Publications by authors named "Indira Sahdev"

15 Publications

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Timing of Alemtuzumab With Respect to Day of Bone Marrow Infusion and its Effects Upon Engraftment and Graft-Versus-Host Disease in Patients With Sickle Cell Disease: A Single-Institutional Study.

J Pediatr Hematol Oncol 2020 11;42(8):e718-e722

Division of Pediatric Hematology/Oncology and Stem Cell Transplantation, Department of Pediatrics, Cohen Children's Medical Center of New York, New Hyde Park, NY.

The possible impact of "late" alemtuzumab (administered on days -10 to -8) versus "early" alemtuzumab (-19 to -17) with respect to engraftment and acute/chronic graft-versus-host disease (GvHD) in a group of 25 pediatric patients with sickle cell disease undergoing bone marrow transplantation following conditioning with alemtuzumab, fludarabine, and melphalan is reported. The first 9 patients received "late" alemtuzumab followed by bone marrow transplantation from HLA-matched sibling donors. The next 16 patients undergoing matched sibling transplants received "early" alemtuzumab. In the "late" group, 1 patient (11%) developed acute GvHD. Six patients (67%) achieved sustained engraftment. Three patients (33%) experienced graft rejection, leading to termination of enrollment of patients on this regimen. In the "early" alemtuzumab group, acute and chronic GvHD developed in 43% and 25% patients, respectively. None of the patients experienced graft rejection in this group of patients. Three patients developed stable mixed chimerism and 13 patients demonstrated 100% donor chimerism at 1 year post-transplant and beyond. These results suggest a benefit with respect to engraftment of administering "early" versus "late" alemtuzumab in this reduced-intensity conditioning regimen, however, with the possible cost of an increase in acute, and possibly chronic GvHD.
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http://dx.doi.org/10.1097/MPH.0000000000001930DOI Listing
November 2020

Higher Risks of Toxicity and Incomplete Recovery in 13- to 17-Year-Old Females after Marrow Donation: RDSafe Peds Results.

Biol Blood Marrow Transplant 2019 05 31;25(5):955-964. Epub 2018 Dec 31.

Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

Although donation of bone marrow (BM) or peripheral blood stem cells (PBSCs) from children to family members undergoing allogeneic transplantation are well-established procedures, studies detailing levels of pain, symptoms, and long-term recovery are lacking. To address this lack, we prospectively enrolled 294 donors age <18 years at 25 pediatric transplantation centers in North America, assessing them predonation, peridonation, and at 1 month, 6 months, and 1 year postdonation. We noted that 71% of children reported pain and 59% reported other symptoms peridonation, with resolution to 14% and 12% at 1 month postdonation. Both older age (age 13 to 17 years versus younger) and female sex were associated with higher levels of pain peridonation, with the highest rates in older females (57% with grade 2-4 pain and 17% with grade 3-4 pain). Multivariate analyses showed a 4-fold increase in risk for older females compared with males age <13 years (P <.001). At 1 year, 11% of 13- to 17-year-old females reported grade 2-4 pain, compared with 3% of males age 13 to 17 years, 0% of females age <13 years, and 1% of males age <13 years (P = .01). Males and females age 13 to 17 years failed to return to predonation pain levels at 1 year 22% and 23% of the time, respectively, compared with 3% and 10% in males and females age <13 years (P = .002). Our data show that females age 13 to 17 years are at increased risk of grade 2-4 pain at 1 year and >20% of females and males age 13 to 17 years do not return to baseline pain levels by 1 year after BM donation. Studies aimed at decreasing symptoms and improving recovery in older children are warranted.
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http://dx.doi.org/10.1016/j.bbmt.2018.12.765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511296PMC
May 2019

Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study.

Biol Blood Marrow Transplant 2019 04 10;25(4):699-711. Epub 2018 Nov 10.

Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota; National Marrow Donor Program/Be the Match, Minneapolis, Minnesota.

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34 level before apheresis compared with younger RDs (age > 60, 59 × 10/L; age 41 to 60, 81 × 10/L; age 18 to 40, 121 × 10/L; P < .001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P < .001) and higher collection volumes (52% versus 32% > 24 L, P < .001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia <50 × 10/L (26% and 57% after 2 and 3days of collection, respectively). RDs aged 18 to 40 had a higher risk of grades 2 to 4 pain and symptoms pericollection, but donors over age 40 had more persistent pain at 1, 6, and 12 months (odds ratio [OR], 1.7; P = 0.02) and a higher rate of nonrecovery to predonation levels (OR, 1.7; P = .01). Donors reporting comorbidities increased significantly with age, and those with comorbidities that would have led to deferral by National Marrow Donor Program unrelated donor standards had an increased risk for persistent grades 2 to 4 pain (OR, 2.41; P < .001) and failure to recover to predonation baseline for other symptoms (OR, 2.34; P = .004). This information should be used in counseling RDs regarding risk and can assist in developing practice approaches aimed at improving the RD experience for high-risk individuals.
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http://dx.doi.org/10.1016/j.bbmt.2018.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453753PMC
April 2019

Related peripheral blood stem cell donors experience more severe symptoms and less complete recovery at one year compared to unrelated donors.

Haematologica 2019 04 31;104(4):844-854. Epub 2018 Oct 31.

Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI.

Unlike unrelated donor registries, transplant centers lack uniform approaches to related donor assessment and deferral. To test whether related donors are at increased risk for donation-related toxicities, we conducted a prospective observational trial of 11,942 related and unrelated donors aged 18-60 years. Bone marrow (BM) was collected at 37 transplant and 78 National Marrow Donor Program centers, and peripheral blood stem cells (PBSC) were collected at 42 transplant and 87 unrelated donor centers in North America. Possible presence of medical comorbidities was verified prior to donation, and standardized pain and toxicity measures were assessed pre-donation, peri-donation, and one year following. Multivariate analyses showed similar experiences for BM collection in related and unrelated donors; however, related stem cell donors had increased risk of moderate [odds ratios (ORs) 1.42; <0.001] and severe (OR 8.91; <0.001) pain and toxicities (OR 1.84; <0.001) with collection. Related stem cell donors were at increased risk of persistent toxicities (OR 1.56; =0.021) and non-recovery from pain (OR 1.42; =0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; <0.001) and non-recovery from toxicities (OR 3.71; <0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; <0.001) and non-recovery from toxicities (OR 3.71; <0.001) at one year. Related donors reporting grade ≥2 pain had significant decreases in Health-Related Quality of Life (HR-QoL) scores at one month and one year post donation (=0.004). In conclusion, related PBSC donors with comorbidities are at increased risk for pain, toxicity, and non-recovery at one year after donation. Risk profiles described in this study should be used for donor education, planning studies to improve the related donor experience, and decisions regarding donor deferral. Registered at .
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http://dx.doi.org/10.3324/haematol.2018.200121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442962PMC
April 2019

A Multicenter Study of Bacterial Blood Stream Infections in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients: The Role of Acute Gastrointestinal Graft-versus-Host Disease.

Biol Blood Marrow Transplant 2017 Apr 16;23(4):642-647. Epub 2017 Jan 16.

Department of Pediatrics, UCSF Benioff Children's Hospital, San Francisco, California.

Blood stream infections (BSI) caused by enteric organisms are associated with a particularly high mortality rate in allogeneic hematopoietic cell transplantation (alloHCT) recipients. We conducted a retrospective multicenter study aiming to analyze the risk factors associated with antibiotic resistance and impact of BSI on transplantation-related mortality (TRM) in children after alloHCT. During the study period from 2004 to 2014, 395 children (mean age, 9.4 years) with at least 1 BSI were included. The incidences of resistant gram-negative rods were 20.7% to piperacillin-tazobactam, 10.9% to cefepime, 21% to ceftazidime, 11.4% to levofloxacin, and 8.16% to meropenem. Thirty-eight percent of Enterococcus spp. isolates were resistant to vancomycin. More than 1 episode of BSI was associated with significant increase in the risk of resistance to piperacillin-tazobactam, cefepime, and vancomycin. On multivariate analysis of risk factors for TRM, achievement of neutrophil engraftment by day 30 was associated with lower TRM (P = .002). However, infection with an antibiotic-resistant organism was not associated with TRM. Development of enteric bacterial BSI after the onset of acute gastrointestinal graft-versus-host disease (GVHD) was the strongest predictor of TRM (hazard ratio, 4.786; 95% confidence interval, 2.833 to 8.087; P < .001). In patients with acute gastrointestinal GVHD who subsequently developed enteric bacterial BSI, the incidence of 1-year TRM was 33.4% (SE = 7%), compared with 15.3% (SE = 2%) for those without acute gastrointestinal GVHD (P = .004). Primary prevention of a first episode of BSI is arguably the most important intervention to decrease antibiotic resistance. It is also imperative that we develop strategies to maintain gastrointestinal health, especially in patients with gastrointestinal GVHD, in an effort to prevent subsequent enteric bacterial BSI and improve survival.
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http://dx.doi.org/10.1016/j.bbmt.2017.01.073DOI Listing
April 2017

Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies.

Am J Hematol 2015 Dec 6;90(12):1093-8. Epub 2015 Oct 6.

Department of Pediatric, Washington University School of Medicine, St. Louis, Missouri.

Fifty-two children with symptomatic sickle cell disease sickle cell disease (SCD) (N = 43) or transfusion-dependent thalassemia (N = 9) received matched sibling donor marrow (46), marrow and cord product (5), or cord blood (1) allografts following reduced intensity conditioning (RIC) with alemtuzumab, fludarabine, and melphalan between March 2003 and May 2014*. The Kaplan-Meier probabilities of overall and event-free survival at a median of 3.42 (range, 0.75-11.83) years were 94.2% and 92.3% for the group, 93% and 90.7% for SCD, and 100% and 100% for thalassemia, respectively. Treatment-related mortality (all related to graft versus host disease, GVHD) was noted in three (5.7%) recipients, all 17-18 years of age. Acute and chronic GVHD was noted in 23% and 13%, respectively, with 81% of recipients off immunosuppression by 1 year. Graft rejection was limited to the single umbilical cord blood recipient who had prompt autologous hematopoietic recovery. Fourteen (27%) had mixed chimerism at 1 year and beyond; all had discontinued immunosuppression between 4 and 12 months from transplant with no subsequent consequence on GVHD or rejection. Infectious complications included predominantly bacteremia (48% were staphylococcus) and CMV reactivation (43%) necessitating preemptive therapy. Lymphocyte recovery beyond 6 months was associated with subsidence of infectious complications. All patients who engrafted were transfusion independent; no strokes or pulmonary complications of SCD were noted, and pain symptoms subsided within 6 months posttransplant. These findings support using RIC for patients with hemoglobinopathy undergoing matched sibling marrow transplantation (*www.Clinical Trials.gov: NCT00920972, NCT01050855, NCT02435901).
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http://dx.doi.org/10.1002/ajh.24183DOI Listing
December 2015

Alemtuzumab Pharmacokinetics in Hematopoietic Stem Cell Transplants for Nonmalignant Genetic Diseases.

Biol Blood Marrow Transplant 2015 Jul 9;21(7):1337. Epub 2015 May 9.

Steven and Alexandra Cohen Children's Medical Center of New York, New York, New York.

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http://dx.doi.org/10.1016/j.bbmt.2015.04.013DOI Listing
July 2015

Outcomes after hematopoietic stem cell transplantation for children with I-cell disease.

Biol Blood Marrow Transplant 2014 Nov 10;20(11):1847-51. Epub 2014 Jul 10.

Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minnesota.

Mucolipidosis type II (MLII), or I-cell disease, is a rare but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. Although hematopoietic stem cell transplantation (HSCT) has been used to successfully treat some lysosomal storage diseases, only 2 cases have been reported on the use of HSCT to treat MLII. For the first time, we describe the combined international experience in the use of HSCT for MLII in 22 patients. Although 95% of the patients engrafted, overall survival was low, with only 6 patients (27%) alive at last follow-up. The most common cause of death post-transplant was cardiovascular complications, most likely due to disease progression. Survivors were globally delayed in development and often required complex medical support, such as gastrostomy tubes for nutrition and tracheostomy with mechanical ventilation. Although HSCT has demonstrated efficacy in treating some lysosomal storage disorders, the neurologic outcome and survival for patents with MLII were poor. Therefore, new medical and cellular therapies should be sought for these patients.
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http://dx.doi.org/10.1016/j.bbmt.2014.06.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4194244PMC
November 2014

Randomized trial of hydroxychloroquine for newly diagnosed chronic graft-versus-host disease in children: a Children's Oncology Group study.

Biol Blood Marrow Transplant 2012 Jan 30;18(1):84-91. Epub 2011 May 30.

Levine Children's Hospital, Charlotte, North Carolina 28232, USA.

The Children's Oncology Group conducted a multicenter Phase III trial for chronic graft-versus-host disease (cGVHD). The double-blind, placebo-controlled, randomized study evaluated hydroxychloroquine added to standard therapy for children with newly diagnosed cGVHD. The study also used a novel grading and response scoring system and evaluated clinical laboratory correlates of cGVHD. The primary endpoint was complete response (CR) after 9 months of therapy. Fifty-four patients (27 on each arm) were enrolled before closure because of slow accrual. The CR rate was 28% in the hydroxychloroquine arm versus 33% in the placebo arm (odds ratio [OR] = 0.77, 95% confidence interval [CI]: 0.20-2.93, P = .75) for 42 evaluable patients. For 41 patients with severity assessment at enrollment, 20 (49%) were severe and 18 (44%) moderate according to the National Institutes of Health Consensus Conference global scoring system. The CR rate was 15% for severe cGVHD and 44% for moderate cGVHD (OR = 0.24, 95% CI: 0.05-1.06, P = .07). Although the study could not resolve the primary question, it provided important information for future cGVHD study design in this population.
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http://dx.doi.org/10.1016/j.bbmt.2011.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627789PMC
January 2012

Low incidence of hepatic veno-occlusive disease in pediatric patients undergoing hematopoietic stem cell transplantation attributed to a combination of intravenous heparin, oral glutamine, and ursodiol at a single transplant institution.

Pediatr Transplant 2010 Aug 30;14(5):618-21. Epub 2009 Dec 30.

Division of Pediatric Hematology/Oncology and Stem Cell Transplantation, Schneider Children's Hospital, North Shore-Long Island Jewish Health System, New Hyde Park, NY 11040, USA.

We report the low incidence of hepatic VOD in pediatric patients with various diagnoses including hematologic malignancies and non-malignant conditions transplanted at our institution. Retrospective review of 188 patients who underwent HSCT and received a combined prophylactic regimen of intravenous heparin, oral glutamine, and ursodiol was undertaken. Analysis of the outcome of VOD revealed only one clinical case with acute myeloid leukemia; the patient developed hepatic VOD 10 days after receiving myeloablative chemotherapy with busulfan and CTX followed by HLA-matched related peripheral blood stem cell transplantation. The low incidence of hepatic VOD in an otherwise high-risk pediatric transplant population is an important observation, which may be partly attributed to this prophylactic regimen, and warrants further randomized clinical trials for confirmation.
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http://dx.doi.org/10.1111/j.1399-3046.2009.01285.xDOI Listing
August 2010

A pilot study of addition of amifostine to melphalan, carboplatin, etoposide, and cyclophosphamide with autologous hematopoietic stem cell transplantation in pediatric solid tumors-A pediatric blood and marrow transplant consortium study.

J Pediatr Hematol Oncol 2008 Mar;30(3):204-9

Department of Pediatrics, Section of Hematology/Oncology, New York Medical College, Valhalla, NY 10595, USA.

Limited information is available regarding the use of amifostine in pediatric hematopoietic stem cell transplant (HSCT) patients. Melphalan, carboplatin, etoposide +/- cyclophosphamide is a commonly used preparatory regimen in pediatric solid tumor HSCT. Therefore, we decided to determine the feasibility of the addition of amifostine (750 mg/m b.i.d. x 4 d) to melphalan (200 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) (level 1) and escalating doses of cyclophosphamide (3000 mg/m and 3800 mg/m, levels 2 and 3, respectively) followed by autologous HSCT. Thirty-two patients with a variety of pediatric solid tumors were studied. Seventeen patients were accrued at level 1, 9 at level 2, and 6 at level 3. Major toxicities during the administration of the preparatory regimen were hypocalcemia, emesis, and hypotension. Hypocalcemia required aggressive calcium supplementation during the conditioning phase. No dose limiting toxicities were encountered at level 3. Amifostine at 750 mg/m b.i.d. for 4 days can be administered with a double alkylator regimen consisting of melphalan (200 mg/m), cyclophosphamide (up to 3800 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) with manageable toxicities.
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http://dx.doi.org/10.1097/MPH.0b013e318162bd0cDOI Listing
March 2008

Use of gemtuzumab ozogamicin in the treatment of pediatric relapsed/ refractory Acute Myeloid Leukemia.

Turk J Haematol 2008 Mar;25(1):36-41

Gemtuzumab ozogamicin (GO, MylotargTM) is an antibody-targeted chemotherapy agent that has been studied in acute myeloid leukemia (AML) at first relapse in adults. There is limited experience in pediatric patients. We report six patients with refractory/relapsed CD33+AML who were treated with GO on compassionate-use basis. One patient attained remission. One patient is still alive following hematopoietic stem cell transplantation (HSCT), and one patient died in remission. Two patients were refractory and three patients had a response with <5% blasts in the bone marrow. Fever and chills, hypotension and hypoxia were observed as side effects. Three patients developed veno-occlusive disease (VOD) of the liver. Two of these three patients had persistence of VOD at the time of their deaths. One patient treated postSCT had bone marrow response without VOD. GO should be used cautiously in chemotherapy-refractory AML pediatric patients due to the high incidence of VOD.
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March 2008

Capsule endoscopy as a diagnostic tool in the evaluation of graft-vs.-host disease.

Pediatr Transplant 2006 Mar;10(2):252-4

Division of Pediatric Gastroenterology and Nutrition, North Shore--LIJ Health System Schneider Children's Hospital, New Hyde Park, NY 11040, USA.

Capsule endoscopy is a relatively new technology that has allowed gastroenterologists to visualize the mucosa of the small intestine. This technology is playing an expanding role in both adult and pediatric gastroenterology. In this report, we present an 8-yr-old child following allogeneic hematopoietic cell transplantation who developed large volume bloody diarrhea requiring multiple packed red blood cell transfusions that was resistant to aggressive therapy for GVHD. The capsule endoscopy performed on this patient provided significant information not provided by upper endoscopy and colonoscopy that allowed for successful treatment changes. This case demonstrates that capsule endoscopy is a diagnostic tool that may play an important role in the assessment of patients, including children, with possible GVHD.
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http://dx.doi.org/10.1111/j.1399-3046.2005.00454.xDOI Listing
March 2006

Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases.

Biol Blood Marrow Transplant 2006 Feb;12(2):184-94

Duke University Medical Center, Durham, North Carolina 27710, USA.

The Cord Blood Transplantation Study (COBLT), sponsored by the National Heart, Lung, and Blood Institute, is a phase II multicenter study designed to evaluate the use of cord blood in allogeneic transplantation. In this report, we evaluated the outcomes of cord blood transplantation in 69 patients with lysosomal and peroxisomal storage diseases. Patients with mucopolysaccharidoses I to III, mucolipidoses (ML) II (n = 36), adrenoleukodystrophy (n = 8), metachromatic leukodystrophy (n = 6), Krabbe disease (n = 16), and Tay-Sachs disease (n = 3) were enrolled between August 1999 and June 2004. All patients received the same preparative regimen, graft-versus-host disease (GVHD) prophylaxis, and supportive care. End points included survival, engraftment, GVHD, and toxicity. Sixty-nine patients (64% men; 81% white) with a median age of 1.8 years underwent transplantation with a median cell dose of 8.7 x 10(7)/kg. One-year survival was 72% (95% confidence interval, 61%-83%). The cumulative incidence of neutrophil engraftment by day 42 was 78% (95% confidence interval, 67%-87%) at a median of 25 days. Grade II to IV acute GVHD occurred in 36% of patients. Cord blood donors are readily available for rapid transplantation. Cord blood transplantation should be considered as frontline therapy for young patients with lysosomal and peroxisomal storage diseases.
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http://dx.doi.org/10.1016/j.bbmt.2005.09.016DOI Listing
February 2006

Concordant rhabdoid tumor of the kidney in a set of identical twins with discordant outcomes.

J Pediatr Hematol Oncol 2003 Jun;25(6):491-4

Division of Pediatric Hematology/Oncology and Stem Cell Transplantation, Schneider Children's Hospital, Manhasset, New York 11040, USA.

We report identical twin boys who each had stage IV rhabdoid tumor of the left kidney at the age of 5 months and 2 years, respectively. The 5-month-old boy, despite receiving chemotherapy, died of progressive disease at the age of 12 months. Following resection of the tumor, his twin brother was treated with 6 cycles of combination chemotherapy consisting of cisplatinum, doxorubicin, vincristine, cyclophosphamide, and actinomycin-D alternating with ifosfamide and etoposide. After complete regression of lung and brain metastases, he received high-dose thiotepa, etoposide, and cyclophosphamide, followed by autologous peripheral stem cell rescue. The patient is presently alive and free of disease 6 years posttransplant. High-dose chemotherapy followed by autologous stem cell transplant may be an effective front-line therapeutic approach for patients with metastatic rhabdoid tumor of the kidney.
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http://dx.doi.org/10.1097/00043426-200306000-00013DOI Listing
June 2003