S Singhal

Northwestern University, Evanston, IL, United States

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Publications (161)777.75 Total impact

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    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 in <8 or >16 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.
    Bone marrow transplantation 10/2008; 43(4):301-5. · 3.00 Impact Factor
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    J Mehta, S Singhal
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    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.
    Bone Marrow Transplantation 08/2008; 42 Suppl 1:S28-S34. · 3.54 Impact Factor
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    ABSTRACT: A total of 100 adults with ALL in first CR received melphalan (110 mg/m(2)) with TBI followed by autologous marrow (n=35) or single-agent melphalan (200 mg/m(2)) followed by autologous blood stem cells (n=65). After adequate hematologic recovery, maintenance chemotherapy with 6-mercaptopurine, methotrexate and vincristine-prednisone was administered for 2 years. Six patients, all TBI recipients (P=0.001), died of toxicity. In total 70 patients received 6-mercaptopurine, 53 received methotrexate and 40 received vincristine-prednisone. The cumulative incidence of relapse at 7 years was 45%. The 7-year probabilities of disease-free survival (DFS) and overall survival were 45 and 48%. Age 30 years, >4 weeks to attain remission, and karyotypes t(4;11) and t(9;22) were associated with adverse outcome. Patients with 0 (standard risk), 1 (intermediate risk), and 2-3 (high risk) adverse features had 7-year cumulative incidences of relapse of 19, 53 and 82% (P<0.0001), and 7-year DFS probabilities of 73, 36 and 7% (P<0.0001). The 7-year probabilities of DFS for patients receiving 0, 1, 2 and 3 maintenance chemotherapy agents were 15, 29, 58 and 61% (P<0.0001). Maintenance chemotherapy intensity was an independent determinant of outcome in Cox analysis. Maintenance chemotherapy after autotransplantation reduces relapse and improves outcome in adult patients with ALL.
    Bone Marrow Transplantation 05/2008; 42(2):105-12. · 3.54 Impact Factor
  • Biology of Blood and Marrow Transplantation - BIOL BLOOD MARROW TRANSPLANT. 01/2008; 14(2):133-133.
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    J Mehta, S Singhal
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    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.
    Bone Marrow Transplantation 01/2008; 40(12):1101-14. · 3.54 Impact Factor
  • Biology of Blood and Marrow Transplantation - BIOL BLOOD MARROW TRANSPLANT. 01/2008; 14(2):115-116.
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    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 were <0.2, <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 of < or =2 microg/ml and none among the 24 with levels of >2 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.
    Bone Marrow Transplantation 09/2007; 40(5):451-6. · 3.54 Impact Factor
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    ABSTRACT: The standard approach to treatment of relapsed/refractory Hodgkin's lymphoma (HL) is high-dose chemotherapy conditioning followed by autologous hematopoietic stem-cell transplantation (aHSCT). We report the results of a prospective phase I/II clinical trial of accelerated hyperfractionated total lymphoid irradiation (TLI) immediately followed by high-dose chemotherapy for relapsed/refractory HL. Forty-eight patients underwent aHSCT with either sequential TLI/chemotherapy (n = 32) or chemotherapy-alone conditioning (n = 16), based on prior radiation exposure. The first 22 patients enrolled on trial received escalating doses of etoposide (1600-2100 mg/m(2)) with high-dose carboplatin and cyclophosphamide. No dose-limiting toxicity was seen and TLI/chemotherapy was well tolerated. The 5-year event-free survival (EFS) estimate for all patients was 44% with overall survival (OS) of 48%. Five-year EFS and OS for the TLI/chemotherapy group was 63% and 61%, respectively, compared with 6% and 27%, respectively, for the chemotherapy-alone group (P < 0.0001 and P = 0.04, respectively). Patients with primary induction failure HL who received TLI/chemotherapy had 5-year EFS and OS rate of 83%. The 100-day treatment-related mortality was 4.2% and two secondary cancers were seen. Significant factors predicting survival by multivariate analysis included TLI/chemotherapy conditioning and B symptoms at relapse. Sequential TLI/chemotherapy conditioning for relapsed/refractory HL is safe and associated with excellent long-term survival rates.
    Annals of Oncology 04/2007; 18(4):679-88. · 7.38 Impact Factor
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    J Mehta, S Singhal
    Bone Marrow Transplantation 03/2007; 39(4):243-4. · 3.54 Impact Factor
  • Biology of Blood and Marrow Transplantation - BIOL BLOOD MARROW TRANSPLANT. 01/2007; 13(2):153-154.
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    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 age >45 years and elevated lactate dehydrogenase (LDH) increased the risk of treatment-related mortality (TRM), refractory disease and donor age >45 years increased the risk of relapse, and OS and DFS were adversely influenced by refractory disease, poor performance status, increased LDH, and donor age >45 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.
    Bone Marrow Transplantation 07/2006; 38(2):95-100. · 3.54 Impact Factor
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    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 by < or =10% in 21 patients, increased by >10% in four patients and decreased by >10% 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.
    Bone Marrow Transplantation 06/2006; 37(11):997-1001. · 3.54 Impact Factor
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    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.
    Bone Marrow Transplantation 03/2006; 37(6):553-7. · 3.54 Impact Factor
  • Biology of Blood and Marrow Transplantation - BIOL BLOOD MARROW TRANSPLANT. 01/2006; 12(2):170-170.
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    ABSTRACT: Healthy stem cell donors start leukapheresis 4-5 days after starting G-CSF based on the peripheral blood CD34+ cell count (PBCD34). Data from 137 harvests (68 donors) were analyzed to determine correlation between pre-apheresis leukocytes (11.0-94.8x10(9)/l; median 38.8) and platelets (49-374x10(9)/l; median 180), and PBCD34 (3-276/microl; median 40). PBCD34 correlated positively with leukocytes (r=0.48; P<0.0001) and platelets (r=0.40; P<0.0001). When pre-apheresis leukocytes were >or=25 and platelets were >or=100, PBCD34 and CD34+ collection were 5-276/microl (median 57) and 0.5-27.6x10(6)/kg (median 4.7), respectively; significantly higher than PBCD34 of 3-74/microl (median 17) and CD34+ collection of 0.2-8.9 x 10(6)/kg (median 2.2) when leukocytes were <25 and/or platelets were <100. With leukocytes >or=25 and platelets >or=100, PBCD34 was low (<20/microl) 8% of the time, compared to 57% of the time with leukocytes <25 and/or platelets <100 (P<0.0001). Our data suggest that it is not always necessary to measure PBCD34 to guide leukapheresis in healthy donors because pre-apheresis leukocytes and platelets >or=25 and >or=100, respectively, are associated with excellent mobilization. When blood counts do not meet these criteria, PBCD34 should be determined prior to initiation of apheresis.
    Bone Marrow Transplantation 11/2005; 36(8):663-6. · 3.54 Impact Factor
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    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-microglobulin <3.5 mg/l (P<0.0001), age <60 years (P=0.001) and albumin > or =35 g/l (P=0.009). EFS was also longer if beta-2-microglobulin was <3.5 mg/l (P=0.0056) and patients were <60 years of age (P=0.033). We conclude that with a single planned autograft, patients with myeloma have an excellent outcome.
    Bone Marrow Transplantation 08/2005; 36(1):19-24. · 3.54 Impact Factor
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    ABSTRACT: A total of 415 leukaphereses in 201 patients stimulated with growth factor (GF; n = 119) or chemotherapy-GF (n = 296) were studied to determine CD34+ cell collection efficiency (CE). The pre-apheresis leukocyte count was 1-93 x 10(9)/l (median 20), and peripheral blood CD34 count (PBCD34) was 1-1104/microl (median 19). The total number of CD34+ cells collected was 4-6531 x 10(6) (median 151); corresponding to 0.1-111.4 x 10(6) (median 2.3) per kg. There was strong correlation between PBCD34 and the number of CD34+ cells collected (r = 0.9; P < 0.0001). CE was 7-145% (median 46). On multiple regression analysis, a higher leukocyte count (P < 0.0001) was the most important predictor of lower CE. CE with leukocytes < 20 was 7-145% (median 53%) compared to 10-132% (median 40%) with leukocyte > or = 20 (P < 0.0001). In all, 61% of the apheresis procedures performed after chemotherapy-GF occurred when leukocytes were < 20 compared to 21% of those performed after GF alone (P < 0.0001). We conclude that mobilizing patients with the combination of chemotherapy and GF rather than GF alone leads to leukapheresis being performed when the leukocyte count is low -- in a range that results in optimum CD34+ cell CE. Autologous stem cells should be mobilized with chemotherapy-GF rather than GF alone whenever possible.
    Bone Marrow Transplantation 03/2005; 35(3):243-6. · 3.54 Impact Factor
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    ABSTRACT: The role of autologous stem cell transplantation in adult patients with acute myeloid leukaemia (AML) in first remission is unclear, yet it has become standard treatment for myeloma and this paper explores whether the source of transplanted stem cells may explain this paradox. In total, 57 patients from the Royal Marsden Hospital who received an unpurged bone marrow transplant (ABMT) were matched with 114 patients from the EBMT registry who had undergone peripheral blood stem cell transplantation (PBSCT). Patients were matched for karyotype, FAB type, remission-autograft interval and age. In the PBSCT group, haematopoietic recovery was significantly faster and nonrelapse mortality at 4 years was significantly lower (13 vs 1%, P=0.04). The relapse rate and overall survival at 4 years (20 vs 31% and 77 vs 63%) were also better with PBSCT, although the differences were not statistically significant. Autografting should be reassessed in a randomised trial for first remission AML patients using peripheral blood as a source of stem cells rather than bone marrow.
    Bone Marrow Transplantation 07/2004; 33(12):1209-14. · 3.54 Impact Factor
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    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<0.0001), and 5-year probabilities of DFS of 80, 41, and 0% (P<0.0001). The 5-year probabilities of DFS for patients receiving 0, 1, 2, and 3 maintenance therapy agents were 19, 40, 51, and 70% (P=0.0097). Maintenance therapy intensity was an independent determinant of outcome in Cox analysis. These data show that a high-dose melphalan-based autograft is safe and could be widely applicable in ALL in first remission, and that maintenance chemotherapy very likely contributes to improved outcome of autografted ALL patients.
    Bone Marrow Transplantation 06/2004; 33(11):1107-14. · 3.54 Impact Factor
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    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.
    Bone Marrow Transplantation 04/2004; 33(7):715-9. · 3.54 Impact Factor

Publication Stats

4k Citations
777.75 Total Impact Points

Institutions

  • 2001–2008
    • Northwestern University
      • • Division of Hematology/Oncology
      • • Feinberg School of Medicine
      Evanston, IL, United States
  • 2006–2007
    • Northwestern Memorial Hospital
      • Department of Pharmacy
      Chicago, IL, United States
  • 2005
    • Nottinghamshire Healthcare NHS Trust
      Nottigham, England, United Kingdom
  • 2002
    • Ann & Robert H. Lurie Children's Hospital of Chicago
      Chicago, Illinois, United States
  • 2000–2002
    • Institute of Cancer Research
      Londinium, England, United Kingdom
  • 1999–2001
    • University of South Carolina
      • School of Medicine
      Columbia, SC, United States
  • 1997–2001
    • The Royal Marsden NHS Foundation Trust
      Londinium, England, United Kingdom
  • 1997–1999
    • University of Arkansas for Medical Sciences
      Little Rock, Arkansas, United States
  • 1997–1998
    • University of Arkansas at Little Rock
      Little Rock, Arkansas, United States
  • 1991–1993
    • Bombay Hospital & Medical Research Centre
      Mumbai, Mahārāshtra, India