Elzbieta Leszczynska

Anti-Müllerian Hormone as a Sensitive Marker of Ovarian Function in Young Cancer Survivors

We evaluated ovarian function by measuring the levels of anti-Müllerian hormone (AMH), estradiol, and gonadotropins in 83 young women treated for cancer during childhood and adolescence, and classified according to post-treatment gonadal toxicity versus 38 healthy females. Results. The mean AMH values were lower in the entire cohort independently of the risk group as compared to the control, whereas FSH was elevated only in the high risk group. The lowest AMH values were noted in patients after bone marrow transplantation (BMT) and those treated for Hodgkin lymphoma (HL). Nineteen patients (22.9%) had elevated FSH. They all had low AMH values. Lowered AMH values (but with normal FSH and LH) were observed in 43 patients (51.8%). There was no effect of age at the time of treatment (before puberty, during or after puberty) on AMH levels. Conclusion. Our results show the utility of AMH measurement as a sensitive marker of a reduced ovarian reserve in young cancer survivors. Patients after BMT and patients treated for HL, independently of age at treatment (prepuberty or puberty), are at the highest risk of gonadal damage and early menopause.

The Progressive Reduction in the Ovarian Reserve in Young Women After Anticancer Treatment

Anticancer treatment can disturb gonadal function and deplete the primordial follicle pool, leading to premature menopause. We made a prospective analysis of serum hormone levels in young female cancer survivors who had been treated during childhood and adolescence. Serum anti-Müllerian hormone (AMH) as a marker of ovarian reserve, FSH, LH, and estradiol were measured in 33 women treated previously (6-11 years earlier) for Hodgkin Lymphoma, solid tumours, and after bone marrow transplantation, and in 34 healthy controls. The group of survivors was divided according to the risk of gonadotoxicity into the low risk and median risk group (LR+MR), and into the high risk (HR) group. The measurements were repeated after 5 years. In the HR group, AMH levels were significantly lower than in controls (p=0.001) and in the LR+MR group (p=0.006) at the time of the first examination fell progressively after 5 years (p=0.03), whereas elevated FSH values (p=0.053) increased (p=0.001). Unchanged LH values in the first measurement rose in the second one (p=0.001). In the LR+MR group, the levels of AMH and FSH were normal (compared to the control) at baseline, but after 5 years serum AMH decreased (p=0.027) and FSH increased (p=0.008). Our findings indicate that anticancer treatment during childhood and adolescence is associated with a serious, progressive risk of ovarian failure. It is necessary to inform female cancer survivors, especially the high risk patients, about the risk of premature menopause.

Influence of Iron Overload on Immunosuppressive Therapy in Children with Severe Aplastic Anemia

Children with severe aplastic anemia (AA) require multiple transfusions of the red blood cells during the immunosuppressive therapy. This leads to iron overload and manifests as elevated levels of ferritin in blood. The aim of this study was a retrospective analysis of the influence of the elevated serum ferritin on the overall survival, event-free survival, the risk of relapse, and response to treatment in children with AA during immunosuppressive therapy. We analyzed 38 children with AA (19 girls, 19 boys, aged 2-17 years) treated according to the obligatory protocol for AA in Poland. The response rate was assessed on days 84, 112, and 360. Patients were divided into three groups: group I consisted of children with ferritin below 285 ng/mL (6 children), group II with ferritin between 286 and 1,000 ng/mL (13 children), and group III ferritin>1,000 ng/mL (19 children). Kaplan-Meier plot was used to estimate the overall survival and event-free survival. We found the overall survival did not differ between the three groups. Event-free survival was significantly shorter (p=0.03) in patients with ferritin levels>1,000 ng/mL compared with the groups with ferritin bellow 1,000 ng/mL. The time to relapse was significantly shorter in group III than in the other two groups (p=0.02). We also found the differences in the treatment response at day 84 (p=0.03) and day 112 (p<0.0001) of immunosuppressive therapy. These findings confirm a negative influence of iron overload in children with AA on the effect of treatment and the risk of relapse.

First-line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

Proteasome chymotrypsin-like activity in plasma as a useful marker for children with acute lymphoblastic leukemia

Abstract Background. The proteasome chymotrypsin-like (Cht-L) activity was determined in plasma of children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in correlation to baseline leukocytosis, immunophenotype, LDH at the time of diagnosis and after remission induction. Procedure. The activity was assayed using the fluorogenic peptide substrate in the presence of an artificial activator sodium dodecyl sulfate (SDS) in the plasma of healthy donors (n=25), acute lymphoblastic leukemia, ALL (n=95) and AML (n=17) patients. Results. As compared to healthy subjects, the plasma proteasome ChT-L activity was significantly increased (p=0.001) in ALL patients prior to treatment, especially in those with T-ALL immunophenotype and with high LDH activity. Similarly, in AML patients the plasma proteasome ChT-L activity was elevated (p=0.001). Following remission-inducing chemotherapy, the activity of the ChT-L proteasome was significantly reduced both in ALL and AML patients. Conclusion. Plasma proteasome ChT-L activity may serve as an additional marker in monitoring anticancer therapy.

Improvement of cure after hematopoietic stem cel transplantations in children

Wstep. Transplantacja komorek krwiotworczych (HSCT) jest wazną metodą terapeutyczną w wielu wrodzonych i nabytych chorobach, w tym nowotworowych, zespolach niewydolności szpiku oraz zaburzeniach immunologicznych i metabolicznych. Celem pracy jest analiza wynikow HSCT w pojedynczym ośrodku pediatrycznym w okresie 12 lat. Pacjenci i metodyka. Analizie poddano wyniki przeszczepien wykonanych w latach 2003-2015 w Klinice Pediatrii, Hematologii i Onkologii w Bydgoszczy. Transplantacje analizowano w trzech przedzialach czasowych: 2004-2007, 2008-2011 oraz 2012-2015. Wyniki. Wykonano 318 HSCT, w tym 186 alloge-nicznych (68 zgodnych rodzinnych i 118 od dawcow alternatywnych) oraz 132 autologiczne. Średnie przezycie po HSCT, wyznaczone metodą Kaplana-Meiera wynioslo 8,1 lat. Calkowite prawdopodobienstwo przezycia (pOS) wynioslo 0,64±0,03; pOS po allo-HSCT wynosi 0,62±0,04, a po auto-HSCT 0,67±0,05. Nie wykazano znamiennych roznic w pOS zarowno po allo-HSCT, jak i po auto-HSCT pomiedzy drugim (2008-2011) i trzecim (2012-2015) analizowanym okresie. Jednakze, pOS bylo wyzsze w dru-gim i trzecim okresie w stosunku do okresu pierwszego (2004-2007), zarowno dla wszystkich pacjentow, jak i u pacjentow po auto-HSCT. W grupie pacjentow allo-HSCT, uzyskano wzrost pOS o ponad 20% (43% vs 66% vs 64% w kolejnych przedzialach czasu; ns). Wnioski. Wyniki HSCT uzyskiwane aktualnie w na-szym ośrodku są porownywalne z wynikami podawanymi w miedzynarodowych rejestrach.