Background: Family planning is important in patients (pts) with chronic myeloid leukemia (CML) who can have a near normal lifespan in tyrosine kinase inhibitors (TKI) era. Management of CML on conceptions and pregnancies is not defined as cases are rare and data are scarce. To investigate this issue a multicenter retrospective and prospective observational study of conception/pregnancy in CML pts was initiated within the European LeukemiaNet (ELN) from February 2014 till present. All ELN centers and participants from other countries were invited and received the study's protocol which was adopted in agreement with specific national laws. Aims: The main goal was to describe CML pts in terms of pregnancy/conceptions management and outcome. Secondary goals included demographics, characteristics of CML, management during pregnancy, pregnancy outcomes and characteristics of children. Methods: Adult pts aged ≥18 years with Ph+ positive CML and pregnancy were included after signing a written informed consent. Data were collected either in the coordinating centers in Moscow (Russia) and Rome (Italy) followed by the analyses of the entire data set. A total 305 pregnancy cases in 234 CML female pts from 15 centers of 13 countries worldwide were analyzed (Table 1). Results: Chronic phase at diagnosis was in 217/221(98%) pts. In 50 (21%) pts CML was diagnosed during pregnancy, while 184 (67%) got pregnant after diagnosis. Median (Me) time from CML diagnosis to pregnancy was 59 months (range 1–203). The outcomes of 305 pregnancies were as follows: labor 234 (77%), induced abortion 42 (14%), spontaneous abortion 21 (7%) and ongoing pregnancy or unknown outcome 8 (2%). Labor at full term was in 141 (75%) of 187 cases fully reported (Table 2). Molecular response (MR) evaluations at the start of pregnancy were recorded in 249/305 cases. Deep MR (DMR or BCR-ABL≤0,01% IS), major MR (MMR or BCR-ABL≤0,1%> >0,01% IS), MR2 (BCR-ABL>0,1%> ≤1% IS) and no MR2 (BCR-ABL>1% IS) was observed in 80 (32%), 31 (12%), 32 (13%) and 106 (43%) cases respectively. In 182 (71%) of 257 pregnancies with known data pts conceived while on TKI: 77% under imatinib (IM) and 23% TKI 2nd/3rd generation. TKIs were usually stopped early in 1st trimester (4–5 week of gestation) when the pregnancy was discovered. In 82 pregnancies pts were treated during 2nd-3rd trimester, after placental formation, until labor with IM: 33 (40%) of cases), nilotinib (NIL): 8 (9%), interferon (IFN): 23 (28%, 1 PEG-IFN), hydroxyurea: 6 (7%). IM was used throughout pregnancy in 13 (16%). One case of leukaferesis was recorded. The number of born children in 226 fully reported labors was 233 (including twins). Congenital abnormalities were recorded in 4 (1,7%) cases as follows: polydactyly (1), hypospadias (1) and non-closed foramen ovale of interatrial septum (2). None of the abnormalities were severe or life threatening, relationship to TKI use was considered unlikely by physicians. Low birth weight was recorded in 13 children with IM or NIL exposure at late pregnancy. The follow-up of all children was uneventful, with Me age at follow-up of 5 years (range 2 months-17 years).Summary/Conclusion: Most pregnancies in CML female pts resulted in normal childbirth with no increased rate of birth abnormalities in spite of TKI use at conception even if treatments were mostly early stopped at implant (4–5 weeks). Different therapies were used during pregnancy when needed. The results in terms of conception/pregnancy may be valuable for the development of CML treatment schemes particularly considering the variety of disease status.
Abstract The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35–59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.
Abstract 1118 Poster Board I-140 Background The median age of an unselected population of Ph+ CML patients is close to 60 years. In the prognostic classifications (Sokal, Blood 1984; Hasford, JNCI 1998) that were elaborated before the introduction of IM, age was a significant and important prognostic factor. The most recent IM studies have not clarified the prognostic importance of age and IM therapy is still denied to several elderly patients. Aim to asses the relationship between age (less and more than 65 years) and outcome, in CML patients treated front-line in early chronic phase (ECP). Methods We analyzed the data of 559 previously untreated ECP patients who were assigned to receive IM 400 mg daily (76%) or 800 mg daily (24%) in three controlled, prospective studies of GIMEMA (Clin Trials Gov. NCT00514488 and NCT00510926; and an observational study of IM 400 mg). The median follow-up is currently 42 (extremes 1 – 64) months. There were 115 patients more than 65 years old (median age 71 years), while 444 (79%) were less than 65 years (median age 46 years). The proportion of patients who were treated with IM 800 mg daily was the same in both age groups. Results The cumulative complete cytogenetic and major molecular response rates were identical in the two age groups (88% vs 88% and 82% vs 83%, respectively). However, overall survival (86% vs 93%, p = 0.01), failure-free survival (72% vs 81%, p=0.03) and particularly event-free survival (calculated based on the intention-to-treat principle, where events were any failure [according to the European LeukemiaNet criteria – Baccarani, Blood 2006] and treatment discontinuation for any cause) (60% vs 71%, p=0.006) were significantly inferior in the older age group. All these difference were mainly due to comorbidities leading to more deaths in CP (table). Conclusions/Methods These data show that response to IM was not affected by old age. Survival curves were affected because of age-related complications and comorbidities. Age should never be a contraindication to IM treatment. Acknowledgements: European LeukemiaNet, COFIN, University of Bologna and BolognAIL. Disclosures Saglio: Novartis: Honoraria. Baccarani: Novartis Pharma: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Mayer Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau.
doi:10.1182/blood-2011-01-330563Prepublished online July 1, 2011;2011 118: 2069-2076€€€€Mieloproliferative (AGIMM) investigatorsBarbui, Alessandro M. Vannucchi and on behalf of the AIRC-Gruppo Italiano MalattieEmilio Usala, Ubaldo Occhini, Alberto Grossi, Silvia Caglio, Simona Paratore, Alberto Bosi, Tiziano Finazzi, Alessandro Pancrazzi, Elisabetta Antonioli, Maria Chiara Susini, Lisa Pieri, Elisa Malevolti,Lorenzo Tozzi, Flavia Biamonte, Niccolo Bartalucci, Elisabetta Gattoni, Maria Letizia Lupo, Guido Paola Guglielmelli, Giovanni Barosi, Alessandro Rambaldi, Roberto Marchioli, Arianna Masciulli,€
