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ABSTRACT: Most reports addressing pulmonary complications (PCs) in hematopoietic stem cell transplant (HSCT) recipients have focused on allogeneics. This study describes the PCs, their risk factors, and the impact on mortality in autologous recipients.
We reviewed the medical records of 1,243 adult autologous HSCT recipients. We collected pretransplant and posttransplant data and data on PC after transplant and long-term mortality.
Four hundred eighty-seven PC developed in 343 patients (27.6%): 173 infectious (13.9%), 127 noninfectious (10.2%), and 43 both infectious and noninfectious (3.5%). Bacterial, fungal, and viral pneumonias were the most common infectious complications. The main noninfectious complications were acute pulmonary edema (APE) (59 [4.7%]), diffuse alveolar hemorrhage (DAH) (26 [2.1%]), peri-engraftment respiratory distress syndrome (PERDS) (31 [2.5%]), and idiopathic pneumonia syndrome (IPS) (12 [1.0%]). Independent factors associated with PC included diffusing capacity of lung for carbon monoxide and indications for transplant. Factors associated with mortality included sex, history of pulmonary disease, disease status at the time of transplant, FVC, Karnofsky score, and underlying diagnosis. A Cox proportional hazards regression model with separate time-dependent predictors for the first 1 month, 1 to 2 months, 2 to 6 months, and 6 or more months showed an association with mortality at hazard ratios (HRs) of 32.39, 10.13, 4.29, and 0.98, respectively, compared with persons without PC.
More than 25% of autologous HSCT recipients develop PCs within 1 year of transplant. Most of the complications are infections. The most common noninfectious complications are APE, DAH, PERDS, and IPS. PCs increase the risk of death, with HR as high as 32.
Chest 07/2011; 141(2):442-50. · 5.25 Impact Factor
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ABSTRACT: CYP2B6, CYP2C19, ABCC4, and SOD2 have been implicated in adverse drug reactions and survival after cyclophosphamide (CPA) treatment. 110 BMT patients who received high dose CPA treatment were genotyped for variants in these genes and the results were correlated with toxicity and relapse. CYP2B6 genotype significantly influenced overall toxicity suggesting active CYP2B6 alleles led to higher rates of overall toxicity. The p.R487C deficiency allele was significantly associated with a lower rate of overall toxicity and a higher rate of relapse. SOD2 rs4880 V16A polymorphism was associated with significantly less CPA-related overall toxicity and significantly lower relapse rates by Kaplan-Meier analysis although the SOD2 finding regarding relapse was not significant when evaluated by the cumulative incidence function.
Leukemia research 07/2011; 36(1):59-66. · 2.36 Impact Factor
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Sherif S Farag,
Kati Maharry,
Mei-Jie Zhang,
Waleska S Pérez,
Stephen L George,
Krzysztof Mrózek,
John DiPersio,
Donald W Bunjes,
Guido Marcucci,
Maria R Baer, [......],
Hillard M Lazarus, Mark R Litzow,
David I Marks,
Olle Ringdén,
David A Rizzieri,
Robert Soiffer,
Richard A Larson,
Martin S Tallman,
Clara D Bloomfield,
Daniel J Weisdorf
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ABSTRACT: We compared the outcomes of patients age 60-70 years with acute myelogenous leukemia receiving reduced-intensity allogeneic hematopoietic cell transplantation (HCT) in first remission (CR1) reported to the Center for International Blood and Marrow Research (n = 94) with the outcomes in patients treated with induction and postremission chemotherapy on Cancer and Leukemia Group B protocols (n = 96). All patients included had been in CR1 for at least 4 months. The HCT recipients were slightly younger than the chemotherapy patients (median age, 63 years vs 65 years; P < .001), but there were no significant between-group differences in the proportion with therapy-related leukemia or in different cytogenetic risk groups. Time from diagnosis to CR1 was longer for the HCT recipients (median, 44 days vs 38 days; P = .031). Allogeneic HCT was associated with significantly lower risk of relapse (32% vs 81% at 3 years; P < .001), higher nonrelapse mortality (36% vs 4% at 3 years; P < .001), and longer leukemia-free survival (32% vs 15% at 3 years; P = .001). Although overall survival was longer for HCT recipients, the difference was not statistically significant (37% vs 25% at 3 years; P = .08). Our findings suggest that reduced-intensity conditioning allogeneic HCT in patients age 60-70 with acute myelogenous leukemia in CR1 reduces relapse and improves leukemia-free survival. Strategies that reduce nonrelapse mortality may yield significant improvements in overall survival.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2011; 17(12):1796-803. · 3.15 Impact Factor
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ABSTRACT: Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder of which approximately 300 cases have been reported in the literature. Patients with RTS often present early in life with skeletal and dental abnormalities, short stature, juvenile cataracts, and a characteristic poikilodermal rash. They are at increased risk for the development of osteosarcoma that usually presents by the second decade of life. The genetic defects underlying RTS are truncating mutations in RECQL4, a gene involved with chromosomal stability. Several cases of primary hematological malignancies have been reported in RTS, but it is unclear whether patients with RTS are at higher risk to develop either primary or secondary hematological malignancies. We report a patient with RTS who presented to our clinic at the age of 7, subsequently developed multifocal and recurrent osteosarcoma that was followed by the development of a myelodysplastic syndrome with subsequent progression to acute myeloid leukemia.
European Journal Of Haematology 03/2011; 86(6):536-40. · 2.61 Impact Factor
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Hugo F Fernandez,
Zhuoxin Sun, Mark R Litzow,
Selina M Luger,
Elisabeth M Paietta,
Janis Racevskis,
Gordon Dewald,
Rhett P Ketterling,
Jacob M Rowe,
Hillard M Lazarus,
Martin S Tallman
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ABSTRACT: We report the results of a prospective, randomized phase 3 trial evaluating the use of gemtuzumab ozogamicin (GO) in an intensive consolidation approach in 657 patients 17-60 years of age. Patients in first complete remission (CR1) after cytarabine and standard- or high-dose daunorubicin induction received 2 cycles of consolidation with high-dose cytarabine followed by peripheral blood progenitor cell collection. The 352 patients who entered consolidation were randomized to receive GO (n = 132) or not (n = 138) and then proceeded to autologous hematopoietic cell transplantation (HCT). GO was given to 67 patients. Median follow-up was 50.9 months. Results of the intention-to-treat analysis demonstrated a 4-year disease-free survival (DFS) of 33.6% versus 35.9% (P = .54) and an overall survival (OS) of 41.3% versus 41.9% (P = .52) for those randomized to receive GO versus no GO, respectively. Patients with favorable- and intermediate-risk acute myeloid leukemia (AML) treated with high-dose daunorubicin and autologous HCT had 4-year DFS rates of 60% and 40% and OS rates of 80% and 49.3%, respectively. For younger AML patients in CR1, autologous HCT should be considered in favorable- and intermediate-cytogenetic risk patients who do not have an allogeneic donor. The addition of a single dose of GO in this setting did not improve outcomes.
Blood 03/2011; 117(20):5306-13. · 9.90 Impact Factor
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John T Horan,
Brent R Logan,
Manza-A Agovi-Johnson,
Hillard M Lazarus,
Andrea A Bacigalupo,
Karen K Ballen,
Christopher N Bredeson,
Matthew H Carabasi,
Vikas Gupta,
Gregory A Hale,
Hanna Jean Khoury,
Mark B Juckett, Mark R Litzow,
Rodrigo Martino,
Philip L McCarthy,
Franklin O Smith,
J Douglas Rizzo,
Marcelo C Pasquini
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ABSTRACT: Transplantation-related mortality (TRM) is a major barrier to the success of allogeneic hematopoietic cell transplantation (HCT).
We assessed changes in the incidence of TRM and overall survival from 1985 through 2004 in 5,972 patients younger than age 50 years who received myeloablative conditioning and HCT for acute myeloid leukemia (AML) in first complete remission (CR1) or second complete remission (CR2).
Among HLA-matched sibling donor transplantation recipients, the relative risks (RRs) for TRM were 0.5 and 0.3 for 2000 to 2004 compared with those for 1985 to 1989 in patients in CR1 and CR2, respectively (P < .001). The RRs for all causes of mortality in the latter period were 0.73 (P = .001) and 0.60 (P = .005) for the CR1 and CR2 groups, respectively. Among unrelated donor transplantation recipients, the RRs for TRM were 0.73 (P = .095) and 0.58 (P < .001) for 2000 to 2004 compared with those in 1990 to 1994 in the CR1 and CR2 groups, respectively. Reductions in mortality were observed in the CR2 group (RR, 0.74; P = .03) but not in the CR1 group.
Our results suggest that innovations in transplantation care since the 1980s and 1990s have reduced the risk of TRM in patients undergoing allogeneic HCT for AML and that this reduction has been accompanied by improvements in overall survival.
Journal of Clinical Oncology 01/2011; 29(7):805-13. · 18.37 Impact Factor
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Mark Levis,
Farhad Ravandi,
Eunice S Wang,
Maria R Baer,
Alexander Perl,
Steven Coutre,
Harry Erba,
Robert K Stuart,
Michele Baccarani,
Larry D Cripe, [......],
Gunnar Juliusson, Mark R Litzow,
Stephen Petersdorf,
Miguel Sanz,
Hagop M Kantarjian,
Takashi Sato,
Lothar Tremmel,
Debra M Bensen-Kennedy,
Donald Small,
B Douglas Smith
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ABSTRACT: In a randomized trial of therapy for FMS-like tyrosine kinase-3 (FLT3) mutant acute myeloid leukemia in first relapse, 224 patients received chemotherapy alone or followed by 80 mg of the FLT3 inhibitor lestaurtinib twice daily. Endpoints included complete remission or complete remission with incomplete platelet recovery (CR/CRp), overall survival, safety, and tolerability. Correlative studies included pharmacokinetics and analysis of in vivo FLT3 inhibition. There were 29 patients with CR/CRp in the lestaurtinib arm and 23 in the control arm (26% vs 21%; P = .35), and no difference in overall survival between the 2 arms. There was evidence of toxicity in the lestaurtinib-treated patients, particularly those with plasma levels in excess of 20 μM. In the lestaurtinib arm, FLT3 inhibition was highly correlated with remission rate, but target inhibition on day 15 was achieved in only 58% of patients receiving lestaurtinib. Given that such a small proportion of patients on this trial achieved sustained FLT3 inhibition in vivo, any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients with FLT3 mutant acute myeloid leukemia in first relapse. This study is registered at www.clinicaltrials.gov as #NCT00079482.
Blood 01/2011; 117(12):3294-301. · 9.90 Impact Factor
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ABSTRACT: Zosuquidar, which modulates P-glycoprotein (P-gp) with minimal delay of anthracycline clearance, may reverse P-gp-mediated resistance in acute myeloid leukemia without increased toxicity. A total of 449 adults older than 60 years with acute myeloid leukemia or high-risk myelodysplastic syndrome enrolled in a randomized placebo-controlled double-blind trial (Eastern Cooperative Oncology Group 3999). Overall survival was compared between patients receiving conventional-dose cytarabine and daunorubicin and either zosuquidar (550 mg; 212 patients) or placebo (221 patients). Median and 2-year overall survival values were 7.2 months and 20% on zosuquidar and 9.4 months and 23% on placebo, respectively (P = .281). Remission rate was 51.9% on zosuquidar and 48.9% on placebo. All cause mortality to day 42 was not different (zosuquidar 22.2% vs placebo 16.3%; P = .158). In vitro modulation of P-gp activity by zosuquidar and expression of P-gp, multidrug resistance-related protein 1, lung resistance protein, and breast cancer resistance protein, were comparable in the 2 arms. Poor-risk cytogenetics were more common in P-gp(+) patients. P-gp expression and cytogenetics were correlated, though independent prognostic factors. We conclude that zosuquidar did not improve outcome in older acute myeloid leukemia, in part, because of the presence P-gp independent mechanisms of resistance. This trial is registered at www.clinicaltrials.gov as #NCT00046930.
Blood 11/2010; 116(20):4077-85. · 9.90 Impact Factor
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ABSTRACT: Patients with newly diagnosed acute myeloid leukemia (AML) often have residual leukemia in the bone marrow 10 to 14 days after the start of induction therapy. Some cooperative groups administer a second cycle of similar induction therapy on Day 14 if there is residual leukemia. It is a common perception that the presence of residual leukemia at that point predicts a worse prognosis irrespective of the therapy received. The objective of this study was to determine whether patients who required a second cycle of induction (given on or about Day 14) to achieve complete remission (CR) had a worse prognosis than patients who achieved CR after only 1 cycle, because a worse prognosis may alter postremission therapy.
Patients who were enrolled on 6 consecutive studies for AML that were conducted by the Eastern Cooperative Oncology Group (ECOG) between 1983 to 1993 received induction therapy. If residual leukemia was present in the bone marrow on the Day 14 after the start of induction, then patients were to receive a second cycle of identical induction therapy. All patients who achieved CR after 1 or 2 cycles received the identical postremission therapy.
In each of the 6 ECOG studies, the long-term outcome was similar for patients who required 1 or 2 cycles of induction therapy to achieve CR, and their outcome was independent of other prognostic variables, such as age or karyotype.
The presence of residual leukemia in bone marrow 10 to 14 days after induction therapy did not predict a worse prognosis if patients received second, similar cycle of induction therapy and achieved CR.
Cancer 11/2010; 116(21):5012-21. · 4.77 Impact Factor
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Willis H Navarro,
Manza-A Agovi,
Brent R Logan,
Karen Ballen,
Brian J Bolwell,
Haydar Frangoul,
Vikas Gupta,
Theresa Hahn,
Vincent T Ho,
Mark Juckett,
Hillard M Lazarus, Mark R Litzow,
Jane L Liesveld,
Jan S Moreb,
David I Marks,
Philip L McCarthy,
Marcelo C Pasquini,
J Douglas Rizzo
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ABSTRACT: The incidence of excessive adiposity is increasing worldwide, and is associated with numerous adverse health outcomes. We compared outcomes by body mass index (BMI) for adult patients with acute myelogenous leukemia (AML) who underwent autologous (auto, n = 373), related donor (RD, n = 2041), or unrelated donor (URD, n = 1801) allogeneic myeloablative hematopoietic cell transplantation (HCT) using bone marrow or peripheral blood stem cells reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2004. Four weight groups by BMI (kg/m(2)) were defined: underweight <18 kg/m(2); normal 18-25 kg/m(2); overweight >25-30 kg/m(2); and obese >30 kg/m(2). Multivariable analysis referenced to the normal weight group showed an increased risk of death for underweight patients in the RD group (relative risk [RR], 1.92; 95% confidence interval [CI], 1.28-2.89; P = .002), but not in the URD group. There were no other differences in outcomes among the other weight groups within the other HCT groups. Overweight and obese patients enjoyed a modest decrease in relapse incidence, although this did not translate into a survival benefit. Small numbers of patients limit the ability to better characterize the adverse outcomes seen in the underweight RD but not the underweight URD allogeneic HCT patients. Obesity alone should not be considered a barrier to HCT.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2010; 16(10):1442-50. · 3.15 Impact Factor
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Morie A Gertz,
Martha Q Lacy,
Angela Dispenzieri,
Suzanne R Hayman,
Shaji K Kumar,
David Dingli,
Stephen M Ansell,
Dennis A Gastineau,
David J Inwards,
Patrick B Johnston, Mark R Litzow,
Ivana N M Micallef,
Luis F Porrata,
Nelson Leung,
William J Hogan,
Francis K Buadi
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ABSTRACT: High-dose chemotherapy for the management of immunoglobulin light chain amyloidosis remains an effective and viable treatment technique for selected patients with this disorder. We reviewed the medical records of 434 patients uniformly treated with high-dose chemotherapy and autologous stem cell transplant at Mayo Clinic, Rochester, Minnesota, between 8 March 1996 and 13 April 2010. Outcomes, engraftment, and predictors of early mortality were reviewed. Median survival has not been reached for the patients with a complete response, is 107 months for those with a partial response, and is 32 months for patients with no response (p < 0.001). The only predictor of survival was cardiac stage (p < 0.001). The hematologic response rate is predictive for organ response rates. Both hematologic and organ responses are associated with improved survival.
Leukemia & lymphoma 10/2010; 51(12):2181-7. · 2.40 Impact Factor
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Michel Duval,
John P Klein,
Wensheng He,
Jean-Yves Cahn,
Mitchell Cairo,
Bruce M Camitta,
Rammurti Kamble,
Edward Copelan,
Marcos de Lima,
Vikas Gupta,
Armand Keating,
Hillard M Lazarus, Mark R Litzow,
David I Marks,
Richard T Maziarz,
David A Rizzieri,
Gary Schiller,
Kirk R Schultz,
Martin S Tallman,
Daniel Weisdorf
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ABSTRACT: Patients with acute leukemia refractory to induction or reinduction chemotherapy have poor prognoses if they do not undergo hematopoietic stem-cell transplantation (HSCT). However, HSCT when a patient is not in complete remission (CR) is of uncertain benefit. We hypothesized that pretransplantation variables may define subgroups that have a better prognosis.
Overall, 2,255 patients who underwent transplantation for acute leukemia in relapse or with primary induction failure after myeloablative conditioning regimen between 1995 and 2004 were reported to the Center for International Blood and Marrow Transplant Research. The median follow-up of survivors was 61 months. We performed multivariate analysis of pretransplantation variables and developed a predictive scoring system for survival.
The 3-year overall survival (OS) rates were 19% for acute myeloid leukemia (AML) and 16% for acute lymphoblastic leukemia (ALL). For AML, five adverse pretransplantation variables significantly influenced survival: first CR duration less than 6 months, circulating blasts, donor other than HLA-identical sibling, Karnofsky or Lansky score less than 90, and poor-risk cytogenetics. For ALL, survival was worse with the following: first refractory or second or greater relapse, > or = 25% marrow blasts, cytomegalovirus-seropositive donor, and age of 10 years or older. Patients with AML who had a predictive score of 0 had 42% OS at 3 years, whereas OS was 6% for a score > or = 3. Patients with ALL who had a score of 0 or 1 had 46% 3-year OS but only 10% OS rate for a score > or = 3.
Pretransplantation variables delineate subgroups with different outcomes. HSCT during relapse can achieve long-term survival in selected patients with acute leukemia.
Journal of Clinical Oncology 08/2010; 28(23):3730-8. · 18.37 Impact Factor
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Angela Dispenzieri,
Gregory A Wiseman,
Martha Q Lacy,
Suzanne R Hayman,
Shaji K Kumar,
Francis Buadi,
David Dingli,
Krista M Laumann,
Jake Allred,
Susan M Geyer, Mark R Litzow,
Dennis A Gastineau,
David J Inwards,
Ivana N Micallef,
Stephen M Ansell,
Luis Porrata,
Michelle A Elliott,
Patrick B Johnston,
William J Hogan,
Morie A Gertz
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ABSTRACT: Multiple myeloma (MM) remains an incurable illness affecting nearly 20,000 individuals in the United States per year. High-dose melphalan (HDM) with autologous hematopoietic stem cell support (ASCT) is one of the mainstays of therapy for younger patients, but little advancement has been made with regards to conditioning regimens. We opted to combine (153)Samarium ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP), a radiopharmaceutical approved for the palliation of pain caused by metastatic bone lesions, with HDM and ASCT in a Phase II study. Individualized doses of (153)Sm were based on dosimetry and were calculated to deliver 40 Gy to the bone marrow. The therapeutic dose of (153)Sm-EDTMP was followed by HDM and ASCT. Forty-six patients with newly diagnosed or relapsed disease were treated. Study patients were compared to 102 patients contemporaneously treated with HDM and ASCT. Fifty-nine percent of study patients achieved a very good partial response (VGPR) or better. With a median follow-up of 7.1 years, the median overall survival and progression free survival (PFS) from study registration was 6.2 years (95% CI 4.6-7.5 years) and 1.5 years (1.1-2.2 years), respectively, which compared favorably to contemporaneously treated non-study patients. Addition of high-dose (153)Sm-EDTMP to melphalan conditioning appears to be safe, well tolerated, and worthy of further study in the context of novel agents and in the Phase III setting.
American Journal of Hematology 06/2010; 85(6):409-13. · 4.67 Impact Factor
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Mark R Litzow,
Sergey Tarima,
Waleska S Pérez,
Brian J Bolwell,
Mitchell S Cairo,
Bruce M Camitta,
Corey S Cutler,
Marcos de Lima,
John F Dipersio,
Robert Peter Gale, [......],
Selina Luger,
David I Marks,
Richard T Maziarz,
Philip L McCarthy,
Marcelo C Pasquini,
Gordon L Phillips,
J Douglas Rizzo,
Jorge Sierra,
Martin S Tallman,
Daniel J Weisdorf
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ABSTRACT: Therapy-related myelodysplastic syndromes (t-MDSs) and acute myeloid leukemia (t-AML) have a poor prognosis with conventional therapy. Encouraging results are reported after allogeneic transplantation. We analyzed outcomes in 868 persons with t-AML (n = 545) or t-MDS (n = 323) receiving allogeneic transplants from 1990 to 2004. A myeloablative regimen was used for conditioning in 77%. Treatment-related mortality (TRM) and relapse were 41% (95% confidence interval [CI], 38-44) and 27% (24-30) at 1 year and 48% (44-51) and 31% (28-34) at 5 years, respectively. Disease-free (DFS) and overall survival (OS) were 32% (95% CI, 29-36) and 37% (34-41) at 1 year and 21% (18-24) and 22% (19-26) at 5 years, respectively. In multivariate analysis, 4 risk factors had adverse impacts on DFS and OS: (1) age older than 35 years; (2) poor-risk cytogenetics; (3) t-AML not in remission or advanced t-MDS; and (4) donor other than an HLA-identical sibling or a partially or well-matched unrelated donor. Five-year survival for subjects with none, 1, 2, 3, or 4 of these risk factors was 50% (95% CI, 38-61), 26% (20-31), 21% (16-26), 10% (5-15), and 4% (0-16), respectively (P < .001). These data permit a more precise prediction of outcome and identify subjects most likely to benefit from allogeneic transplantation.
Blood 03/2010; 115(9):1850-7. · 9.90 Impact Factor
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American Journal of Hematology 02/2010; 85(2):129-30. · 4.67 Impact Factor
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Jeffrey Schriber,
Manza-A Agovi,
Vincent Ho,
Karen K Ballen,
Andrea Bacigalupo,
Hillard M Lazarus,
Christopher N Bredeson,
Vikas Gupta,
Richard T Maziarz,
Gregory A Hale, Mark R Litzow,
Brent Logan,
Martin Bornhauser,
Roger H Giller,
Luis Isola,
David I Marks,
J Douglas Rizzo,
Marcelo C Pasquini
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ABSTRACT: Failure to engraft donor cells is a devastating complication after allogeneic hematopoietic cell transplantation (HCT). We describe the results of 122 patients reported to the National Marrow Donor Program between 1990 and 2005, who received a second unrelated donor HCT after failing to achieve an absolute neutrophil count of >or=500/microL without recurrent disease. Patients were transplanted for leukemia (n = 83), myelodysplastic disorders (n = 16), severe aplastic anemia (n = 20), and other diseases (n = 3). The median age was 29 years. Twenty-four patients received second grafts from a different unrelated donor. Among 98 patients who received a second graft from the same donor, 28 received products that were previously collected and cryopreserved for the first transplantation. One-year overall survival (OS) after second transplant was 11%, with 10 patients alive at last follow-up. We observed no differences between patients who received grafts from the same or different donors, or in those who received fresh or cryopreserved product. The outcomes after a second allogeneic HCT for primary graft failure are dismal. Identifying risk factors for primary graft failure can decrease the incidence of this complication. Further studies are needed to test whether early recognition and hastened procurement of alternative grafts can improve transplant outcomes for primary graft failure.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2010; 16(8):1099-106. · 3.15 Impact Factor
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Blood 10/2009; 114(16):3502-3. · 9.90 Impact Factor
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David I Marks,
Elisabeth M Paietta,
Anthony V Moorman,
Susan M Richards,
Georgina Buck,
Gordon DeWald,
Adolfo Ferrando,
Adele K Fielding,
Anthony H Goldstone,
Rhett P Ketterling, Mark R Litzow,
Selina M Luger,
Andrew K McMillan,
Marc R Mansour,
Jacob M Rowe,
Martin S Tallman,
Hillard M Lazarus
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ABSTRACT: The biology and outcome of adult T-cell acute lymphoblastic leukemia are poorly understood. We present here the clinical and biologic features of 356 patients treated uniformly on the prospective trial (UKALL XII/ECOG 2993) with the aim of describing the outcome and identifying prognostic factors. Complete remission was obtained in 94% of patients, and 48% survived 5 years. Positivity of blasts for CD1a and lack of expression of CD13 were associated with better survival (P = .01 and < .001, respectively). NOTCH1 and CDKN2A mutations were seen in 61% and 42% of those tested. Complex cytogenetic abnormalities were associated with poorer survival (19% vs 51% at 5 years, P = .006). Central nervous system involvement at diagnosis did not affect survival (47% vs 48%, P = not significant). For 99 patients randomized between autograft and chemotherapy, 5-year survival was 51% in each arm. Patients with a matched sibling donor had superior 5-year survival to those without donors (61% vs 46%, chi(2), P = .02); this was the result of less relapse (25% vs 51% at 5 years, P < .001). Only 8 of 123 relapsed patients survive. This study provides a baseline for trials of new drugs, such as nelarabine, and may allow risk-adapted therapy in patients with poor-prognosis T-cell ALL.
Blood 10/2009; 114(25):5136-45. · 9.90 Impact Factor
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Karen K Ballen,
Smriti Shrestha,
Kathleen A Sobocinski,
Mei-Jie Zhang,
Asad Bashey,
Brian J Bolwell,
Francisco Cervantes,
Steven M Devine,
Robert Peter Gale,
Vikas Gupta, [......],
David I Marks,
Richard T Maziarz,
Philip L McCarthy,
Gary Schiller,
Harry C Schouten,
Vivek Roy,
Peter H Wiernik,
Mary M Horowitz,
Sergio A Giralt,
Mukta Arora
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ABSTRACT: Myelofibrosis is a myeloproliferative disorder incurable with conventional strategies. Several small series have reported long-term disease-free survival (DSF) after allogeneic hematopoietic cell transplantation (HCT). In this study, we analyze the outcomes of 289 patients receiving allogeneic transplantation for primary myelofibrosis between 1989 and 2002, from the database of the Center for International Bone Marrow Transplant Research (CIBMTR). The median age was 47 years (range: 18-73 years). Donors were HLA identical siblings in 162 patients, unrelated individuals in 101 patients, and HLA nonidentical family members in 26 patients. Patients were treated with a variety of conditioning regimens and graft-versus-host disease (GVHD) prophylaxis regimens. Splenectomy was performed in 65 patients prior to transplantation. The 100-day treatment-related mortality was 18% for HLA identical sibling transplants, 35% for unrelated transplants, and 19% for transplants from alternative related donors. Corresponding 5-year overall survival (OS) rates were 37%, 30%, and 40%, respectively. DFS rates were 33%, 27%, and 22%, respectively. DFS for patients receiving reduced-intensity transplants was comparable: 39% for HLA identical sibling donors and 17% for unrelated donors at 3 years. In this large retrospective series, allogeneic transplantation for myelofibrosis resulted in long-term relapse-free survival (RFS) in about one-third of patients.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2009; 16(3):358-67. · 3.15 Impact Factor
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Mark R Litzow,
Megan Othus,
Larry D Cripe,
Steven D Gore,
Hillard M Lazarus,
Sandra J Lee,
John M Bennett,
Elisabeth M Paietta,
Gordon W Dewald,
Jacob M Rowe,
Martin S Tallman
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ABSTRACT: The treatment of relapsed acute myeloid leukaemia (AML) remains unsatisfactory. We conducted a phase II randomized trial where patients received intermediate-dose cytarabine for 4 d followed by gemtuzumab ozogamicin on day 5 (Arm A), or combined with liposomal daunorubicin for 3 d (Arm B), or cytarabine given for 5 d combined with cyclophosphamide for 3 d and topotecan by continuous infusion for 5 d (Arm C). Eligible patients had primary refractory AML, a first relapse after a remission of <1 year, or a second or greater relapse. The primary objective of this trial was attainment of a conventional complete remission (CR) or a CR without platelet recovery (CRp) in at least 40% of patients. The CR/CRp rates for the 82 eligible patients were 3/26 (12%) in Arm A, 2/29 (7%) in Arm B, and 1/27 (4%) in Arm C. No patients who had relapsed within 6 months of initial CR or who had suffered multiple relapses responded. More than 95% of patients subsequently died of AML. No unexpected toxicities were encountered. We conclude that none of these three regimens were effective enough in the treatment of high-risk relapsed or refractory AML to warrant further study. This trial was registered at http://www.clinicaltrials.gov as #NCT00005962.
British Journal of Haematology 10/2009; 148(2):217-25. · 4.94 Impact Factor
