Optimal Donor for African Americans with Hematologic Malignancy: HLA-Haploidentical Relative or Umbilical Cord Blood Transplant.

Although hematopoietic cell transplantation from an HLA-matched unrelated donor is potentially curative for hematologic malignancies, survival is lower for African Americans compared with Caucasians. Because only approximately 20% of African Americans will have an HLA-matched unrelated donor, many of these patients undergo HLA-haploidentical relative or umbilical cord blood transplantation. In this study, we analyzed outcomes after HLA-haploidentical related donor (n = 249) and umbilical cord blood (n = 118) transplantations in African American patients with hematologic malignancy between 2008 and 2016. The predominant disease was acute myelogenous leukemia for recipients of both types of donor grafts. The incidences of grade II-IV and III-IV acute graft-versus-host disease were higher after umbilical cord blood transplantation compared with HLA-haploidentical relative transplantation (56% and 29%, respectively, versus 33% and 11%, respectively; P < .0001). The 2-year incidence of transplantation-related mortality adjusted for age and conditioning regimen intensity was higher after umbilical cord blood transplantation compared with HLA-haploidentical related donor transplantation (31% versus 18%; P = .008); however, there were no between-group differences in the 2-year adjusted incidence of relapse (30% versus 34%; P = .51), overall survival (54% versus 57%; P = .66), or disease-free survival (43% versus 47%; P = .46). Our findings show that the use of HLA-haploidentical and umbilical cord blood transplants expands the access to transplantation with comparable leukemia-free and overall survival for African Americans with hematologic malignancies.

Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States.

In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥70 years with hematologic malignancies across the United States. Adults ≥70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥70 years underwent HCT across 103 transplant centers. The number and proportion of allografts performed in this population rose markedly over the past decade, accounting for 0.1% of transplants in 2000 to 3.85% (N = 298) in 2013. Acute myeloid leukemia and myelodysplastic syndromes represented the most common disease indications. Two-year OS and PFS significantly improved over time (OS: 26% [95% confidence interval (CI), 21% to 33%] in 2000-2007 to 39% [95% CI, 35% to 42%] in 2008-2013, P < .001; PFS: 22% [16% to 28%] in 2000-2007 to 32% [95% CI, 29% to 36%] in 2008-2013, P = .003). Two-year TRM ranged from 33% to 35% and was unchanged over time (P = .54). Multivariable analysis of OS in the modern era of 2008-2013 revealed higher comorbidity by HCT comorbidity index ≥3 (hazard ratio [HR], 1.27; P = .006), umbilical cord blood graft (HR, 1.97; P = .0002), and myeloablative conditioning (HR, 1.61; P = .0002) as adverse factors. Over the past decade, utilization and survival after allogeneic transplant have increased in patients ≥70 years. Select adults ≥70 years with hematologic malignancies should be considered for transplant.

One-unit versus two-unit cord-blood transplantation for hematologic cancers.

BACKGROUND: Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation. METHODS: Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival. RESULTS: Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor-recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P=0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II-IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit. CONCLUSIONS: We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. (Funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; ClinicalTrials.gov number, NCT00412360.).

Double umbilical cord blood transplantation after novel myeloablative conditioning using a regimen of fludarabine, busulfan, and total lymphoid irradiation.

We conducted a pilot study evaluating double umbilical cord blood transplantation (dCBT) after myeloablative conditioning with fludarabine and busulfan 3.2 mg/kg i.v. × 4, followed by total lymphoid irradiation at 400 cGy (FluBu4/TLI) for any indicated hematological disorder for patients without a suitable donor. Twenty patients with predominantly high-risk disease underwent dCBT according to protocol. The regimen was well tolerated, with mucositis as the primary observed toxicity (n = 19). The cumulative incidence of neutrophil engraftment was 89% (95% confidence interval [CI], 64% to 97%), with a median time to recovery of 16 days (range, 12 to 31 days). All evaluable patients with neutrophil engraftment achieved complete donor chimerism by day 40. The cumulative incidence of grades III and IV acute graft-versus-host disease (GVHD) at day 100 was 10% (95% CI, 2% to 27%), and the cumulative incidence of chronic GVHD was 35% (95% CI, 16% to 55%) by the end of the study. At 1 year, the cumulative incidence of treatment-related mortality (TRM) was 35% (95% CI, 16% to 55%). The leading cause of nonrelapse mortality was acute GVHD (n = 4), followed by graft failure (n = 2) and chronic GVHD (n = 1). TRM was significantly associated with a pretransplantation hematopoietic cell transplantation-specific comorbidity index score ≥ 3 (P = .005). At 1 year, disease relapse occurred in 6 patients and overall survival was 40% (95% CI, 19% to 60%). We conclude that FluBu4/TLI is an adequate preparative regiment before dCBT, providing high engraftment rates and relatively early neutrophil recovery. The best survival outcomes were seen in patients without significant comorbidities before transplantation, and outcomes are comparable to previously published dCBT studies.

Ciprofloxacin versus levofloxacin prophylaxis in hematopoietic stem cell transplantation: A randomized trial.

OBJECTIVES: We aimed to assess whether there is a difference between ciprofloxacin and levofloxacin as prophylaxis in hematopoietic stem cell transplant (SCT) recipients. METHODS: This is a prospective, randomized trial in patients receiving SCT at Henry Ford Health in the United States of America. We randomly assigned patients (1:1) to receive ciprofloxacin or levofloxacin. The primary outcome was incidence of bloodstream bacterial infections (BSI) up to day 60 after SCT. RESULTS: Between June 4, 2018, and May 23, 2022, we randomly assigned 308 consecutive patients to receive ciprofloxacin (154 patients) or levofloxacin (154 patients). BSI was similar in both the ciprofloxacin and levofloxacin groups (18 [11.7%] vs 18 [11.7%]). Pneumonia was more frequent in the ciprofloxacin group compared to the levofloxacin group (18 [18%] vs 7 [23%]; relative risk 2.57, 95% CI 1.11-5.98; p = 0.028). There were no differences in neutrophil engraftment, fever, Clostridium difficile infection, relapse incidence, overall survival, nonrelapse mortality, length of stay post-SCT, or intensive care unit admission. CONCLUSION: Although both prophylaxis regimens demonstrated the same efficacy in SCT recipients, levofloxacin prophylaxis led to less pneumonia in the first 60 days post-SCT. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, NCT03850379.

Acquired genomic copy number aberrations and survival in chronic lymphocytic leukemia.

Genomic aberrations are of predominant importance to the biology and clinical outcome of patients with chronic lymphocytic leukemia (CLL), and FISH-based genomic risk classifications are routinely used in clinical decision making in CLL. One of the known limitations of CLL FISH is the inability to comprehensively interrogate the CLL genome for genomic changes. In an effort at overcoming the existing limitations in CLL genome analysis, we have analyzed high-purity DNA isolated from FACS-sorted CD19(+) cells and paired CD3(+) or buccal cells from 255 patients with CLL for acquired genomic copy number aberrations (aCNAs) with the use of ultra-high-density Affymetrix SNP 6.0 arrays. Overall, ≥ 2 subchromosomal aCNAs were found in 39% (100 of 255) of all cases analyzed, whereas ≥ 3 subchromosomal aCNAs were detected in 20% (50 of 255) of cases. Subsequently, we have correlated genomic lesion loads (genomic complexity) with the clinical outcome measures time to first therapy and overall survival. With the use of multivariate analyses incorporating the most important prognostic factors in CLL together with SNP 6.0 array-based genomic lesion loads at various thresholds, we identify elevated CLL genomic complexity as an independent and powerful marker for the identification of patients with aggressive CLL and short survival.

Clofarabine and busulfan conditioning facilitates engraftment and provides significant antitumor activity in nonremission hematologic malignancies.

Patients with hematologic malignancies not in remission before allogeneic hematopoietic stem cell transplantation (HSCT) have a poor prognosis. To improve the antitumor activity of conditioning, we combined clofarabine with myeloablative doses of busulfan in a phase 1/2 study in nonremission hematologic malignancies. Forty-six patients were enrolled, including 31 patients with nonremission acute myelogenous leukemia (AML). Patients had a median age of 53 years, with a median comorbidity index of 3. Donors were unrelated, HLA mismatched, or both in 59% of patients. Common grade III to IV nonhematologic toxicities included transient transaminitis (50%), mucositis (24%), hand-foot syndrome (13%), transient hypoxia (13%), nausea/vomiting (9%), and diarrhea (9%). All patients engrafted. Complete remission was achieved in 80% of all patients by day +30 and in 100% of AML patients without prior hematopoietic stem cell transplantation. Two-year nonrelapse mortality for all patients was 31%, and overall survival was 28%. In AML, the overall survival was 48% at 1 year and 35% at 2 years. These data suggest that clofarabine combined with myeloablative doses of busulfan is well tolerated, secures engraftment, and possesses significant antitumor activity, particularly in nonremission AML. This study is registered at www.ClinicalTrials.gov under identifier NCT00556452.

TNF-inhibition with etanercept for graft-versus-host disease prevention in high-risk HCT: lower TNFR1 levels correlate with better outcomes.

Graft-versus-host disease (GVHD) causes most non-relapse mortality (NRM) after alternative donor (unrelated and mismatched related) hematopoietic cell transplant (HCT). We previously showed that increases in day +7 TNF-receptor-1 (TNFR1) ratios (posttransplantation day +7/pretransplantation baseline) after myeloablative HCT correlate with outcomes including GVHD, NRM, and survival. Therefore, we conducted a phase II trial at 2 centers, testing whether the addition of the TNF-inhibitor etanercept (25 mg twice weekly from start of conditioning to day +56) to standard GVHD prophylaxis would lower TNFR1 levels, reduce GVHD rates, and improve NRM and survival. Patients underwent myeloablative HCT from a matched unrelated donor (URD; N = 71), 1-antigen mismatched URD (N = 26), or 1-antigen mismatched related donor (N = 3) using either total body irradiation (TBI)-based conditioning (N = 29) or non-TBI-based conditioning (N = 71). Compared to historical controls, the increase in posttransplantation day +7 TNFR1 ratios was not altered in patients who received TBI-based conditioning, but was 40% lower in patients receiving non-TBI-based conditioning. The latter group experienced relatively low rates of severe grade 3 to 4 GVHD (14%), 1-year NRM (16%), and high 1-year survival (69%). These findings suggest that (1) the effectiveness of TNF-inhibition with etanercept may depend on the conditioning regimen, and (2) attenuating the expected rise in TNFR1 levels early posttransplantation correlates with good outcomes.

Early intervention with antithrombin III therapy to prevent progression of hepatic venoocclusive disease.

Venoocclusive disease (VOD) is the most frequent cause of early nonrelapse mortality among patients receiving high-dose chemoradiotherapy and hematopoietic stem cell transplantation. Endothelial injury of sinusoids and hepatic veins following chemotherapy is considered the initial event in the development of VOD. Activation of the coagulation cascade and inflammatory processes following endothelial injury results in a hypercoagulable state and a localized consumption of the natural anticoagulants, antithrombin III, protein C and protein S. The resultant coagulopathy can lead to multiorgan dysfunction and death. The objective was to retrospectively study the largest series of patients that has received antithrombin III for the treatment of VOD following hematopoietic stem cell transplantation. A total of 48 patients were diagnosed with VOD post hematopoietic stem cell transplantation (median age, 39 years; range, 1-69 years); 38 of the 48 received a nonradiation-based conditioning regimen and 21 of 48 received a transplant from an unrelated donor. Treatment was primarily directed at early intervention rather than prophylactic therapy to correct the antithrombin III deficiency associated with VOD. We attempted to achieve antithrombin III levels greater than 120%. There was no significant treatment-related morbidity. The overall 100-day mortality for the treatment cohort was 17%, with 10% for the mild/moderate group and 39% for the severe group, respectively. In conclusion, the encouraging results of this study suggest that this antithrombin III treatment should be further considered in patients with severe VOD.

Chimerism in Myeloid Malignancies following Stem Cell Transplantation Using FluBu4 with and without Busulfan Pharmacokinetics versus BuCy.

In the era of precision medicine, the impact of personalized dosing of busulfan is not clear. We undertook a retrospective analysis of 78 patients with myeloid malignancies who received fludarabine and busulfan (FluBu4) with or without measuring Bu pharmacokinetics (Bu PK) and those who received busulfan with cyclophosphamide (BuCy). Fifty-five patients received FluBu4, of whom 21 had Bu PK measured, and 23 patients received BuCy. Total donor cell chimerism showed that the percentage of patients maintaining 100% donor chimerism on day 100 was 66.7%, 38.2%, and 73.9% in the FluBu4 with PK, FluBu4 with no PK, and BuCy, respectively (P = .001). Patients who had decreasing donor chimerism by day 100 were 23.8%, 52.9%, and 26.1% in the FluBu4 with PK, FluBu4 with no PK, and BuCy, respectively (P = .04). Bu PK group had fewer patients with less than 95% donor chimerism on day 30, which was not statistically significant, 5% (FluBu4 PK), 31% (FluBu4 with no PK), and 21% (BuCy) (P = .18). Survival distributions were not statistically significant (P = .11). Thus, personalized drug dosing can impact donor chimerism in myeloid malignancies. This will need to be examined in larger retrospective multicenter studies and prospective clinical trials.

Sirolimus-itraconazole interaction in a hematopoietic stem cell transplant recipient.

Interactions between azole antifungal agents and immunosuppressants that are metabolized by cytochrome P450 3A4 (chiefly calcineurin inhibitors) are well documented. Interactions between itraconazole and sirolimus are known to occur in patients after solid organ transplantation, but interactions in hematopoietic stem cell transplant (HSCT) recipients have yet to be reported in the literature. We describe an allogeneic HSCT recipient who experienced supratherapeutic trough levels of sirolimus as a result of its coadministration with itraconazole. This patient was a 20-year-old African-American man who underwent HSCT for treatment of myelodysplastic syndrome with severe aplastic anemia. After several regimen changes, the patient received oral itraconazole 200 mg every 12 hours and sirolimus at a dosage of 7 mg/day on days 76-80 and 5 mg/day on days 81 and 82. His sirolimus whole blood trough levels were 17.5 and 35.6 ng/ml on days 80 and 82, respectively (therapeutic range 5-15 ng/ml). An interaction between itraconazole and sirolimus was suspected, and sirolimus was withheld on days 83-90. On day 90, the patient's sirolimus trough level had normalized to 4.4 ng/ml. Sirolimus was resumed at 1-2 mg/day, with adjustments as needed to maintain trough levels of 10-15 ng/ml. Both the itraconazole and sirolimus were eventually were discontinued. The patient died, however, from a disseminated adenovirus infection leading to end-organ failure. Sirolimus is extremely sensitive to the inhibitory potential of azole antifungals. We propose that itraconazole also has a potent effect on sirolimus metabolism. Preemptive sirolimus dosage reduction and close monitoring of its whole blood trough levels are required whenever this combination is considered to avoid immunosuppressant toxicity in already critically ill patients.

Choice of Unmanipulated T Cell Replete Graft for Haploidentical Stem Cell Transplant and Posttransplant Cyclophosphamide in Hematologic Malignancies in Adults: Peripheral Blood or Bone Marrow-Review of Published Literature.

Allogeneic hematopoietic stem cell transplantation (SCT) is often the only curative option for many patients with malignant and benign hematological stem cell disorders. However, some issues are still of concern regarding finding a donor like shrinking family sizes in many societies, underrepresentation of the ethnic minorities in the registries, genetic variability for some races, and significant delays in obtaining stem cells after starting the search. So there is a considerable need to develop alternate donor stem cell sources. The rapid and near universal availability of the haploidentical donor is an advantage of the haploidentical SCT and an opportunity that is being explored currently in many centers especially using T cell replete graft and posttransplant cyclophosphamide. This is probably because it does not require expertise in graft manipulation and because of the lower costs. However, there are still lots of unanswered questions, like the effect of use of bone marrow versus peripheral blood as the source of stem cells on graft-versus-host disease, graft versus tumor, overall survival, immune reconstitution, and quality of life. Here we review the available publications on bone marrow and peripheral blood experience in the haploidentical SCT setting.

Chromosome analyses of 16 cases of Wilms tumor: different pattern in unfavorable histology.

Cytogenetic analyses of 16 cases of Wilms tumor with abnormal karyotypes were reviewed, 15 cases of unilateral tumor and 1 bilateral. Three tumors exhibited an unfavorable histology (i.e., anaplastic changes); the rest fell into the favorable histology group. Of the 17 tumors with abnormal clonal aberrations, 9 tumors were hyperdiploid (53%), 7 had pseudodiploid karyotypes (41%), and 1 was hypodiploid (6%). The most common numerical aberrations in descending order of frequency were gain of chromosomes 12, 8, and 6 and loss of chromosome 16. Structural rearrangements mostly involved chromosome 1, followed by chromosomes 7, 14, and 17. Clustering of breaks around 1p22 approximately p31-->pter resulting in partial loss of 1p was the most frequent structural aberration. Additionally, i(7q) was observed as a sole abnormality in two tumors and a 7p translocation in two other tumors. Two other recurrent abnormalities were a partial deletion of 14q, seen in three tumors, and complete loss of chromosome 14 in one tumor. All three Wilms tumors with unfavorable histology had abnormalities of 17p, resulting in TP53 gene deletion. These findings provide further support for the importance of gains of chromosomes 12, 8, and 6 and loss of 1p in the development of Wilms tumor. The results also support the association of unfavorable-histology Wilms tumors with TP53 deletion. The nonrandom losses of 16/16q, 7p, and 14q may point to the importance of genomic imbalance in the pathogenetic consequences and progression of Wilms tumor.

Elafin is a biomarker of graft-versus-host disease of the skin.

Graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation, affects the skin, liver, and gastrointestinal tract. There are no plasma biomarkers specific for any acute GVHD target organ. We used a large-scale quantitative proteomic discovery procedure to identify biomarker candidates of skin GVHD and validated the lead candidate, elafin, with enzyme-linked immunosorbent assay in samples from 492 patients. Elafin was overexpressed in GVHD skin biopsies. Plasma concentrations of elafin were significantly higher at the onset of skin GVHD, correlated with the eventual maximum grade of GVHD, and were associated with a greater risk of death relative to other known risk factors (hazard ratio, 1.78). We conclude that elafin has significant diagnostic and prognostic value as a biomarker of skin GVHD.

Reduced intensity transplantation for metastatic renal cell cancer with 2-year follow-up.

Metastatic renal cell carcinoma (RCC) is a disease that is resistant to conventional systemic therapy. Nonmyeloablative allogeneic stem cell transplant has activity in patients with metastatic RCC. This approach has been used in related donor transplantation but there are limited data on outcomes in the setting of unrelated donor (URD) transplantation. This phase II trial assessed the efficacy, safety, and responses in 16 patients, 10 related and 6 URD transplants after a reduced intensity conditioning regimen and stem cell transplant as a treatment for metastatic RCC. Sixteen patients received a conditioning consisting of either fludarabine, cyclophosphamide (n=11) or fludarabine, total body irradiation (n=5) followed by transplantation from an HLA-matched sibling donor or a unrelated HLA-donor. Cyclosporine and mycophenolate mofetil were administered as posttransplant immunosuppression. Patients were monitored for engraftment by short tandem repeat for myeloid and lymphoid lineages and clinical response was assessed by serial imaging. All patients achieved donor chimerism, 7 patients developed acute, grades 2 to 3, graft-versus-host disease. Chronic graft-versus-host disease occurred in 6 patients and transplant-related mortality was 12%. Of the 10 related donors, 1 obtained a complete response, 3 had a partial response, and 3 had stable disease. In the 6 patients who underwent URD transplant, 1 obtained a complete response and 1 patient had stable disease. These results suggest that similar outcomes are possible where either related or URD were used as the stem cell source in reduced intensity stem cell transplant for metastatic RCC.

Thalidomide for the treatment of histiocytic sarcoma after hematopoietic stem cell transplant.

Histiocytic sarcoma (HS) is a rare neoplasm of uncertain etiology. Most recently, the diagnostic criteria for this entity have been revised with inclusion of diagnostic modalities such as immunohistochemical and cytogentic techniques. HS tends to have an aggressive clinical course and presents with systemic symptoms of fever, weight loss, adenopathy, hepatosplenomegly, rash, and pancytopenia. Thalidomide is a promising agent that may exert a therapeutic benefit in HS. We report a case of a 48-year-old female with HS who presented with fever, weight loss, fatigue, generalized anasarca, and pancytopenia. She underwent multi-agent chemotherapy followed by matched unrelated hematopoietic stem cell transplant. Her disease recurred and thalidomide therapy was started, with her overall disease burden significantly reduced as measured radiographically.

The sulfone syndrome secondary to dapsone prophylaxis in a patient undergoing unrelated hematopoietic stem cell transplantation.

Dapsone is commonly used for pneumocystis carinii pneumonia (PCP) prophylaxis in immunocompromised patients. It has been used as an alternative therapy in the hematopoietic stem cell transplant (HSCT) setting in patients who can't tolerate trimethoprim-sulfamethoxazole. The Sulfone syndrome is not a well-known sequela of dapsone therapy and occurs at various doses, ranging from 50-300 mg/d. In all cases the syndrome occurs within 2 months of initiating therapy. Its clinical manifestations include: fever, methemoglobinemia, hemolytic anemia, exfoliative dermatitis and transaminits. A 51-year old female underwent a matched unrelated hematopoiectic stem cell transplant for acute mylogenous leukemia. Dapsone therapy was initiated on day +28 at a dose of 100 mg/day for PCP prophylaxis secondary to the patient's history of a sulfonamide allergy. On day +59, one month after initiation of therapy she developed hepatitis, hemolytic anemia, fever and methemoglobinemia of 8%. She was transferred to the intensive care unit and subsequently developed an exfoliative dermatitis. We conclude that the clinical presentation of this patient after HSCT on dapsone therapy coincide with the sulfone syndrome not previously described in a patients after HSCT.

Palifermin in a hematopoietic stem cell transplant patient with osteonecrosis of the jaw.

This case report describes the use of palifermin in a multiple myeloma patient with a history of osteonecrosis of the jaw (ONJ) for the prevention of high-dose chemotherapy-induced mucositis. Following the day of autologous stem cell infusion, palifermin was discontinued secondary to adverse events. Specifically, palifermin-associated macroglossia seemed to exacerbate the pain localized in the oral cavity area affected by ONJ, necessitating escalated doses of narcotic analgesics. When contemplating palifermin as a mucosal protectant in a hematopoietic stem cell transplant patient with ONJ, a careful benefit-to-risk assessment is in order to ensure optimal effectiveness without undue harm.

Primitive neuroectodermal tumor (PNET) of the uterus in a renal allograft patient: a case report.

The incidence of malignancy after renal transplant has been reported to range from 4% to 18%. Tumors of the skin and lip tend to be the most common with non-Hodgkin lymphoma comprising 20% of all neoplasms. Primitive neuroectodermal tumors (PNET) are collectively described as being a part of the Ewing sarcoma family of tumors. PNET occur more commonly in the second decade of life, predominantly affecting Whites and Hispanics, and rarely occur in individuals of African or Asian descent. The most common primary site of involvement is along the central axis, particularly the chest (Askin tumor), but it can arise in any soft tissue. PNET also occur in the head and neck. PNET involving the cervix, urinary bladder, uterus, and vagina have been reported. We describe a case of a 15-year-old female who, 9 years after receiving a living related renal transplant, developed a post-transplant PNET of the uterus.

Anti-thrombin III in the management of hematopoietic stem-cell transplantation-associated toxicity.

OBJECTIVE: To describe the evidence assessing the use of anti-thrombin III (AT-III) in the management of toxicity associated with hematopoietic stem-cell transplantation (HSCT)-conditioning regimens. DATA SOURCES: Clinical literature was accessed through conference proceedings, EMBASE, the Cochrane database, and MEDLINE (1966-December 2003). STUDY SELECTION AND DATA EXTRACTION: Case reports, small case series, case-control and cohort studies, and randomized controlled trials of AT-III in HSCT were evaluated. Publications examining AT-III use in the non-HSCT setting were also explored. Key search terms included AT-III, transplantation, and veno-occlusive disease (VOD). DATA SYNTHESIS: Severe VOD and ensuing multiple organ dysfunction is associated with high mortality in HSCT. A low AT-III level has been shown to correlate with the development of organ dysfunction. Phase II trials, case series, and one small, randomized, placebo-controlled study suggest a benefit when AT-III therapy is instituted early in the course of VOD/multiple organ dysfunction syndrome. In all of these reports, AT-III use was devoid of adverse events. CONCLUSIONS: Although further studies are needed to ascertain the optimal target level, method, and duration of administration, AT-III is still a viable alternative for the treatment of severe VOD and ensuing multiple organ dysfunction.