiologic and pharmacokinetic data were available, were studied to determine the efficacy of voriconazole in preventing fungal infections. The length of voriconazole therapy was 6-956 days (median 133). The total number of patient-days on voriconazole was 13 805 ( approximately 38 years). A total of 10 fungal infections were seen in patients on voriconazole (18% actuarial probability at 1 year): Candida glabrata (n=5), Candida krusei (n=1), Cunninghamella (n=1), Rhizopus (n=2) and Mucor (n=1). Two of the four zygomycosis cases were preceded by short durations of voriconazole therapy, but prolonged itraconazole prophylaxis. The plasma steady-state trough voriconazole levels around the time the infection occurred were0.2,0.2, 0.33, 0.55, 0.63 and 1.78 microg/ml in the six candidiasis cases. Excluding the four zygomycosis cases, all the six candidiasis cases were seen among the 43 patients with voriconazole levels ofor =2 microg/ml and none among the 24 with levels of2 microg/ml (P=0.061). We conclude that voriconazole is effective at preventing aspergillosis. However, breakthrough zygomycosis is seen in a small proportion of patients. The role of therapeutic voriconazole monitoring with dose adjustment to avoid breakthrough infections with fungi that are otherwise susceptible to the drug needs to be explored prospectively.
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- 2007
28. An elective single autograft with high-dose melphalan: single-center study of 451 patients
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Jennifer Treleaven, Claudius Rudin, R. L. Powles, Samar Kulkarni, Jayesh Mehta, Radovan Saso, Bhawna Sirohi, Clive Horton, and Seema Singhal
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Adult ,Male ,Melphalan ,medicine.medical_specialty ,Vincristine ,medicine.medical_treatment ,Single Center ,Transplantation, Autologous ,chemistry.chemical_compound ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Leukapheresis ,Multiple myeloma ,Aged ,Probability ,Transplantation ,Hematology ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Hematopoietic Stem Cell Mobilization ,Nitrogen mustard ,Autotransplantation ,Surgery ,Treatment Outcome ,chemistry ,Female ,business ,medicine.drug - Abstract
In all, 451 myeloma patients, 51% previously untreated, underwent elective single autotransplantation after 200 mg/m(2) melphalan between 1985 and 2001 at the Royal Marsden Hospital. The therapy sequence was: Induction (vincristine, doxorubicin, methylprednisolone+/-cyclophosphamide), marrow or filgrastim-mobilized blood stem cell harvest, autograft, and interferon-alpha2b maintenance. A total of 27 (6%) died of transplant-related toxicity, all within 3 months. Complete or near-complete remission was seen in 59% with an overall response rate of 91%. Subsequent disease progression was seen in 285, and 17 died of unrelated causes. In all, 206 patients were alive at the last follow-up, 6 months to 17.7 years post-transplant (median 65 months); 122 without disease progression at 6 months to 17.7 years (median 58 months). The median overall (OS) and event-free (EFS) survivals were 5.9 and 2.4 years, with 10-year OS and EFS probabilities of 31.4 and 16.5%, respectively. In Cox analysis, it was seen that significantly longer OS occurred for patients who had beta-2-microglobulin3.5 mg/l (P0.0001), age60 years (P=0.001) and albuminor =35 g/l (P=0.009). EFS was also longer if beta-2-microglobulin was3.5 mg/l (P=0.0056) and patients were60 years of age (P=0.033). We conclude that with a single planned autograft, patients with myeloma have an excellent outcome.
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- 2005
29. High-dose melphalan and autotransplantation followed by post transplant maintenance chemotherapy for acute lymphoblastic leukemia in first remission
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Seema Singhal, R. L. Powles, Samar Kulkarni, Bhawna Sirohi, Jennifer Treleaven, and Jayesh Mehta
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Adult ,Male ,Melphalan ,Vincristine ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Transplantation, Autologous ,Gastroenterology ,Maintenance therapy ,Recurrence ,Acute lymphocytic leukemia ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cumulative incidence ,Aged ,Proportional Hazards Models ,Peripheral Blood Stem Cell Transplantation ,Transplantation ,Acute leukemia ,Chemotherapy ,Dose-Response Relationship, Drug ,business.industry ,Remission Induction ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Survival Analysis ,Mercaptopurine ,Surgery ,Female ,business ,medicine.drug - Abstract
A total of 65 adults with acute lymphoblastic leukemia (ALL) received 200 mg/m2 melphalan and an autograft in first remission, with a plan to receive 6-mercaptopurine (6MP), methotrexate (MTX), and vincristine–prednisone (VP) for 2 years afterwards. There was no transplant-related mortality. In all, 69% of patients received 6MP, 54% received MTX, and 49% received VP. The cumulative incidence of relapse at 5 years was 52%. The 5-year probabilities of disease-free (DFS) and overall (OS) survival were 48 and 55%. Age >30 years, >4 weeks to attain remission, and t(9;22) or t(4;11) karyotypes were adverse prognostic features. Patients with 0 (standard risk), 1 (intermediate risk), and 2–3 (high risk) adverse features had 5-year cumulative incidences of relapse of 19, 59, and 100% (P
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- 2004
30. How long after neutrophil recovery should myeloid growth factors be continued in autologous hematopoietic stem cell transplant recipients?
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Stephanie F. Williams, Amit Verma, Joanne Monreal, Jayesh Mehta, Martin S. Tallman, Seema Singhal, Steven Trifilio, J Pedicano, Jane N. Winter, and Leo I. Gordon
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Fever ,Neutrophils ,medicine.medical_treatment ,Filgrastim ,Neutropenia ,Transplantation, Autologous ,Gastroenterology ,Drug Administration Schedule ,Leukocyte Count ,Sargramostim ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,reproductive and urinary physiology ,Aged ,Retrospective Studies ,Transplantation ,Leukopenia ,business.industry ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Granulocyte-Macrophage Colony-Stimulating Factor ,Hematology ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,Autotransplantation ,Hematopoiesis ,Granulocyte colony-stimulating factor ,Surgery ,Hospitalization ,Absolute neutrophil count ,Female ,medicine.symptom ,business ,medicine.drug - Abstract
Growth factors are routinely used after autotransplantation to accelerate hematopoietic recovery, and are continued until the absolute neutrophil count (ANC) is/=0.5 x 10(9)/l on 3 consecutive days. Since ANC often increases to very high levels with this strategy, we discontinued growth factor on the first day ANC reached 0.5 x 10(9)/l in 45 patients (Study Group), and compared their subsequent ANC to 108 historic controls who received growth factor longer. While ANC on the day after reaching 0.5 x 10(9)/l was comparable between groups, ANC on the third day was significantly higher in the Control Group (2.3 vs 4.9 x 10(9)/l; P=0.0003). When compared to the first day, ANC in the Study Group was higher by a median of 140% on the third day and by 450% in the Control Group (P=0.0002). A significantly higher proportion of patients experienced a decline in ANC after the first day in the Study Group. However, only one patient in the Study Group became neutropenic transiently and ANC recovered spontaneously the next day. The incidence of fever and hospitalization were comparable. We conclude that growth factors can be discontinued after autotransplantation the day the ANC reaches 0.5 x 10(9)/l, without compromising neutrophil recovery.
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- 2004
31. Bone marrow transplantation from partially HLA-mismatched family donors for acute leukemia: single-center experience of 201 patients
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F. van Rhee, Jayesh Mehta, Adrian P. Gee, K. Y. Chiang, K. Godder, W. O'Neal, Seema Singhal, Henslee-Downey Pj, Lawrence S. Lamb, and S. DeRienzo
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Cyclophosphamide ,Graft vs Host Disease ,Gastroenterology ,Lymphocyte Depletion ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Child ,Etoposide ,Bone Marrow Transplantation ,Proportional Hazards Models ,Retrospective Studies ,Transplantation ,Acute leukemia ,Leukemia ,business.industry ,Histocompatibility Testing ,Graft Survival ,Infant ,Hematology ,Middle Aged ,Total body irradiation ,Survival Analysis ,HLA Mismatch ,Surgery ,Histocompatibility ,surgical procedures, operative ,medicine.anatomical_structure ,Child, Preschool ,Acute Disease ,Cytarabine ,Female ,Bone marrow ,business ,medicine.drug - Abstract
Between February 1993 and December 1999, 201 patients (1-59 years old, median 23) with acute leukemia (67% not in remission) underwent ex vivo T-cell-depleted (TCD) bone marrow transplants (BMT) from partially mismatched related donors (PMRD; 92% mismatched for 2-3 HLA A, B, DR antigens). Conditioning comprised total body irradiation, cyclophosphamide, cytarabine, etoposide, anti-thymocyte globulin (ATG), and methylprednisolone. Graft-versus-host disease (GVHD) prophylaxis comprised partial TCD with OKT3 (n=143) or T10B9 (n=58), steroids, ATG, and cyclosporine. The engraftment rate was 98%. The cumulative incidences of grades II-IV acute GVHD and chronic GVHD were 13 and 15%, respectively. The 5-year cumulative incidences of relapse and transplant-related mortality (TRM) were 31 and 51%, respectively. The actuarial 5-year overall survival (OS) and disease-free survival (DFS) probabilities were 19 and 18%, respectively. Patient age >15 years, active disease at transplant, donor age >25 years, and 3-antigen donor mismatch (host-versus-graft) affected the outcome adversely. The actuarial 5-year OS of four groups of patients identified based upon these risk factors was 39, 20, 13, and 0%, respectively (P
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- 2004
32. Ideal or actual body weight to calculate CD34+ cell doses for allogeneic hematopoietic stem cell transplantation?
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Leo I. Gordon, Jayesh Mehta, C Rihn, Martin S. Tallman, Jane N. Winter, Jeffrey Cilley, Seema Singhal, Stephanie F. Williams, and Joanne Monreal
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Adult ,Male ,medicine.medical_specialty ,Lymphoma ,Neutrophils ,Cd34 cells ,medicine.medical_treatment ,Antigens, CD34 ,Hematopoietic stem cell transplantation ,Body weight ,Animal science ,Cell dose ,medicine ,Humans ,Transplantation, Homologous ,Inverse correlation ,Retrospective Studies ,Transplantation ,Leukemia ,Hematopoietic cell ,business.industry ,Body Weight ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Hematopoietic Stem Cells ,Neutrophil recovery ,Surgery ,Acute Disease ,Chronic Disease ,Female ,business - Abstract
The number of CD34+ cells infused influences hematologic recovery after transplantation. Limited data suggest that cell dose should be based on ideal (IBW) rather than actual (ABW) body weight for autotransplantation, but none in allografts. We compared the correlation between recovery to 0.5 x 10(9)/l neutrophils and the CD34+ cell dose based upon ABW and IBW in 78 allograft recipients. ABW wasor =25% over IBW in 47% of patients. The median CD34+ cell dose was 5.1 x 10(6)/kg IBW and 4.4 x 10(6)/kg ABW. The time to neutrophil recovery was 8-26 days (median 12). There was a stronger inverse correlation between CD34+ cell dose/IBW and neutrophil recovery (r(2)=0.160; P0.0001) than between CD34+ cell dose/ABW and neutrophil recovery (r(2)=0.138; P=0.001). When neutrophil recovery in patients receiving3 or5 x 10(6) CD34+ cells/kg was compared to those receivingor =3 oror =5 x 10(6) CD34+ cells/kg, respectively, separately by IBW and ABW, the magnitude and significance of the differences were greater for IBW-based comparisons. These data suggest the CD34+ cell dose based on IBW is a better predictor of neutrophil recovery after allografting. Further work in a larger, more homogeneous group of patients is required to confirm this observation.
- Published
- 2003
33. Reassessing the definition of myeloid engraftment after autotransplantation: it is not necessary to see 0.5 × 109/l neutrophils on 3 consecutive days to define myeloid recovery
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Martin S. Tallman, Jayesh Mehta, MY Ali, Jane N. Winter, Yu Oyama, Seema Singhal, Leo I. Gordon, Joanne Monreal, and Stephanie F. Williams
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Myeloid ,Adolescent ,Neutrophils ,medicine.medical_treatment ,Breast Neoplasms ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,Leukocyte Count ,Terminology as Topic ,medicine ,Humans ,Myeloid Cells ,Early discharge ,Aged ,Retrospective Studies ,Transplantation ,Hematopoietic cell ,business.industry ,Graft Survival ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,Hematology ,Middle Aged ,Autotransplantation ,Surgery ,medicine.anatomical_structure ,Hematologic Neoplasms ,Absolute neutrophil count ,Female ,business - Abstract
The time to myeloid recovery after autologous hematopoietic stem cell transplantation (HSCT) is usually defined as the first of 3 consecutive days with an absolute neutrophil count (ANC) of >or=0.5 x 10(9)/l (ANC500). Universal documentation of ANC500 for 3 consecutive days, historically required to ensure robust myeloid recovery, has become difficult with a trend towards early discharge and outpatient HSCT. We studied 90 autografted patients to see how frequently ANC declined after having reached >or=0.5 x 10(9)/l. ANC500 was documented on 2 and 3 consecutive days in 14 and 63 patients, respectively. ANC increased by a median of 213% from the 1st to the 2nd day (rise in 75 and unchanged in two), and by a median of 142% from the 2nd day to the 3rd (rise in 60, unchanged in one, and decline in two; higher than the 1st day in the latter three). The increase from the 1st to the 3rd day was 13-3433% (median, 557%). Thus, in all 63 patients, no decline below ANC500 was seen, and the first day with ANC500 was also the first of 3 consecutive days with ANC500. The remaining 13 patients had repeat counts 2-7 days after the 1st day with ANC500 documenting further increase in ANC with no evidence of failed engraftment. These data show that the first day with ANC500 is also consistently the first of 3 consecutive days with ANC500 in autografted patients. Therefore, the traditional definition of myeloid engraftment should be changed to consider the first day with ANC500 as the day of engraftment without necessarily documenting ANC500 on the subsequent 1-2 days. This simple change in definition has significant implications for how data are reported to transplant registries and how peer-review organizations such as the Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT) define completeness of data.
- Published
- 2002
34. Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma
- Author
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Samar Kulkarni, R. L. Powles, Jennifer Treleaven, Seema Singhal, Jayesh Mehta, and Bhawna Sirohi
- Subjects
Adult ,Male ,Melphalan ,Oncology ,medicine.medical_specialty ,animal structures ,medicine.medical_treatment ,Transplantation, Autologous ,Disease-Free Survival ,Recurrence ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Immunopathology ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Longitudinal Studies ,neoplasms ,Multiple myeloma ,Aged ,Peripheral Blood Stem Cell Transplantation ,Transplantation ,Chemotherapy ,business.industry ,Remission Induction ,High dose melphalan ,Induction chemotherapy ,Hematology ,Middle Aged ,medicine.disease ,Autotransplantation ,Surgery ,Survival Rate ,Treatment Outcome ,Survival benefit ,Multivariate Analysis ,Female ,Multiple Myeloma ,business ,medicine.drug - Abstract
Two hundred and twenty-two myeloma patients autografted after 200 mg/m(2)melphalan were studied to examine the relationship between response to induction chemotherapy and outcome. Induction comprised cyclophosphamide, vincristine, doxorubicin and methylprednisolone (C-VAMP) every 3 weeks for one cycle beyond maximum response. 81% responded to C-VAMP (chemosensitive) with 40 complete (CR) and 139 partial (PR) remissions, and 43 did not respond (NR;50% reduction in paraprotein; primary refractory). Overall, 130 patients (59%) attained or remained in CR post-transplant; including 40% of NR, 53% of PR, and 97% of CR after C-VAMP (P0.0001). Amongst these 130 patients, the 5-year OS was independent of response to C-VAMP (NR 79%, PR 74%, CR 60%; P = 0.69). Similarly, among the 69 patients in PR post-transplant, the 5-year OS was independent of response to C-VAMP. In Cox analysis, lack of response to C-VAMP did not affect outcome significantly. These data show that lack of response to induction therapy does not automatically predict poor long-term outcome in myeloma, since a substantial proportion of these patients attain CR after autograft and enjoy extended survival. Myeloma patients should not be disqualified from an autograft based upon lack of response to induction chemotherapy.
- Published
- 2002
35. Does donor–recipient ABO incompatibility protect against relapse after allogeneic bone marrow transplantation in first remission acute myeloid leukemia?
- Author
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Diana Tait, Bhawna Sirohi, Seema Singhal, R. L. Powles, Radovan Saso, Jayesh Mehta, Samar Kulkarni, and Jennifer Treleaven
- Subjects
Adult ,Male ,Melphalan ,medicine.medical_specialty ,Myeloid ,Adolescent ,Cyclophosphamide ,Gastroenterology ,ABO Blood-Group System ,hemic and lymphatic diseases ,Internal medicine ,ABO blood group system ,parasitic diseases ,medicine ,Humans ,Transplantation, Homologous ,Bone Marrow Transplantation ,Transplantation ,business.industry ,Remission Induction ,Myeloid leukemia ,Hematology ,Middle Aged ,medicine.disease ,Tissue Donors ,Leukemia, Myeloid, Acute ,Leukemia ,surgical procedures, operative ,medicine.anatomical_structure ,Histocompatibility ,Immunology ,Female ,Bone marrow ,Erythrocyte Transfusion ,business ,medicine.drug - Abstract
It is not known if donor-recipient ABO blood group incompatibility contributes to graft-versus-leukemia after allogeneic BMT. One hundred and nineteen patients with acute myeloid leukemia in first remission underwent non-T cell-depleted marrow allografts from HLA-identical siblings after TBI and cyclophosphamide (n = 72) or melphalan (n = 47). GVHD prophylaxis comprised cyclosporine alone or cyclosporine-methotrexate. Twenty-two patients relapsed at 3-46 months (median 7): 18 of 76 patients with ABO-matched donors and four of 43 patients with ABO-mismatched donors (actuarial 5-year probabilities 33 +/- 6% vs 12 +/- 6%; P = 0.028). The incidence of acute and chronic GVHD was not affected by ABO mismatch. The following factors were studied in Cox analysis for effect on outcome: gender, age, FAB subtype, ABO mismatch, CR-transplant interval, conditioning, TBI dose, nucleated cell dose, lymphocyte recovery, acute GVHD, and chronic GVHD. Donor-recipient ABO match was the only factor independently associated with a higher risk of relapse (RR = 3.7; 95% Cl, 1.1-12.6; P = 0.04). ABO mismatch was also associated with superior overall and disease-free survivals. We conclude that ABO incompatibility may influence relapse rates and survival favorably after allogeneic BMT. It is not known if this holds true for allogeneic blood stem cell transplants.
- Published
- 2002
36. Cobe Spectra is superior to Fenwal CS 3000 Plus for collection of hematopoietic stem cells
- Author
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T. Shook, Seema Singhal, Martin S. Tallman, MY Ali, Jane N. Winter, Yu Oyama, M. Villa, Leo I. Gordon, Jayesh Mehta, R Luyun, and Stephanie F. Williams
- Subjects
Transplantation ,medicine.medical_specialty ,business.industry ,Cd34 cells ,CD34 ,Hematology ,Leukapheresis ,Hematopoietic Stem Cells ,Hematopoietic Stem Cell Mobilization ,Peripheral blood ,Blood Cell Count ,Surgery ,Blood cell ,Haematopoiesis ,medicine.anatomical_structure ,Cobe spectra ,Hematologic Neoplasms ,medicine ,Humans ,Stem cell ,business ,Nuclear medicine - Abstract
One hundred and seventy-seven stem cell apheresis procedures performed on 91 patients using the Fenwal CS 3000 Plus cell separator and 61 procedures performed on 37 patients using the Cobe Spectra cell separator were studied to compare the CD34(+) cell collection efficiencies (CE; the proportion of the total CD34(+) cell content in the blood volumes processed that is harvested) of the two machines. The absolute peripheral blood CD34(+) cell count was comparable for the two groups (P = 0.27). A strong correlation was seen between the blood CD34(+) cell count and the total number of CD34(+) cells collected for the Spectra (r(2) = 0.59; P10(-6)) and for the CS 3000 Plus (r(2) = 0.60; P10(-6)). No significant correlation emerged between the peripheral blood CD34(+) cell count and the CE of either machine. The total number of CD34(+) cells collected per procedure was comparable (P = 0.51): median 113 x 10(6) for CS 3000 Plus and median 218 x 10(6)for Spectra. CE was significantly higher with the Spectra (median 45.7%, range 9.8-98.6%) than the CS 3000 Plus (median 30.3%, range 1.7-89.3%; P0.00001). We conclude that the CD34(+) cell CE of the Spectra is superior to that of the CS 3000 Plus. Therefore, under the usual clinical conditions, Cobe Spectra should be used preferentially for peripheral blood progentor cell collection to maximize the number of hematopoietic stem cells collected.
- Published
- 2002
37. Partially mismatched related donor bone marrow transplantation as salvage for patients with AML who failed autologous stem cell transplant
- Author
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K T, Godder, J, Mehta, K Y, Chiang, S, Adams, F, van Rhee, S, Singhal, K, Higgins-Smith, W, O'Neal, S, DeRienzo, J P, Henslee-Downey, and J, Metha
- Subjects
Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Survival ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,Disease-Free Survival ,Recurrence ,medicine ,Humans ,Prospective Studies ,Treatment Failure ,Child ,Prospective cohort study ,Bone Marrow Transplantation ,Salvage Therapy ,Transplantation ,business.industry ,Histocompatibility Testing ,Hematopoietic Stem Cell Transplantation ,Immunosuppression ,Hematology ,Total body irradiation ,medicine.disease ,Tissue Donors ,Surgery ,Leukemia ,surgical procedures, operative ,medicine.anatomical_structure ,Leukemia, Myeloid ,Child, Preschool ,Acute Disease ,Female ,Bone marrow ,business ,Busulfan ,medicine.drug - Abstract
Treatment options for patients who relapse are limited and the outcome is dismal. Between August 1993 and January 1999, 17 patients, median age 26 (4-44) years, underwent T cell depleted bone marrow transplant from partially mismatched related donors (PMRD), as a salvage for AML relapsing after an autograft. The median time from auto-transplant to relapse was 7 months (1.5-24) and the interval between transplants was 10 months (3-30). All patients had active leukemia at time of transplant. Donors were siblings (n = 8), parents (n = 2), daughters (n = 4) and others (n = 3), and 82% were > or = 2 major HLA antigen mismatched with the recipient. The conditioning therapy included total body irradiation in 14 patients and was busulfan-based in three. Graft-versus-host disease (GVHD) prophylaxis consisted of partial T cell depletion along with post-transplant immunosuppression. Median day to engraftment was 16 days (12-20). Acute GVHD was seen in six patients, and chronic GVHD in four of 13 surviving beyond 100 days. Ten patients died of non-relapse causes, at 1-588 (median 77) days. Two patients relapsed at 3 and 4 months. Five patients (29%) are surviving leukemia-free 42-84 months post transplant (median 68 months). A short interval between transplants was predictive of early relapse but not mortality. Age
- Published
- 2001
38. Acute lymphoblastic leukaemia-type intensive chemotherapy to eliminate minimal residual disease after high-dose melphalan and autologous transplantation in multiple myeloma – a phase I/II feasibility and tolerance study of 17 patients
- Author
-
Jennifer Treleaven, Radovan Saso, R. L. Powles, Jayesh Mehta, N. Bhagwati, Clive Horton, Samar Kulkarni, Seema Singhal, Bhawna Sirohi, and Noopur Raje
- Subjects
Adult ,Male ,Melphalan ,medicine.medical_specialty ,Vincristine ,Neoplasm, Residual ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,Gastroenterology ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Autologous transplantation ,Multiple myeloma ,Aged ,Transplantation ,Chemotherapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Combined Modality Therapy ,Minimal residual disease ,Surgery ,Treatment Outcome ,Cytarabine ,Female ,Multiple Myeloma ,business ,medicine.drug - Abstract
Aiming to target the minimal residual disease in patients with multiple myeloma, a phase I/II single centre study was undertaken for feasibility and tolerance of intensive acute lymphoblastic leukaemia consolidation chemotherapy (ALL-IC) as part of a strategy for post-transplant consolidation targeted at pre-B cells. Seventeen newly diagnosed patients with myeloma (median age 55 years; 30-65) were initially treated with courses of infused cyclophosphamide, vincristine, adriamycin and methylprednisolone (C-VAMP) followed by melphalan 200 mg/m2(HDM) and peripheral blood stem cell rescue (PBSC). Forty-seven percent were in CR and the rest in PR after HDM. ALL-IC consisted of vincristine, daunorubicin, etoposide, cytarabine, 6-thioguanine and prednisolone given over 5 days. All patients became neutropenic (
- Published
- 2000
39. Comparison of marrow and blood cell yields from the same donors in a double-blind, randomized study of allogeneic marrow vs blood stem cell transplantation
- Author
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Bhawna Sirohi, Jayesh Mehta, R. L. Powles, A Rowland, Samar Kulkarni, Seema Singhal, S. Long, B. C. Millar, Clive Horton, Radovan Saso, Jennifer Treleaven, V. Shepherd, and S. Cabral
- Subjects
Adult ,Adolescent ,medicine.medical_treatment ,CD34 ,Antigens, CD34 ,Bone Marrow Cells ,Cell Count ,Hematopoietic stem cell transplantation ,Lenograstim ,Nuclear Family ,Andrology ,Adjuvants, Immunologic ,Double-Blind Method ,Antigens, CD ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Transplantation, Homologous ,Leukapheresis ,Progenitor cell ,Aged ,Bone Marrow Transplantation ,Transplantation ,Blood Cells ,business.industry ,Stem Cells ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Hematopoietic Stem Cell Mobilization ,Recombinant Proteins ,Tissue Donors ,Leukemia ,Hematologic Neoplasms ,Histocompatibility ,Stem cell ,business - Abstract
Forty healthy adult donors underwent marrow (BM) as well as peripheral blood (PBSC) stem cell collections for their HLA-identical adult siblings with hematologic malignancies. BM was harvested on day 1 (target 3 x 108 nucleated cells/kg, 10 microg/kg lenograstim (glycosylated G-CSF) administered on days 2-6, and a single leukapheresis performed on day 6. The blood volume processed was the higher of 200% donor blood volume or 10 liters. The total nucleated cell (TNC) yields from PBSC were 1.1- to 4.3-fold higher than BM (median 7.0 vs 3.1 x 10(8)/kg, P0.0001). Although BM contained a higher proportion of CD34+cells (1.3% vs 0.7%, P0. 0001) and a comparable proportion of CD3+ cells (median 29% vs 26%, P = 0.4), the absolute numbers of CD34+ and CD3+ cells and their subsets were several times higher in PBSC. There was a poor correlation between BM and PBSC CD34 and TNC numbers, but a significant correlation between BM and PBSC CD3 numbers. Only five of 40 BM harvests contained/=2 x 10(6) CD34+ cells/kg compared with 35 of 40 PBSC harvests (P0.0001). We conclude that the numbers of progenitor and immunocompetent cells in PBSC are several times higher than in BM. It is possible to collect adequate numbers of progenitor cells from blood after lenograstim stimulation more frequently than from marrow, and donors yielding low quantities of progenitor cells from BM usually deliver better quantities from PBSC. Bone Marrow Transplantation (2000) 25, 501-505.
- Published
- 2000
40. Melphalan/TBI is not more carcinogenic than cyclophosphamide/TBI for transplant conditioning: follow-up of 725 patients from a single centre over a period of 26 years
- Author
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J Treleaven, R Powles, A Atra, S Killick, Samar Kulkarni, Bhawna Sirohi, Simon T. Meller, Seema Singhal, Ross Pinkerton, Radovan Saso, C Horton, N Bhagawati, Diana Tait, and Jayesh Mehta
- Subjects
Adult ,Male ,Melphalan ,Pediatrics ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Cyclophosphamide ,medicine.medical_treatment ,chemistry.chemical_compound ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,Transplantation, Homologous ,Child ,Antineoplastic Agents, Alkylating ,Bone Marrow Transplantation ,Transplantation ,Chemotherapy ,Transplant Conditioning ,business.industry ,Neoplasms, Second Primary ,Hematology ,Middle Aged ,Total body irradiation ,Combined Modality Therapy ,Nitrogen mustard ,nervous system diseases ,Surgery ,Transplantation, Isogeneic ,Single centre ,surgical procedures, operative ,nervous system ,chemistry ,Child, Preschool ,Hematologic Neoplasms ,Female ,Complication ,business ,Follow-Up Studies ,medicine.drug - Abstract
As there is concern regarding the high carcinogenic potential of melphalan (Mel), 725 patients with haematological malignancies who received allogeneic (n = 714) or syngeneic (n = 11) transplants over the last 26 years were followed-up to evaluate if melphalan was more likely to result in secondary malignant neoplasms (SMNs) than cyclophosphamide (Cy). Three hundred and ninety-five were treated with Cy/TBI and 330 with Mel/TBI. Twelve patients developed non-haematological SMN. Median time to develop a SMN was 7 years (range 2-17 years). Age-adjusted rate was significantly higher than in the general population (observed 12 expected 1.2, risk 10; P0.0001). The cumulative overall risk of developing a SMN at 2, 5, 10 and 15 years post transplant was 0.4% (95% CI 0.1-2.6%), 1.7% (95% CI 0.6-4.4%), 6.4% (95% CI 2.8-10.8%) and 6.6% (95% CI 3.4-12.4%), respectively. Even though age-adjusted rates were higher than the general population melphalan/TBI was not associated with higher age-adjusted risk than Cy/TBI (increased risk 7.9 vs 11.4; P = NS). The cumulative overall risk of SMNs was not different with CY/TBI or Mel/TBI (8/393 vs 4/363; 10 year risk 4.4%, 95% CI 1.8-10.6 vs 8.4%, 95% CI 2.9-22.9; P = NS). The risk was significantly higher with use of additional cranial or cranio-spinal irradiation (17.5% vs 2.7% at 10 years; P = 0.0241). Transplants for acute lymphatic leukaemia resulted in a higher incidence of SMNs than did transplants for other diseases (ALL: 17.4%, 95% CI 6.3-42.6%; other diseases: 3.4% (95% 1.3-8.5%, P = 0.0469). The risk of SMN for patients with chronic GVHD was 8.4% (95% CI 3.7-18.7%) as compared to 3.5% (95% CI 1-11.1%) for patients without chronic GVHD (P = NS). No factor was associated with independently increased risk in multivariate analysis. Use of melphalan and TBI for transplant conditioning does not appear to be associated with higher risk of second malignant neoplasms than cyclophosphamide and TBI.
- Published
- 2000
41. Long-term outcome of adult acute leukemia patients who are alive and well 2 years after autologous blood or marrow transplantation
- Author
-
R. L. Powles, Seema Singhal, Samar Kulkarni, Jayesh Mehta, Clive Horton, and Jennifer Treleaven
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Myeloid ,Adolescent ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,Gastroenterology ,Recurrence ,Internal medicine ,Acute lymphocytic leukemia ,medicine ,Humans ,Bone Marrow Transplantation ,Transplantation ,Acute leukemia ,Leukemia ,business.industry ,Myelodysplastic syndromes ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Treatment Outcome ,medicine.anatomical_structure ,Acute Disease ,Female ,Bone marrow ,business ,Follow-Up Studies - Abstract
We studied the long-term outcome of 87 adults with acute leukemia (age 15-59 years at transplant, median 27; 44 myeloid, 42 lymphoblastic, one biphenotypic) who were alive in continuous remission 2 years after a marrow (n = 74) or blood stem cell (n = 13) autograft. Nine relapsed 25-50 months (median 38) after transplantation. Five relapses were straightforward with no karyotypic or morphologic evolution of the original disease. Four recurrences were unusual, with development of myelodysplasia (n = 3) or myeloproliferative disease (n = 1). Five patients died of relapsed disease and four are still alive. Two patients died of complications related to the transplant, and one of ischemic heart disease. Seventy-nine patients (91%) are alive in remission 24-149 months (median 67) after transplantation (75 in continuous remission and four after further therapy) with Karnofsky scores of 80-100% (median 100%). The 8-year probabilities of survival, toxic death, and relapse (from the 2-year mark) are 89%, 3% and 12%. Eleven (12%) survivors had creatinine levels of >110 micromol/l (one more than double), and 14 (16%) had bilirubin levels of >17 mmol/l (one more than double) at the last follow-up. None of the following factors was found to be predictive for survival, non-relapse death, or relapse from the 2-year mark in multivariate analysis: age, sex, type of leukemia, disease stage, diagnosis, conditioning, origin of cells, and nucleated cell dose. We conclude that adult patients with acute leukemia who are alive and well 2 years following an autograft have a high probability of being cured, and the incidence of long-term liver and kidney dysfunction measured by serum bilirubin and creatinine is low.
- Published
- 1999
42. Recombinant tissue plasminogen activator (rtPA) for the treatment of hepatic veno-occlusive disease (VOD)
- Author
-
Jayesh Mehta, Seema Singhal, Samar Kulkarni, Diana Tait, P Mateos, R. L. Powles, M Rodriguez, Jennifer Treleaven, A Lafuente, and Radovan Saso
- Subjects
Adult ,medicine.medical_specialty ,Hepatic veno-occlusive disease ,Bilirubin ,medicine.medical_treatment ,Hepatic Veno-Occlusive Disease ,Hematopoietic stem cell transplantation ,Gastroenterology ,chemistry.chemical_compound ,Bolus (medicine) ,Internal medicine ,Humans ,Medicine ,Transplantation ,Chemotherapy ,Creatinine ,business.industry ,T-plasminogen activator ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Surgery ,chemistry ,Tissue Plasminogen Activator ,business ,Complication - Abstract
Seventeen patients who developed hepatic veno-occlusive disease (VOD) following hematopoietic stem cell transplantation were treated with recombinant tissue plasminogen activator (rtPA) with or without heparin. rtPA was started a median of 13 days post transplant (range 4-35). All patients received rtPA at a dose of 10 mg/day as a starting dose, and 12 patients also received heparin (1500 U bolus; then 100 U/kg/day as a continuous i.v. infusion). The median number of days of rtPA therapy was 2.5 (1-12). The median total serum bilirubin level was 116 mmol/l (range 63-194) at the beginning of treatment. Six patients showed a response to rtPA treatment (29%). It was observed that by day 2 of rtPA therapy, bilirubin levels in responders showed a downwards trend as compared to those in nonresponders. In all except one patient this response was observed after two doses of rtPA. Seven out of the 11 non-responders had a past history of liver dysfunction, compared with none of the responders. There were no differences between the two groups in terms of day of onset of liver dysfunction, manifestations of disease, maximum bilirubin and creatinine levels, and day of commencing treatment. No patient experienced severe hemorrhagic complications during therapy. Four responders survived for more than 100 days compared to none of the non-responders. Probability of survival was 33% at day 100. It is difficult to unequivocally establish the role of rtPA in the treatment of VOD. The importance of bilirubin levels on days 2 or 3 of therapy in predicting outcome should be established, as should the optimum dose of rtPA and optimum duration of therapy.
- Published
- 1999
43. Reimmunization after blood or marrow stem cell transplantation
- Author
-
Seema Singhal and Jayesh Mehta
- Subjects
Transplantation ,Allogeneic transplantation ,business.industry ,medicine.medical_treatment ,Hematopoietic Stem Cell Transplantation ,Immunization, Secondary ,Hematology ,Hematopoietic stem cell transplantation ,Antibodies, Viral ,Active immunization ,Vaccination ,surgical procedures, operative ,medicine.anatomical_structure ,Immunization ,Immunity ,Immunology ,medicine ,Humans ,Bone marrow ,business ,Immunization Schedule ,Bone Marrow Transplantation - Abstract
Protective immunity to diseases preventable by routine vaccination is lost over time following allogeneic and autologous blood and marrow transplantation. Adoptive transfer of immunity from donors to recipients after allogeneic transplantation is not sufficient to prevent this decline. Systematic reimmunization is necessary at appropriate time intervals following transplantation to re-establish immunity. Response to vaccination depends upon the type of transplant, the source of cells, the immune status of the patient, and the vaccine being used. While inactivated or subunit vaccines are safe in all transplant recipients, live vaccines are generally contraindicated. Reimmunization practices vary widely amongst transplant centers. This comprehensive review summarizes published data on post-transplant vaccination, and based upon these, suggests guidelines which may be used as a framework for development of reimmunization protocols.
- Published
- 1999
44. Red cell fragmentation (schistocytosis) after bone marrow transplantation
- Author
-
Jennifer Treleaven, R. L. Powles, Radovan Saso, Jayesh Mehta, Seema Singhal, A Zomas, and H Mackay
- Subjects
Adult ,Hemolytic anemia ,medicine.medical_specialty ,Thrombotic microangiopathy ,Adolescent ,Thrombotic thrombocytopenic purpura ,Erythrocytes, Abnormal ,Hemolysis ,Transplantation, Autologous ,Gastroenterology ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Autologous transplantation ,Fragmentation (cell biology) ,Child ,Bone Marrow Transplantation ,Transplantation ,Red Cell ,business.industry ,Incidence ,Hematology ,Middle Aged ,medicine.disease ,Schistocyte ,Surgery ,Hematologic Neoplasms ,business - Abstract
Red cell fragmentation is often the earliest sign of thrombotic microangiopathy. Days +14, +28 and +42 blood films from 58 allograft and 32 autograft recipients were reviewed blind to determine the incidence and severity of schistocytosis (the number of fragmented red cells per 1000 red cells expressed as a percentage). Schistocytosis was graded as mild (1%), moderate (1-1.9%) or severe (or =2%). Schistocytes were seen in 99% of day 14 films (0.1-3.0%, median 0.4%), 97% of day 28 films (0.1-3.2%, median 0.4%), and 98% of day 42 films (0.1-4.3%, median 0.5%). Nine patients (10%) had severe fragmentation and 20 patients (22%) had moderate fragmentation at some time or the other. The difference in the extent of fragmentation between the days was not significant. Allogeneic BMT was associated with more extensive fragmentation than autologous transplantation on day 28 (P = 0.008) and day 42 (P = 0.02). Age, conditioning regimen and diagnosis had no influence. None of the patients followed-up for 6 months after transplant developed full-blown thrombotic microangiopathy. The occasional patient showing mild clinical and laboratory features of hemolysis responded well to adjustment of fluid balance and cyclosporine dose where applicable. Our data indicate that mild red cell fragmentation is a common morphologic finding after transplantation with no clinical significance in the absence of other clinical and laboratory findings suggestive of thrombotic microangiopathy, although patients with moderate or severe fragmentation should be monitored closely.
- Published
- 1998
45. Outcome assessment of a population-based group of 195 unselected myeloma patients under 70 years of age offered intensive treatment
- Author
-
Martin Gore, Noopur Raje, B. C. Millar, R. L. Powles, Jennifer Treleaven, Sarah Milan, C. Viner, Samar Kulkarni, Seema Singhal, David Cunningham, V. Shepherd, and Jayesh Mehta
- Subjects
Adult ,Male ,Melphalan ,medicine.medical_specialty ,Cyclophosphamide ,medicine.medical_treatment ,Population ,chemistry.chemical_compound ,Maintenance therapy ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Outcome Assessment, Health Care ,medicine ,Humans ,Autologous transplantation ,education ,Referral and Consultation ,Aged ,Bone Marrow Transplantation ,Aged, 80 and over ,Transplantation ,Chemotherapy ,education.field_of_study ,business.industry ,Remission Induction ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Interferon-alpha ,Hematology ,Middle Aged ,Survival Analysis ,Nitrogen mustard ,Blood Cell Count ,Surgery ,Verapamil ,chemistry ,Population Surveillance ,Female ,Neoplasm Recurrence, Local ,Multiple Myeloma ,business ,Busulfan ,medicine.drug - Abstract
A single centre series of 195 consecutive newly diagnosed untreated myeloma patients under 70 years, seen between September 1986 and March 1994, were analysed to assess the impact of current intensive treatment methods upon remission rate, response rate and subsequent outcome. They were predominantly an unselected population based group of patients (other than by age) that could be used by purchasers of health care as a model for outcome assessment. All patients were scheduled to receive a care plan which included a sequential package of treatment consisting initially of courses of infusional chemotherapy using vincristine, adriamycin and methyl prednisolone (VAMP) and 90 of these also received cyclophosphamide (C-VAMP). Thirty-eight patients received verapamil in addition to C-VAMP(V-C-VAMP). After VAMP all patients were planned to receive high-dose treatment with melphalan and an autograft (marrow or blood) and 112 received this treatment; a further 29 patients received modified high-dose treatment with melphalan alone (23) or busulfan (6) and 54 (28%) did not proceed to high-dose treatment because of refusal, resistant disease, poor performance or treatment-related death. The patients who received melphalan or busulfan alone instead of high-dose melphalan/autografts did so because of increasing age (P = 0.001) and a raised creatinine (P = 0.05). The complete remission rate was 53% for the whole group and 74% for those receiving high-dose melphalan and an autograft. From July 1988, the sequential therapy package included continuous three times weekly interferon (IFN) after high-dose treatment as maintenance therapy, initially as part of a controlled randomised trial and then for all suitable patients. Fifty-seven patients received IFN. The median overall survival (OS) and progression-free survival (PFS) from first treatment for the whole group of 195 patients is 4.5 years and 25 months, respectively. The 112 patients receiving the melphalan autografts fared significantly better than the rest of the patients with OS and PFS (from high-dose treatment) of 6.6 years and 27 months, respectively (P < 0.005), and the 57 patients also receiving ifn have a os yet to reach a median at 8 years and a pfs of 44 months, significantly better than non ifn high-dose patients (P < 0.0036). however, although we showed benefit for selected patients in studies and trials (particularly with ifn) during the 8-year period of the series, this did not translate into overall pfs benefit in our study for unselected cohorts of patients for 1986–1988 (64 patients) 1989–1992 (100 patients) and 1992–1994 (31 patients) in spite of progressive increases in the proportion of patients receiving ifn (respectively 6, 35 and 58%). this is likely to be due to the dilution of benefit to specific patients by the overall number of patients involved. outcome data from unselected patients are now expected by purchasers and presented in this way, help qualify the activity impact of advances made from research trials for the treatment of population-based cancer problems.
- Published
- 1997
46. Amphotericin B lipid complex (ABLC) for the treatment of confirmed or presumed fungal infections in immunocompromised patients with hematologic malignancies
- Author
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Seema Singhal, Jennie Treleaven, C. Evans, Patrick Chu, Unell Riley, Jayesh Mehta, Stephen M. Kelsey, Adrian C. Newland, Ray Powles, and Dena L. Hazel
- Subjects
Adult ,Male ,medicine.medical_specialty ,Antifungal Agents ,Adolescent ,medicine.medical_treatment ,Aspergillosis ,Transplantation, Autologous ,Gastroenterology ,Nephrotoxicity ,Immunocompromised Host ,Amphotericin B ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Mycosis ,Aged ,Bone Marrow Transplantation ,Transplantation ,Chemotherapy ,business.industry ,Phosphatidylglycerols ,Immunosuppression ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Drug Combinations ,Mycoses ,Hematologic Neoplasms ,Concomitant ,Phosphatidylcholines ,Female ,business ,medicine.drug - Abstract
Sixty-four adult patients (median age 43) with hematologic malignancies who were immunocompromised after allogeneic (n = 23) or autologous (n = 9) blood/marrow transplantation, or chemotherapy (n = 32) received 68 courses of amphotericin B lipid complex (ABLC, Abelcet) at the daily dose of 5 mg/kg for presumed (n = 52) or proven (n = 16) fungal infection. The major indications for ABLC were failure of previous antifungal therapy and/or renal dysfunction. Fifty-three treatment courses in 49 patients comprising 4-58 doses (median 10) were considered evaluable. Fourteen courses administered for confirmed infections resulted in nine complete and one partial responses, and four failures (71% response). Thirty-nine empiric courses resulted in 18 complete and six partial responses, and 14 failures (64% response). The overall response rate was 66%. Five of seven evaluable patients with aspergillus pneumonia responded. Response rates were comparable for chemotherapy, autograft and allograft recipients. The change in serum creatinine from the beginning to the end of therapy was -284 to +277 mumol/l (median +24). The creatinine doubled during seven evaluable courses of therapy, five of which were associated with concomitant nephrotoxic therapy. Nephrotoxicity was comparable for transplant and chemotherapy patients. Renal dysfunction necessitated discontinuation of ABLC in only four patients. These data suggest that ABLC is effective in presumed or confirmed fungal infections in immunocompromised patients after transplantation or chemotherapy.
- Published
- 1997
47. Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially?
- Author
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J, Mehta, L I, Gordon, M S, Tallman, J N, Winter, A M, Evens, A O, Evens, O, Frankfurt, S F, Williams, D, Grinblatt, L, Kaminer, R, Meagher, and S, Singhal
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Affect (psychology) ,Donor age ,Disease-Free Survival ,Recurrence ,Risk Factors ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Aged ,Retrospective Studies ,Transplantation ,Analysis of Variance ,Hematology ,Hematopoietic cell ,business.industry ,Siblings ,Graft Survival ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Reduced intensity ,Middle Aged ,Survival Rate ,Treatment Outcome ,Hematologic Neoplasms ,Immunology ,Female ,Stem cell ,business - Abstract
Sixty three patients aged 27-66 years (median 52) were allografted from HLA-matched sibling (n=47), 10 of 10 allele-matched unrelated (n=19), or one-antigen/allele-mismatched (n=7) donors aged 24-69 years (median 46) after a conditioning regimen comprising 100 mg/m(2) melphalan. Cyclophosphamide (50 mg/kg) was also administered to patients who had not been autografted previously. Cyclosporine or tacrolimus, and mycophenolate mofetil were administered to prevent graft-versus-host disease (GVHD). The 2-year cumulative incidences of relapse and TRM were 55 and 24% respectively, and 2-year probabilities of overall survival (OS) and disease-free survival (DFS) were 36 and 21%, respectively. Poor performance status, donor age45 years and elevated lactate dehydrogenase (LDH) increased the risk of treatment-related mortality (TRM), refractory disease and donor age45 years increased the risk of relapse, and OS and DFS were adversely influenced by refractory disease, poor performance status, increased LDH, and donor age45 years. Our data suggest that younger donor age is associated with better outcome after sub-myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies due to lower TRM and relapse. This finding raises the question of whether a young 10-allele-matched unrelated donor is superior to an older matched sibling donor in patients where the clinical situation permits a choice between such donors.
- Published
- 2006
48. Reduced-dose rasburicase (recombinant xanthine oxidase) in adult cancer patients with hyperuricemia
- Author
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Steven Trifilio, Jayesh Mehta, J. Pi, Andrew M. Evens, Martin S. Tallman, K. Masino, K. Rashid, Seema Singhal, M. Fishman, and Leo I. Gordon
- Subjects
Adult ,Male ,medicine.medical_specialty ,Urate Oxidase ,medicine.medical_treatment ,Urology ,Allopurinol ,Hyperuricemia ,chemistry.chemical_compound ,Internal medicine ,Neoplasms ,Rasburicase ,Medicine ,Humans ,Xanthine oxidase ,Aged ,Retrospective Studies ,Aged, 80 and over ,Transplantation ,Chemotherapy ,Creatinine ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Uric Acid ,Tumor lysis syndrome ,Endocrinology ,chemistry ,Uric acid ,Female ,business ,Tumor Lysis Syndrome ,medicine.drug - Abstract
Recombinant urate oxidase (rasburicase) lowers uric acid levels rapidly to very low levels at the labeled dose of 0.15-0.2 mg/kg daily for 5 days. Our past experience showed that a lower dose (3 mg) lowered uric acid levels sufficiently in most patients. A retrospective review was conducted to determine the effect of a fixed 3 mg dose of rasburicase in 43 adult patients with cancer undergoing hematopoietic stem cell transplantation or receiving chemotherapy who had elevated or rising uric acid levels (6.4-16.8 mg/dl; median 9.6). Six patients received a second dose of rasburicase (3 mg in four patients and 1.5 mg in two patients) 24 h later. Patients received allopurinol, adequate hydration, as well as other supportive therapy as required. Uric acid levels declined by 6-95% (median 43%) within the first 24 h after rasburicase administration, and levels at 48 h were 9-91% (median 65%) lower than the baseline levels. Serum creatinine changed byor =10% in 21 patients, increased by10% in four patients and decreased by10% in 18 patients. No significant renal dysfunction developed in any of the patients. We conclude that rasburicase is effective in lowering uric acid levels at a fixed dose of 3 mg, which is much lower than the recommended dose.
- Published
- 2006
49. Ideal rather than actual body weight should be used to calculate cell dose in allogeneic hematopoietic stem cell transplantation
- Author
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S, Singhal, L I, Gordon, M S, Tallman, J N, Winter, A M, Evens, A O, Evens, O, Frankfurt, S F, Williams, D, Grinblatt, L, Kaminer, R, Meagher, and J, Mehta
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Urology ,Antigens, CD34 ,Cell Count ,Hematopoietic stem cell transplantation ,Body weight ,Thinness ,Cell dose ,Antigens, CD ,medicine ,Humans ,Transplantation, Homologous ,Survival analysis ,Preparative Regimen ,Aged ,Transplantation ,business.industry ,Body Weight ,Hematology ,Middle Aged ,Overweight ,Survival Analysis ,Surgery ,Treatment Outcome ,Allogeneic hsct ,Tissue and Organ Harvesting ,Female ,Underweight ,medicine.symptom ,business ,Stem Cell Transplantation - Abstract
Whether the CD34+ and CD3+ cell doses in allogeneic HSCT should be estimated using actual (ABW) or ideal (IBW) body weight has never been definitively determined. We have shown that CD34+ cell doses based upon IBW are better predictive of engraftment after autologous and allogeneic HSCT. Sixty-three patients undergoing reduced-intensity HSCT after a uniform preparative regimen were evaluated to determine the effect of cell dose. ABW and IBW were 45-147 kg (median 79) and 52-85 kg (median 67) respectively. The ABW-IBW difference was -24% to +133% (median +16%); nine patients were >5% underweight and 41 were >5% overweight. The CD34+ cell dose (10(6)/kg) was 1.4-11.8 (median 5) by IBW and 1.2-9.3 (median 4.5) by ABW. The CD3+ cell dose (10(8)/kg) was 0.9-14.9 (median 3) by IBW and 0.7-19.7 (median 2.7) by ABW. While CD34+ and CD3+ cell doses based upon IBW were found to affect transplant-related mortality, and disease-free and overall survival significantly, those based on ABW were either not predictive of outcome or the differences were of borderline significance. We suggest using IBW rather than ABW to calculate cell doses for HSCT; for statistical analyses and for clinical practice if a specific cell dose is being targeted.
- Published
- 2006
50. Sensitivity of secondary acute myeloid leukemia relapsing after allogeneic bone marrow transplantation to immunotherapy with interferon-α2b
- Author
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Seema Singhal, R. L. Powles, Jennifer Treleaven, and Jayesh Mehta
- Subjects
Adult ,medicine.medical_specialty ,Myeloid ,Graft vs Host Disease ,Alpha interferon ,Interferon alpha-2 ,Gastroenterology ,Recurrence ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Secondary Acute Myeloid Leukemia ,Interferon alfa ,Bone Marrow Transplantation ,Transplantation ,Acute leukemia ,business.industry ,Interferon-alpha ,Myeloid leukemia ,Hematology ,medicine.disease ,Recombinant Proteins ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,Immunology ,Female ,business ,medicine.drug - Abstract
A patient with acute myeloid leukemia secondary to therapy of choriocarcinoma underwent T cell non-depleted allogeneic bone marrow transplantation from an unrelated donor in first untreated relapse. Persistent/relapsed leukemia 4 months after transplantation did not respond to cessation of cyclosporine. Due to logistic difficulties in obtaining donor leukocytes, she was treated with interleukin-2 and interferon-alpha 2b. Although the interleukin could be administered for a short period only, the interferon was continued for 4 months. Interferon was stopped when limited chronic graft-versus-host disease developed, but was followed by extramedullary and early marrow relapse. Reinstitution of interferon resulted in the development of scleroderma-like extensive chronic GVHD and remission. Interferon was given for 5 months. GVHD improved slowly with treatment, but scleroderma-like changes still persist. The patient is alive with no evidence of disease and a Karnofsky score of 90% 41 months after relapse and 26 months after stopping cyclosporine. We conclude that cytokines alone may occasionally result in a durable response of acute leukemia relapsing after allografting, and should be considered in patients with a low tumor burden if it is difficult to obtain donor cells.
- Published
- 1997
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