Karina Danner-Koptik

Second malignancies after autologous hematopoietic cell transplantation in children.

Childhood autologous hematopoietic cell transplant (auto-HCT) survivors can be at risk for secondary malignant neoplasms (SMNs). We assembled a cohort of 1487 pediatric auto-HCT recipients to investigate the incidence and risk factors for SMNs. Primary diagnoses included neuroblastoma (39%), lymphoma (26%), sarcoma (18%), central nervous system tumors (14%) and Wilms tumor (2%). Median follow-up was 8 years (range, <1–21 years). SMNs were reported in 35 patients (AML/myelodysplastic syndrome (MDS)=13, solid cancers=20, subtype missing=2). The overall cumulative incidence of SMNs at 10 years from auto-HCT was 2.60% (AML/MDS=1.06%, solid tumors=1.30%). We found no association between SMNs risk and age, gender, diagnosis, disease status, time since diagnosis or use of TBI or etoposide as part of conditioning. OS at 5-years from diagnosis of SMNs was 33% (95% confidence interval (CI), 16–52%). When compared with age- and gender-matched general population, auto-HCT recipients had 24 times higher risks of developing SMNs (95% CI, 16.0–33.0). Notable SMN sites included bone (N=5 SMNs, observed (O)/expected (E)=81), thyroid (N=5, O/E=53), breast (N=2, O/E=93), soft tissue (N=2, O/E=34), AML (N=6, O/E=266) and MDS (N=7, O/E=6603). Risks of SMNs increased with longer follow-up from auto-HCT. Pediatric auto-HCT recipients are at considerably increased risk for SMNs and need life-long surveillance for SMNs.

Secondary malignant neoplasms after high-dose chemotherapy and autologous stem cell rescue for high-risk neuroblastoma

Outcomes for high‐risk neuroblastoma remain poor. Modern treatment protocols utilizing intense induction followed by myeloablative consolidation chemotherapy with autologous stem cell rescue (ASCR) have improved survival rates, but the long‐term sequelae, including development of secondary malignant neoplasms (SMN), are just now surfacing.

Models of Cancer Survivorship Care for Adolescents and Young Adults

OBJECTIVES To review the literature on adolescent and young adult (AYA) oncology, discuss survivorship models of care, and focus on the unique needs of AYA patients with transition of care from treatment to survivorship. DATA SOURCES Peer-reviewed literature, workshop summaries, clinical practice guidelines. CONCLUSION Advancements have been made for AYAs with regard to identifying risk factors from cancer treatment and the need for ongoing follow-up care. Survivors face several unique care transitions. Several models of survivorship care are available for AYAs. IMPLICATIONS FOR NURSING PRACTICE The responsibilities of survivorship care for AYA patients fall on clinical providers, researchers, the government, advocacy groups as well as the survivors and families themselves. Nurses must remain cognizant and educated on AYA survivorship issues.

Haploidentical related umbilical cord blood stem cell transplant in a child with acute non-lymphocytic leukemia

Umbilical cord blood stem cells (UCBSC) were used to reconstitute hematopoiesis following myeloablative therapy in a 13-month-old infant with acute nonlymphocytic leukemia (ANLL):FAB-M5 who had failed to sustain a chemotherapeutic remission. The patient’s mother was 18 weeks pregnant with her second child at the time of diagnosis. Amniocentesis revealed that the fetus was HLA-haploidentical with the patient at the paternally inherited allele. The umbilical cord blood was harvested and processed by Ficoll centrifugation with 100% recovery of 5 × 107 mononuclear cells/kg and then cryopreserved. Two weeks after collection the cells were thawed and then infused into the patient following conditioning with total body irradiation, cyclophosphamide, and etoposide. Graft-versus-host-disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. The patient experienced clinical grade I GVHD consisting of skin involvement only that resolved within 2 weeks following the addition of corticosteroids. Engraftment was achieved with an absolute neutrophil count (ANC) above 0.5 × 109/l on day 16, a platelet count above 50 × 109/1 on day 56, platelet transfusion independence on day 32 and red blood cell transfusion independence after day 44. Three months following transplantation restriction fragment length polymorphisms (RFLP) revealed no discernible difference between the donor and the recipient. The patient remains in remission without evidence of GVHD 23 months post-transplant.

Red cell salvage and reinfusion in pediatric bone marrow donors.

We evaluated the use of a semi-automated processing technique to salvage red blood cells from pediatric bone marrow donors to minimize the risk of severe anemia following bone marrow harvest and ABO incompatibility in the recipient. Sixty healthy, HLA-matched, pediatric donors of bone marrow hematopoietic cells with a median age 8.0 years (2–19) were studied. Thirteen of the donor–recipient pairs were ABO incompatible. There were 60 recipients with a median age of 8.6 years (2 months to 20.8 years). Bone marrow was harvested under general anesthesia, filtered in the operating room and then transferred to the stem cell laboratory for processing. Samples were obtained for cell count, CD34+ quantification, colony assay, viability, and bacteriologic cultures before and after processing. The cells were processed in a semi-automated closed system (Stericel, Terumo) by density gradient separation with Ficoll–Hypaque and then washed. Two aliquots were obtained: one containing the mononuclear cell layer to be infused to the recipient and the other the washed red cells to be infused to the donor. The median volume harvested was 608 ± 40.42 ml (278–1409), while the final volume infused was 174 ± 10.75 ml (30.2–380) P < 0.0001, representing a decrease of 72% of the volume infused. the nucleated cell count harvested was 1.6 × 1010 ± 0.1 (0.56–3.2), while the count infused was 6.9 × 109 ± 0.1 (0.12–5.4) P < 0.0001. the median mononuclear cell count (mnc) per kg harvested was 0.67 × 108 ± 0.05 (0.18–2.0) vs an infused cell number of 1.3 × 108 MNC/kg ± 0.1 (0.6–33.6) P < 0.0001. the cd34+ cells harvested were 2.8 × 106/kg ± 0.1 (0.25–10.2) vs an infused number of 6.0 × 106/kg ± 0.5 (0.84–31.0) P < 0.0001. the viability before and after processing was 99%. red cell salvage performed in a semi-automated closed system is safe and reduces the risk of post-bone marrow harvest anemia in pediatric donors, decreases the volume infused into the donor and enriches the mononuclear and cd34+ cell population, without affecting hematopoietic reconstitution.

Exostoses as a Long-Term Sequela After Pediatric Hematopoietic Progenitor Cell Transplantation: Potential Causes and Increase Risk of Secondary Malignancies from Ann & Robert H. Lurie Children's Hospital of Chicago

Allogeneic hematopoietic progenitor cell transplantation (HPCT) is a curative therapy for pediatric patients with both malignant and nonmalignant diseases. Single or multiple benign exostoses or osteochondromas have been reported after total body irradiation (TBI), as well as after focal irradiation. Patients exposed to TBI at a young age are at highest risk of developing exostoses. The objective of this institutional review board-approved study was to look at potential factors, besides radiation, that may play a role in development of exostoses. All patients who underwent allogeneic and autologous HPCT at a single institution between March 1992 and December 2003 and who developed an exostosis identified by clinical findings or as an incidental finding on a radiologic study were included. A case-control design matched patients with controls who had the same stem cell source.

Late Effects in Pediatric High-risk Neuroblastoma Survivors after Intensive Induction Chemotherapy Followed by Myeloablative Consolidation Chemotherapy and Triple Autologous Stem Cell Transplants

Multimodal treatment in high-risk neuroblastoma has modestly improved survival; limited data exist on the late effects from these regimens. We report the sequelae of treatment incorporating 3 consecutive cycles of high-dose therapy and autologous stem cell transplants (ASCTs) without the use of total body irradiation (TBI). We reviewed the medical records of 61 patients treated on or following the Chicago Pilot 2 protocol between 1991 and 2008. Of the 25 patients who are alive (41%), 19 had near complete data to report. Specific treatment modalities and therapy-related side effects were collected. Fourteen of these 19 patients (74%) received 3 cycles of high-dose therapy with ASCT; follow-up occurred over a median of 13.9 years (range, 5.8 to 18.8 y). The majority of late effects were endocrine-related, including growth failure, hypothyroidism, and hypogonadism. Patients also developed secondary neoplasms and skeletal deformities. The most frequent sequela was hearing loss, seen in 17/19 patients. We found a high prevalence of various late effects in survivors of high-risk neuroblastoma using a non–TBI-based regimen including 3 cycles of high-dose therapy with ASCTs. As current treatment regimens recommend tandem ASCT without TBI, it is imperative that we understand and monitor for the sequelae from these modalities.