Germ cell damage and Leydig cell insufficiency in recipients of nonmyeloablative transplantation for haematological malignancies.

Most bone marrow transplant recipients are infertile due to reversible or irreversible testicular failure. However, little is known about the gonadotoxic potential of the newly introduced nonmyeloablative transplants. We undertook a 24-month longitudinal study in a cohort of 32 recipients of nonmyeloablative transplantation to test whether the combined regimen of fludarabine, melphalan and CAMPATH-1H can induce damage to germ cell (GC) and Leydig cell (LC) compartments. Testicular function was assessed immediately prior to transplantation and at four time points post-transplant to compare hormonal levels before and after the procedure. Two other groups treated with BEAM- and TBI-related regimes were also included in the study group for comparative purposes. GC function was assessed by measuring basal serum follicle stimulating hormone (FSH). LC function was assessed by measuring basal luteinising hormone (LH) and testosterone (T) levels. LC reserve was assessed by measuring the T/LH ratio. As a group, patients who received a non myeloablative transplant sustained severe damage to the GC compartment, as evident from a substantial elevation in the FSH level post-transplant (12 IU/l vs 18.4 IU/l, P<0.001). Similar to the GC injury, patients as a group sustained significant damage to the LC compartment following the transplant (5.4 IU/l vs 9.6 IU/l, P<0.001). In general, patients had reduced LC reserve post-BMT, as evident from a diminished T/LH ratio (2.6 pretransplant vs 1.6 post-transplant P=0.05). Patients who received a nonmyeloablative transplant had a similar effect on the GC and LC compartments compared to those who had a BEAM autograft. On the other hand, patients who received a TBI-based transplant sustained more damage to their GC and LC compartments compared to those who received a nonmyeloblative transplant; however, this was not statistically significant (P=0.09). Our data suggest that this type of regimen is potentially gonadotoxic and consideration should be given to fertility counselling and testosterone replacement therapy post-transplant.

Patterns of Leydig cell insufficiency in adult males following bone marrow transplantation for haematological malignancies.

Gonadal and sexual function are key to quality of life following bone marrow transplantation (BMT), but no large studies have been published on Leydig cell (LC) function in adults. LC insufficiency (LCI) can cause premature andropause with its consequences including sexual morbidity from diminished libido and erectile dysfunction (ED). In addition, LCI can result in generalised fatigue and even osteopenia. We reviewed gonadal function pre-transplant (immediately prior to BMT) and at 3-18 months post BMT in 117 patients who underwent BMT for a variety of haematological malignancies. The patients presented with variable degrees of symptoms of LCI, such as fatigue, diminished sex drive and libido or ED. The results suggest that the patients sustained severe gonadal damage to both their germ cells (GC) as well as the LC compartment (P < 0.001). We characterised two distinct functional subsets of LC insufficiency: Type I: compensated type with high LH and normal T levels and low T/LH ratio: (n = 102); and type II: uncompensated type (premature andropause) with high LH and low testosterone levels with low T/LH ratio (n = 15). Although type II patients had more severe LC damage than type I, patients in both groups were symptomatic. We recommend that symptomatic patients in both groups may benefit from a therapeutic trial with testosterone replacement treatment (TRT) for 3-6 months.

Extended routine polymerase chain reaction surveillance and pre-emptive antiviral therapy for cytomegalovirus after allogeneic transplantation.

Pre-emptive treatment strategies based on sensitive screening for cytomegalovirus (CMV) infection up to day +100 after allogeneic transplantation have been shown to reduce the incidence of CMV disease during the period of surveillance. However, the use of ganciclovir has been associated with delays in immune reconstitution and an increased incidence of late CMV disease after day +100. In the present study, 81 patients undergoing allogeneic transplantation received polymerase chain reaction (PCR)-guided pre-emptive therapy based on detection of CMV DNA by PCR on 2 consecutive weeks up to day +180. Thirty-three of the 52 high-risk patients (CMV-seropositive donor or recipient) received a total of 45 treatment episodes up to day +100. Three of these patients (5.7%) developed CMV disease, with one fatality. Twelve of the surviving 44 high-risk patients (27%) required pre-emptive treatment between days +101 and +192, but none of these patients developed late CMV disease with a median follow-up of 402 d (range 117-952 d). Antiviral therapy was stopped after a single negative PCR result with no subsequent episodes of CMV disease while patients remained off antiviral treatment. As all initial episodes of CMV DNA detection occurred within 60 d of transplantation, it may be possible to discontinue monitoring beyond day +100 in patients who have remained CMV PCR negative before this. Thus, we have confirmed that PCR-guided pre-emptive therapy results in a low incidence of CMV disease before day +100 and that discontinuing treatment on the basis of viral clearance as determined by CMV PCR appears to be safe practice. In addition, we have observed no episodes of late CMV disease with an extension of surveillance to 26 weeks.

Care after bone marrow transplantation.

Assessments vital to the recovery of patients following bone marrow transplant are detailed in this article, and the protective environment in which they need to be nursed is outlined. Common infections and side effects are highlighted.