12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
ALL CR2(2), MDS(1), secondary MDS post AML(2), blast crisis CML(2).
Most patients were heavily pre-treated and 5 had previous TBI containing
transplants (3 autografts, 2 allografts). Two had significantly low
transfer factor pre-transplant (DLCO less than 60% predicted) and two
patients had previous confirmed invasive fungal infections. The donors
were 4 matched sibling, 1 mismatched sibling and 7 matched unrelated
with PBSC used in 9 transplants; median CD34 dose 6.8 ×10 6 CD34/kg
(range 1.17 to 11.48) and BM in 3; median mononuclear dose 3.25 × 10 8
mononuclear cells/kg (range 2.65 to 4.32). Results. Toxicities were limited
with maximum Grade II mucositis and no patient required continuous
opiate infusion. Renal and hepatic toxicity was minimal and thought
to be unrelated to the regimen. There were no cases of VOD. The median
length of stay was 42 days (range 23 to 50). 11/12 patients engrafted
(1 developed RSV at Day +10 and subsequently died) with median time
to platelet recovery >20×10 9 /L Day +13, >50 ×10 9 /L Day +17, neutrophils
>0.5×10 6 /L Day +19, >1×10 6 /L Day +21. One patient developed acute
graft rejection within 100 days. Two patients had evidence of mixed
lymphoid chimerism. One has received DLI with resolution and neither
has relapsed. The incidence of acute GVHD was low with only Grade
1 skin involvement in 4 patients. One patient has developed severe
extensive chronic GvHD requiring long term immunosuppression. Three
patients have relapsed and 2 have died, the third remains alive in remission
with extensive chronic GVHD four years after DLI. The non-relapse
mortality at D100 was 8% (1/12) with an overall survival at 1 year of
75%. The regimen has been well tolerated with a mean Karnovsky score
at Day 100 of 70% and at 1 year 90%. Conclusions. We found this conditioning
regimen to be well tolerated with acceptable levels of toxicity
in high risk patients without compromising engraftment or increasing
relapse rates to unacceptable levels. We suggest consideration of this
regimen for patients who are at high risk of relapse and for whom a TBI
containing myeloablative regimen is unsuitable due to co-morbidity or
previous radiotherapy.
1249
OCCURRENCE OF EBV INDUCED B CELLS LYMPHOMA IN TWO PATIENTS TREATED
CONCOMITANTLY WITH FLUDARABINE, CYCLOPHOSPHAMIDE AND ALEMTUZUMAB
S. Rigaudeau, 1 C. Copie-Bergman, 2 F. Boidart, 1 I. Garcia, 1 A.L. Taksin, 1
M. Harzic, 1 S. Ghez, 1 F. Merabet, 1 P. Rousselot, 1 P. Gaulard, 2
S. Castaigne1 1 2 CHV André Mignot, LE CHESNAY, France; Hopital Henri Mondor,
CRÉTEIL, France
Because of strong immunosuppression, Epstein Barr Virus (EBV) positive
lymphoproliferative disorders (LPD) are frequently observed in HIV
patients or after transplantation. EBV+ LPD have been reported after
treatment of low-grade lymphomas or chronic lymphocytic leukaemia
(CLL) with Fludarabine. We report here two cases of an EBV+ LPD
occurring after the use of Fludarabine, Cyclophosphamide and Alemtuzumab.
A 68 year-old man had a diagnosis of B CLL (Matutes score
4/5) with a del 11 q on conventional cytogenetic analysis of peripheral
blood lymphocytes. He was treated with 5 courses of oral Fludarabine
(50 mg/day D1-D3) and Cyclophosphamide (400 mg/day D1-D3) from
September 2003 to February 2004 with good response. He relapsed in
April 2006 with multiple peripheral lymph nodes and splenomegaly.
Cytological examination of lymph nodes showed features of CLL with
no large cells. Total lymphocytes count was 1090/mm 3 . He received 9
weekly subcutaneous injections of Alemtuzumab (30 mg/injection). In
June 2006, erythroblastopenia and acute hepatitis occurred and a parvovirus
B19 infection was diagnosed. He received intravenous
immunoglobulins. Treatment with Alemtuzumab was stopped. In January
2007, high fever, abdominal pain, night sweats and blood analysis
consistent with an haemophagocytic syndrome appeared. Computed
tomographic scan showed hepatosplenomegaly and multiple abdominal
enlarged lymph nodes . The detection of EBV by PCR analysis was
positive in the serum. A lymph node biopsy showed features of EBV +
CD20 + Hodgkin-like lymphoproliferative disorder consistent with the
diagnosis of EBV induced B cell lymphoma. The patient is now treated
with Rituximab and CHVP with a good response. A 68 year-old man had
in 2004 a diagnosis of T prolymphocytic leukaemia without clinical
symptoms nor tumoral syndrome. He was untreated until 2005 when
he was referred to our center with major asthenia, hepato-splenomegaly,
pleural effusion and ascitis; total lymphocytes count was 108 000/mm 3 .
Immunophenotype revealed T lymphocytes CD3 + CD4 + CD52 + . A
course of CHOP was unsuccessful and treatment with oral Fludarabine
(50 mg/d D1-D3), oral Cyclophosphamide (600 mg/d D1-D3) and Alemtuzumab
(30 mg/injection) was started in February 2006. He received a
total of 8 monthly courses of Fludarabine and Cyclophosphamide and
454 | haematologica/the hematology journal | 2007; 92(s1)
Alemtuzumab by subcutaneous injections at a dose of 30 mg times 3
weekly for 4 months, then once per month for 6 months. In December
2006 he noted an enlarged cervical lymph node. Fever, night sweats,
and serum analysis were consistent with an hemophagocytic syndrome.
Histological examination of the cervical lymph node showed features of
EBV+ diffuse large B cell lymphoma consistent with the diagnosis of EBV
induced B cell lymphoma. The patient is currently treated with Rituximab
and CHOP. These two cases are different by the initial pathology
and the way of administration of Fludarabine, Cyclophosphamide and
Alemtuzumab. Nevertheless they emphasize the risk of EBV induced
lymphoma in severe immunodeficient patients. The concomitant use of
three immunosuppressive agents must be weighted carefully. The monitoring
of EBV viral load in serum should be performed routinely as is
done the measure of cytomegalovirus viral load .
1250
FROM STEM CELLS TO CIRCULATING BLOOD: DYNAMIC AND ARCHITECTURAL ASPECTS
OF HEMATOPOIESIS
D. Dingli, 1 A. Traulsen, 2 J.M. Pacheco3 1 Mayo Clinic, ROCHESTER, USA; 2 Harvard University, CAMBRIDGE,
USA; 3 University of Lisbon, LISBON, Portugal
Background. Circulating blood cells undergo continuous cell turnover
and are constantly being produced within the bone marrow in the
process of hematopoiesis. At the root of blood cell formation are the
hematopoietic stem cells (HSC). Recently, it was shown that the size of
the active HSC pool is small (~400 cells in adult humans) and these cells
replicate at a very slow rate (~1/year). In contrast, the average marrow
output of ~ cells per day in huge. To date, no simple model has been able
to capture the essential features of the scaling in time and population that
characterize hematopoiesis. Aims. To develop a testable model that can
account for the amplification and differentiation of blood cell formation
over such a wide range of time scales. Methods. We consider that
hematopoiesis is divided into compartments where cells in any compartment
i divide to produce 2 daughter cells. The two cells either differentiate
(with probability ?) and move to the next compartment (i+1) or,
with probability (1-?), remain in compartment i for amplification of that
compartment. Cells lost from compartment i, are replaced by cells from
compartment i-1 so that the population within each compartment
remains constant under stationary conditions. We utilize data from granulocyte
production to calibrate the model. Results. Our model predicts
that there are at least 31 amplification and differentiation steps between
the active HSC pool and circulating blood cells. In any given compartment,
meaning that in general, cells in any compartment differentiate
and move to the next compartment downstream rather than self-renew.
The model predicts the size and the replication rate of cells within any
compartment. When tested on the limited data available for PIG-A
mutant cells in the circulation, the model accurately predicted the average
life duration of these clones in healthy adults. Summary/Conclusions.
Hematopoiesis can be visualized as a series of cell filled compartments
where amplification and differentiation occur. Blood production is due
to an exponential increase in the number of cells due to increasingly
rapid replication rates as differentiation occurs. The model makes predictions
that agree closely with the limited data available in the literature.
The model can be utilized to gain insights into various hematopoietic
disorders and such studies are underway.
1251
HIGH SERUM FERRITIN LEVEL IS AN IMPORTANT PREDICTIVE FACTOR FOR POOR
STEM CELL MOBILIZATION IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES
M. Yoo Hong, H.W. Lee, I.H. Park, S.H. Yoon, S.J. Kim, D.Y. Hwang,
Y.R. Kim, J.S. Kim, J.W. Cheong
Yonsei University College of Medicine, SEOUL, South-Korea
Background. Iron overload presented by high level of serum ferritin is
often observed in various hematologic diseases. Iron overload has some
negative effect on engraftment and survival after hematopoietic stem cell
transplantation. Aims. We analyzed the effect of transfusional iron overload
in patients with hematologic malignancy on mobilization of CD34 +
cells. Methods. We evaluated 50 patients, 18 (36%) with multiple myeloma,
25 (50%) with malignant lymphoma and 7 (14%) with AML. Median
duration from diagnosis to stem cell collection is 166 days (range, 27
- 484 days) and mean number of packed RBC transfusion is 4.8 unit
(range, 0 - 20 units). Iron overload is defined that serum ferritin level is
>1000 ng/mL. The patients with non-transfusional hyperferritinemia
were excluded. Results. Fifteen patients (30%) were considered iron over-