Second solid cancers after allogeneic hematopoietic stem cell transplantation

Abstract

The specific roles of classical cadherins at key morphogenetic events during development are still not fully understood. As part of a project to study cadherin function during early mammalian development, we generated mice carrying an HA‐epitope tagged Cdh1 (E‐cadherin) cDNA knocked into the Cdh1 locus, similar to the previously described mouse mutants in which we forced Cdh2 (N‐cadherin) expression in the Cdh1 expression domain. As expected and in contrast to Cdh1Cdh2/Cdh2 and Cdh1−/−, our Cdh1HA/HA mutant embryos form proper trophectoderm, implant and undergo both gastrulation and neurulation. However, Cdh1HA/HA mice display an unexpected phenotype at embryonic day 10.5. Cdh1HA/HA embryos are smaller, paler and suffer from an insufficient nutrient supply. We detected a reduced expression of Cdh1HA specifically in the extraembryonic ectoderm and in the labyrinth layer, whereas expression in the embryo proper was normal. With this approach, we show for the first time that Cdh1 is essential for the correct formation of the placenta. Placentas without Cdh1 expression are impaired and incapable of establishing a proper connection between the embryonic and the maternal blood vessels for efficient nutrient and oxygen transport. Developmental Dynamics 239:2330–2344, 2010. © 2010 Wiley‐Liss, Inc.

Subsequent Malignant Neoplasms After Hematopoietic Cell Transplantation

“…The reported cumulative incidence of solid cancers following allogeneic SCT ranges from, 1.2% to 1.6% at 5 years, 2.2 to 6.1% at 10 years and from 3.8 to 14.9% at 15 years post transplantation (1,2,4,(20)(21)(22)(23)(24). There is no evidence for any plateau in the incidence rate (4); rather the slope of the curve continues to show a steadily increased incidence with increased follow-up.…”

Primary distal femur T-cell lymphoma after allogeneic haematopoietic stem cell transplantation for chronic myeloid leukaemia: A rare case report and literature review

“…22 Moreover, transplant recipients seem to have a higher risk of developing secondary cancers if the stem cells come from a female donor. 23 The patient described in this present case report was diagnosed with primary CML and never received treatment with imatinib. He received allo-HSCT and a conditioning regimen that contained fludarabine, busulfan, cytarabine and cyclophosphamide, which could have increased his risk for subsequent PTLD.…”

Second cancers early post allogeneic transplant: the case of ‘unrestrained’ malignancy?

“…Reported carcinomas include glioblastoma, squamous cell carcinoma (oral-cavity, skin, vulva), melanoma, basal cell carcinoma, ovarian, gastric and renal carcinomas as well as adenocarcinoma of the lung, liver and rectum. [1][2][3][4][5][6] New epithelial malignancies within o6 months are, however, exceptionally rare. Upon our review of the literature only eight such cases were identified: lung (2), stomach (2), renal (1), ovarian (1) and colon (2).…”

“…Upon our review of the literature only eight such cases were identified: lung (2), stomach (2), renal (1), ovarian (1) and colon (2). [4][5][6][7][8] Second cancers after transplant are usually recipientderived, but there are cases of donor origin. A recent review of donor-derived second malignancies after HSCT reported 11 such cases published, these included cases of invasive breast adenocarcinoma (1), oral squamous cell carcinoma (7), lung squamous cell carcinoma (1), Kaposi's sarcoma (1) and glioblastoma multiforme (1) occurring at an average of 7.9 (range 1-22) years after HSCT.…”