Long‐term follow‐up of bone density, general and reproductive health in female survivors after treatment for haematological malignancies

Abstract

The purpose of this study was to assess the ovarian function, fertility and bone mineral density in women who previously had treatment for different haematological malignancies (HMs). The overall survival and cure rates of patients with HMs have improved dramatically. The treatment affects fertility and bone density. Fifty-two premenopausal women, from Stockholm region, were included in the study between 1998 and 2002, followed until 2011. The diagnoses were acute lymphoblastic leukaemia (n = 6), acute myeloid leukaemia (n = 10), chronic lymphocytic leukaemia (n = 1), chronic myeloid leukaemia (n = 12), Hodgkin lymphoma (n = 12) and non-Hodgkin lymphoma (n = 11). Before treatment, women without children (43/52), when possible, were offered fertility preservation options. The mean age at diagnosis was 27, at final evaluation 39 yr. Thirty-seven patients received HSCT; 26 allogeneic, 11 autologous. Before allogeneic HSCT, nineteen patients had myeloablative conditioning; seven had reduced-intensity conditioning. Eleven patients got total body irradiation. Eight patients were transplanted with grafts from an HLA-identical sibling donor, while 18 had unrelated donors. All women were in a menopausal state post-therapy. Hormone replacement therapy (HRT) was given, and bone mineral density (BMD) was measured every other year. The serum levels of parathyroid hormone (PTH), free and bound calcium was within normal range. BMD measurements showed a slight increase over time in the spine with a mean of 0.015 g/cm(2) /yr. Four spontaneous pregnancies resulted in two babies and two discontinued pregnancies; two pregnancies were achieved with oocyte donation and surrogacy and one woman adopted a child. HRT sustains BMD in long-term survivors from HMs. This study highlights the importance of HRT and fertility issues in this patient group.

Fertility in female cancer survivors: a systematic review and meta-analysis

“…After review of the titles and abstracts, 41 studies were identified as potentially eligible for inclusion. After full review, four systematic reviews were excluded (Levine et al, 2015;Lopategui et al, 2017;van Dorp et al, 2016;Burkart et al, 2019), one publication because data could not be extracted (Zynda et al, 2012), 15 original studies because of the absence of a healthy control group (Carter et al, 2006;Kiserud et al, 2007;Sudour et al, 2010;Speiser et al, 2011;Hamre et al, 2012;Hansen et al, 2013;Reinmuth et al, 2013;Shepherd et al, 2006;Greaves et al, 2014;Naessén et al, 2014;Hoshi et al, 2015;Wu et al, 2015;Yonemoto et al, 2016;Shandley et al, 2017;Nichols et al, 2018) and three additional studies because they generically referred to reproductive prognosis after cancer without splitting data for cancer subtypes (Green et al, 2009;Reulen et al, 2009;Dillon et al, 2013).…”

Transplantations of frozen-thawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria

“…Patients with leukemia are at high risk for transfer of malignant cells with the transplanted tissue (21). Yet early age at diagnosis and high ovarian failure rates after treatment put them at a high need for OTCP (22,23), especially as immediate chemotherapy is required on admission, precluding the use of other fertility preservation techniques (14). To provide maximal safety and avoid reintroduction of malignancy on transplantation, both postchemotherapy tissue harvesting and an intense search for leukemic cells were performed.…”

“…Neither of them were treated with chemotherapy before tissue collection. The use of the described approach significantly increases transplantation safety, potentially overcoming previous restrictions for transplantation (22,23).…”

Are Survivors of Childhood Acute Lymphoblastic Leukemia at Increased Risk for Low Bone Mass?

“…Firstly, this special and growing population have mixed health problems, habitually underwent multiple and different chemotherapy protocols (including myeloablative conditioning) and/or radiation treatment schedules (including TBI) previously to SCT, that might lead to decreased gonadal function and fertility, which is one of the most important factors in determining reduced BMD in these patients [40,58]. Secondly, after SCT these patients receive immunosuppressive regimens with glucocorticoids, and they might develop several complications, including graft-versus-host disease (GVHD), which requires additional long-term excessive dose of glucocorticoids, and consequently aggravate bone loss and the risk for AVN [58,59].…”