Tumori emopoietici in gravidanza Alessandro Rambaldi Ematologia

Tumori emopoietici in gravidanza
Alessandro Rambaldi
Ematologia
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo
Caravaggio, 17-5-2013
Hematologic malignancies in pregnancy
INCIDENCE
• The incidence of hematologic malingnancie in pregnancy
range from 1:1,000 to 1:10,000
MOST FREQUENT TYPES
• Hodgkin’s disease
• Leukemia
HODGKIN’S DISEASE
• A neoplasm of lymphoid tissue, derived from
germinal center B lymphocytes
• defined by the presence of the malignant
Hodgkin and Reed-Sternberg
CLASSIFICATION
CLASSIC HODGKIN LYMPHOMA (95%):
Nodular sclerosis
Mixed cellularity
Lymphocyte-rich
Lymphocyte-depleted
NODULAR LYMPHOCYTE-PREDOMINANT
Hodgkin’s disease in pregnancy
Incidence: is not uncommon 1:1,000 to 1:6,000.
Diagnostic Workup
1. Clinical history searching for B symptoms or other symptomatic
problems suggesting more advanced disease
2. Physical examination for lymphadenopathy or organomegaly
3. Complete blood cell counts and biochemistry
4. Chest radiograph (PA view only) with appropriate shielding
5. Abdominal ultrasound for retroperitoneal lymphadenopathy
6. Other tests required only for specific Hodgkin lymphoma
presentations
2-years FFS
1
0,9
0,8
p Log-Rank test < 0.001
0,7
0,6
0,5
PET2pos
2 -y FFS 82,67%
0,4
PET2neg
2 -y FFS 96,88%
PET2tot
2 -y FFS 94,82%
0,3
ABVD 1°-2°: RDI 98.2%
ABVD 3°-6: RDI 95.1%
(R) BEACOPP: RDI 84.3%
0,2
0,1
0
PET2neg
PET2pos
PET2tot
0
90
189 (0)
32 (0)
221 (0)
189 (0)
32 (0)
221 (0)
Gallamini, ASH 2012
180
189 (0)
32 (1)
221 (1)
270
189 (1)
31 (1)
220 (2)
360
187 (0)
30 (1)
217 (1)
450
540
630
720
185 (1)
29 (0)
214 (1)
174 (1)
28 (1)
202 (2)
148 (2)
20 (1)
168 (3)
121 (1)
17 (1)
138 (2)
Treatment of Hodgkin’s disease in pregnancy
1. The majority of patients found to have Hodgkin lymphoma
during pregnancy require no immediate intervention
2. Radiation or chemotherapy should be avoided during the first
trimester unless severely threatening symptoms are present
3. Asymptomatic or minimally symptomatic patients can be
followed through the entire pregnancy without treatment,
which can be reserved for development of symptomatic or
threatening disease
4. More than 50% of patients can continue the pregnancy to
term without any treatment for the lymphoma
Treatment of Hodgkin’s disease in pregnancy
(If symptomatic or threatening disease develops)
1. Radiotherapy during pregnancy may have deleterious effects on
the fetus due to direct or scatter irradiation, which may not be
evident until many years later
2. Single-agent chemotherapy should be considered. Vinblastine,
first described for this use >40 years ago, is particularly
attractive because of its high effectiveness against Hodgkin
lymphoma (> 75% response rate) and modest acute toxicity
3. ABVD has been used during pregnancy, and no obvious negative
effects on the fetus have been identified
Treatment of Hodgkin’s disease in pregnancy
(Summary)
1. Watch and wait
2. If needed (large tumor masses) steroids can be used
3. Avoid chemotherapy during the first 16 weeks of pregnancy
4. If needed, Vinblastine alone or ABVD recommended
5. Abortion not indicated
Prognosis of Hodgkin’s disease in pregnancy
no effect of pregnancy on survival of women with HD
the induction of labour should be performed when there is a
viable fetus and mother’s count blood are not compromised
FETAL CONSEQUENCES
no risk for prematurity or intrauterine growth retardation
no reports of HD metastases to the placenta or fetus.
Leukemia in pregnancy
INCIDENCE
 very rare 1:100,000 annually
 acute 85-90%: 2/3 AML, 1/3 ALL
 chronic: CML 10%, rare CLL
CHARACTERISTICS
 same figures of those achieved in non pregnant women
 can affect pregnancy and the fetus
Prognosis of Acute Leukemias in pregnancy
PROGNOSIS
 Hematologic remission can be induced and achieved in 70-75%
 Survival depending on acute leukemia type
Acute Leukemias
Survival by risk group
at 5 years
favourable =10-20%
AML
t(8;21)
> 50-60% inv(16)
t(16;16)
t(15;17)
ALL
del(12p), t(12p),
highly hyperdiploid,
t(10;14)
t(14q11-q13)
Normal, other non-poor
20-40% del(5q), del(7q), +8,
del(9q), abn(11q23),
abn(12p), del(20q),
intermediate =50-70%
poor =20-30%
<20%
-5, -7, abn(3q), inv(3),
t(3;3), 21q, 17p, t(6;9),
t(6;11), t(9;22), complex
t(1;19), abn(9p),
del(6q)
t(9;22), t(4;11),
-7, +8, abn(11q23),
hypodiploid
Treatment of Acute Leukemias in pregnancy
the same of non pregnant women
therapeutic abortion in early gestation (teratogenic risk of
10% of CT in the first trimester)
standard treatment during second-third trimester
Acute promyelocytic leukaemia
AML:
FAB M3 / M3v
25% in latins
10% in anglo-saxons
D.I.C., haemorrhages
low WBC count
t(15;17) = PML-RARa
APL differentiation by ATRA
Avvisati G et al Blood 2011
APL in pregnancy
• A total of 42 cases from 35 articles. 12 first-trimester, 21 secondtrimester, and 9 third-trimester cases
• Most common treatment: (ATRA), anthracyclines, and
antimetabolites. Complete remission reported in 83%
• Administration of ATRA or chemotherapy in the first trimester was
associated with an increased risk of fetal malformations and
spontaneous abortion
• administration of ATRA and or chemotherapy in the second and
third trimesters was associated with relatively favorable fetal
outcomes
Yang D, Hladnik 2009
Sexual dysfunction and fertility in
long term survivors after HSC
transplantation
GITMO Trapianto Autologo
TRAPIANTI REGISTRATI (n=48592)
3228
3000
2856
2595
1809
2000
3130 3156 3136
2871
3033
2925
2866 2905
2475 2458
2414
2500
1756
1491
1500
1026
840
1000
580 616
426
500
ANNI
11
20
10
20
09
20
08
20
07
20
06
20
05
20
04
20
03
20
02
20
01
20
00
20
99
19
98
19
97
19
95
96
19
19
94
19
93
19
92
19
91
19
91
0
<1
9
N° TRAPIANTI REGISTRATI
3500
GITMO Trapianto Allogenico
Allotrapianti registrati
(N=25505)
2500
2073
2000
1598
14911491
14211449
1500
1056 1065
1000
1736
1316 1299
1214
885
669
500
1160
1684
368
443 471
742 785
531 558
ANNI
20
12
20
11
20
10
20
09
20
08
20
07
20
06
20
05
20
04
20
03
20
02
20
01
20
00
19
99
19
98
19
97
19
96
19
95
19
94
19
93
19
92
19
91
<1
99
1
0
GITMO Trapianto Allogenico
Tipo di trapianto
2000
HLA id. sib.
Fam. Mismatch /Aplo
MUD/CB
1506
1500
1380
1361
1340
N. TRAPIANTI
Fam. Match
1409
1352
1168
1209
1149
963
1000
736
701
509
500
414
294
247
107
87
330
291
57
54
37
51
0
2001-2002
2003-2004
2005-2006
2007-2008
ANNI
2009-2010
2011-2012
The adverse effect of the
conditioning regimen
Alkylating agents
- busulphan
- cyclophosphamide
- melphalan
Total Body Irradiation
EBMT LEWP
199 centres responded
- Total patients 37.362 (19.412 allo and 17.950 auto)
- Median follow up 6.5 years
- Total pregnancies 312
Patients 232 (0.6%)
Crude birth rate 1.7/1000/YEAR
BMT Survivor Study
Adverse predictors
1. age > 30 at transplant OR 4.8
2. female sex OR 3.0
3. Total body irradiation OR 3.3
Allo vs Auto
Conclusion
The problem….
• Sexual dysfunction and infertility are very
common after HSCT
…... The solution
• Collaborative efforts
`