Hi Gabylon,
All right, I was able to work on this while my in-laws napped. Great things, naps!
What I've done is to assemble a set of 19 citations/abstracts that I
think will be of use to you. I searched the PubMed MEDLINE database
(www.pubmed.gov), as it contains more than 14 million records and is
the primary database for medicine. The articles I selected are
clinical trials, case studies, and a few letters (where researchers
will sometimes send in previews of ongoing research as a sort of claim
on the findings) using the following search as a basis:
"("Polycythemia Vera/drug therapy"[MeSH] OR "Polycythemia
Vera/radiotherapy"[MeSH] OR "Polycythemia Vera/rehabilitation"[MeSH]
OR "Polycythemia Vera/surgery"[MeSH] OR "Polycythemia
Vera/therapy"[MeSH]) Field: All Fields, Limits: Middle Aged + Aged:
45+ years, Publication Date from 1999 to 2004, English, Clinical
Trial, Male, Human"
I then played around with the limits a little in order to get some
articles I'd feared I'd missed. The initial set included six
articles; the final set you will see has 19.
I think the most "cutting edge" of these are probably numbers 2 and 3,
which deal with hematopoietic stem cell research and a drug called
imatinib mesylate. Both of these therapies are dealt with in other
articles as well. Also included are some other therapies that are
being evaluated for their long term efficacy, including low-dose
aspirin and pipobroman.
Most of these articles refer to each other and to other studies of
diagnosis and prognosis of PV from about the early-1990s to the
current time. You will see some articles from the 1960s through the
1980s cited - but I've noticed that everyone seems to reference a
fairly small group from that time. Those appear to be the standard
descriptive articles for PV (they have titles like "Complications and
causes of death in polycythemia vera") or lay out the therapies that
have been (or were) standard in the past.
The review article referenced by pafalafa in the clarification
section, above, is not bad if you're interested in an overview of
therapies for PV. However, I generally steer clear of reviews when
I'm trying to find out what the new studies are - it takes so long to
compile a review that the authors may miss things simply due to
timing.
Also remember that "cutting edge" is a tricky term. Part of the
reason citations in articles tend to be 2 years out of date (as it
were) is that it can take up to 2 years for an accepted paper to be
published in a good journal. That's a real pain, in my opinion.
Enough explanation, here are the articles. If you're interested in
particular ones, I'd suggest you visit your local academic or (better
yet) medical library to copy the articles. A lot of these are
available electronically, but if you don't have access to e-journals
through an academic or corporate institution it's much cheaper to
either make a hard copy or order them via the National Library of
Medicine's Loansome Doc service than it is to purchase them direct
from the publisher. I've included the PubMed ID number (PMID) with
each abstract so you have the unique identifier should you need it.
1: New England Journal of Medicine. 2004 Jan 8;350(2):114-24.
Comment in:
N Engl J Med. 2004 Apr 15;350(16):1683-5; author reply 1683-5.
N Engl J Med. 2004 Apr 15;350(16):1683-5; author reply 1683-5.
N Engl J Med. 2004 Apr 15;350(16):1683-5; author reply 1683-5.
N Engl J Med. 2004 Jan 8;350(2):99-101.
Efficacy and safety of low-dose aspirin in polycythemia vera.
Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T;
European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators.
BACKGROUND: The use of aspirin for the prevention of thrombotic complications in
polycythemia vera is controversial. METHODS: We enrolled 518 patients with
polycythemia vera, no clear indication for aspirin treatment, and no
contraindication to such treatment in a double-blind, placebo-controlled,
randomized trial to assess the safety and efficacy of prophylaxis with low-dose
aspirin (100 mg daily). The two primary end points were the cumulative rate of
nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular
causes and the cumulative rate of nonfatal myocardial infarction, nonfatal
stroke, pulmonary embolism, major venous thrombosis, or death from
cardiovascular causes. The mean duration of follow-up was about three years.
RESULTS: Treatment with aspirin, as compared with placebo, reduced the risk of
the combined end point of nonfatal myocardial infarction, nonfatal stroke, or
death from cardiovascular causes (relative risk, 0.41; 95 percent confidence
interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of
nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major
venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95
percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and
cardiovascular mortality were not reduced significantly. The incidence of major
bleeding episodes was not significantly increased in the aspirin group (relative
risk, 1.62; 95 percent confidence interval, 0.27 to 9.71). CONCLUSIONS: Low-dose
aspirin can safely prevent thrombotic complications in patients with
polycythemia vera who have no contraindications to such treatment. Copyright
2004 Massachusetts Medical Society
PMID: 14711910 [PubMed - indexed for MEDLINE]
2: Blood. 2003 Dec 1;102(12):3912-8. Epub 2003 Aug 14.
Allogeneic hematopoietic stem cell transplantation for myelofibrosis.
Deeg HJ, Gooley TA, Flowers ME, Sale GE, Slattery JT, Anasetti C, Chauncey TR,
Doney K, Georges GE, Kiem HP, Martin PJ, Petersdorf EW, Radich J, Sanders JE,
Sandmaier BM, Warren EH, Witherspoon RP, Storb R, Appelbaum FR.
Fifty-six patients, 10 to 66 years of age, with idiopathic myelofibrosis (IMF)
or end-stage polycythemia vera or essential thrombocythemia received allogeneic
hematopoietic cell transplants from related (n = 36) or unrelated (n = 20)
donors. Forty-four patients were prepared with busulfan plus cyclophosphamide
and 12 with total body irradiation plus chemotherapy. The source of stem cells
was marrow in 33 and peripheral blood in 23 patients. All but 3 patients
achieved engraftment. While 50 patients showed complete donor chimerism, 3
patients were found to be mixed chimeras at 26, 48, and 86 months after
transplantation, respectively. Two patients died from relapse/progressive
disease, and 18 died from other causes. There are 36 patients surviving at 0.5
to 11.6 (median, 2.8) years, for a 3-year Kaplan-Meier estimate of 58% (CI,
43%-73%). Dupriez score, cytogenetic abnormalities, and degree of marrow
fibrosis were the most significant risk factors for posttransplantation
mortality. Patients conditioned with a regimen of busulfan targeted to plasma
levels of 800 to 900 ng/mL plus cyclophosphamide had a higher probability of
survival (76% [CI, 62%-91%]) than other patients. Results with unrelated donors
were comparable with those with HLA-identical sibling transplants. Thus,
allogeneic hematopoietic cell transplantation offers long-term relapse-free
survival for patients with myelofibrosis.
PMID: 12920019 [PubMed - indexed for MEDLINE]
3: Blood. 2003 Sep 15;102(6):2240-2. Epub 2003 May 22.
Comment in:
Blood. 2004 Apr 15;103(8):3241; author reply 3241-2.
Imatinib mesylate inhibits autonomous erythropoiesis in patients with
polycythemia vera in vitro.
Oehler L, Jaeger E, Eser A, Sillaber C, Gisslinger H, Geissler K.
The overproduction of red blood cells in patients with polycythemia vera (PV) is
reflected in vitro by the formation of erythroid burst-forming units (BFU-Es) in
the absence of exogenous erythropoietin. In contrast to other myeloproliferative
disorders, the molecular mechanism of PV is unknown and no specific chromosomal
abnormality has been described. We speculated that imatinib mesylate may reverse
the pathological overproduction of red cells by inhibition of autonomous
erythropoiesis. In the present study, imatinib mesylate was found to either
block or strongly inhibit autonomous BFU-E formation in vitro in all patients
tested. Moreover, autonomous BFU-E growth was also markedly reduced by exposure
of PV cells to imatinib mesylate prior to cultivation in semisolid medium. The
profound effect of imatinib mesylate on autonomous erythropoiesis suggests the
involvement of an as yet unidentified kinase in the pathogenesis of PV and
should provide the rationale for a forthcoming clinical trial.
PMID: 12763928 [PubMed - indexed for MEDLINE]
4: Am J Med Sci. 2003 Mar;325(3):149-52.
Polycythemia vera responds to imatinib mesylate.
Jones CM, Dickinson TM.
We report 2 patients with polycythemia vera who were demonstrated to be
-negative and were unable to tolerate either hydroxyurea or interferon-alpha but
who had excellent clinical responses to imatinib mesylate (STI-571). This effect
is consistent with the inhibitory effect of imatinib mesylate on c-kit's
tyrosine kinase activity as demonstrated by its effectiveness in patients with
gastrointestinal stromal tumors.
PMID: 12640290 [PubMed - indexed for MEDLINE]
5: Haematologica. 2003 Mar;88(3):349-51.
Quantitative real-time polymerase chain reaction shows that treatment with
interferon reduces the initially upregulated PRV-1 expression in polycythemia
vera patients.
Fruehauf S, Topaly J, Villalobos M, Veldwijk MR, Laufs S, Ho AD.
PMID: 12651277 [PubMed - indexed for MEDLINE]
6: Cytotherapy. 2003;5(5):420-5.
Collection of autologous PBSC in patients with polycythemia vera.
Isola L, Gorsky M, Najfeld V, Scigliano E, Sinitsyna Y, Fruchtman S.
BACKGROUND: Allogeneic stem-cell transplantation (SCT) can eradicate
myelofibrosis (MF), but is limited by donor availability and toxicity. We
previously reported normalization of counts and resolution of MF after ablative,
syngeneic SCT in spent phase polycythemia vera (PV). Hence, GvL is not required
to eradicate MF. Autologous SCT may advance treatment for spent phase PV by
restoring effective hematopoiesis. The influence of organomegaly,
myelosuppression and MF on PBSC collection has not been studied in the setting
of PV. METHODS: Sixteen patients with PV underwent PBSC collection. Mobilization
was with filgrastim alone, with a target cell content of 2.5 x 10(6) CD34(+)/kg.
All myelosuppression was discontinued 2 weeks prior to collection. RESULTS:
Median ages at diagnosis and collection were 47 and 57 years, respectively.
Organomegaly, MF and use of myelosuppressive therapies were present in 10 (63%),
4 (25%) and 7 (44%) patients. Median total nucleated cells (TNC) and CD34(+)
counts were 8.3 x 10(8)/kg and 4.98 x 10(8)/kg. MF had an adverse effect on TNC
(p=0.05) but not on the CD34(+) content. Time from diagnosis and the use of
myelosuppresion had no influence on TNC and CD34(+) contents. Four patients had
CD34(+) contents <2.5 x 10(6)/kg. Complete blood count (CBC) parameters were not
predictive of CD34(+) content. DISCUSSION: Autologous PBSC collection is
feasible in PV several years after diagnosis. Organomegaly and MF are not
absolute contraindications for collection. Discontinuing myelosuppresion for 2
weeks before mobilization appears sufficient to collect adequate numbers of
CD34(+) progenitors.
PMID: 14578104 [PubMed - indexed for MEDLINE]
7: Hematology Journal. 2003;4(6):456-8.
Erythropoietic recovery during treatment with darbepoietin-alpha after impaired
rHuEPO response to anemia in two patients with osteomyelofibrosis after
peripheral blood stem cell transplantation.
Nguyen VA, Fauser AA, Basara N, Kiehl M.
PMID: 14671623 [PubMed - indexed for MEDLINE]
8: Hematology Journal. 2003;4(3):198-207.
Long-term outcomes of polycythemia vera patients treated with pipobroman as
initial therapy.
Kiladjian JJ, Gardin C, Renoux M, Bruno F, Bernard JF.
From 1968 to 1993, 179 newly diagnosed patients with polycythemia vera (PV) were
enrolled in a prospective study using pipobroman as first chemotherapy. Among
them, 140 fulfilled the Polycythemia Vera Study Group criteria for PV, and 39
patients (22%) can be considered as idiopathic erythrocytosis (IE). Vascular
events occurred in 10% of IE and 20% of PV patients and solid tumors in 7.7% of
IE and 12.8% of PV patients. There were no differences between PV and IE
patients with regard to progression to myelofibrosis (MF), leukemic events and
overall survival. Overall, 98.3% of patients initially responded to pipobroman,
with very mild toxicity. A total of 164 PV patients who received more than 1
year of pipobroman were analyzed for long-term evolution. The actuarial risk of
thrombosis was 15.6 and 23.8% at 10 and 18 years, respectively. In all, 21
patients developed a solid tumor during follow-up, added and/or switched drugs
being a risk factor. Actuarial risk of MF was as low as 4.9 and 9.4% at 10 and
15 years, respectively. Actuarial risk of leukemia was 14.4 and 18.7% at 10 and
15 years, respectively. Hyperleukocytosis at diagnosis was the only variable
significantly associated with higher risk of leukemia. The median survival was
15.5 years, with two initial adverse prognostic factors: age above 60 years and
hyperleukocytosis. Despite an increasing risk of leukemia with time, survival
was not lower when compared to the French matched population. Only age and
hyperleukocytosis at diagnosis were found to have a prognostic value in PV.
PMID: 12764352 [PubMed - indexed for MEDLINE]
9: International Journal of Hematology. 2002 Aug;76 Suppl 2:294-5.
Treatment of polycythemia vera with recombinant interferon.
Silver RT.
PMID: 12430940 [PubMed - indexed for MEDLINE]
10: Leukemia & Lymphoma. 2002 Jul;43(7):1409-14.
Curative therapy of advanced essential thrombocythemia or polycythemia vera by
hemopoietic stem cell transplantation.
Platzbecker U, Gooley T, Anasetti C, Appelbaum FR, Clurman B, Doney K, Chauncey
T, Flowers ME, Myerson D, Radich JP, Storb R, Witherspoon RP, Deeg HJ.
Twenty-five patients with advanced essential thrombocythemia (ET; n = 13) or
polycythemia vera (PV; n = 12) received hemopoietic stem cell transplants (HSCT)
at the Fred Hutchinson Cancer Research Center. In most cases the indication to
perform an HSCT was myelofibrosis with splenomegaly and peripheral blood
cytopenias or the development of a myelodysplastic syndrome (MDS) or acute
myeloid leukemia (AML). Patients were 18-60 (median 43) years old with intervals
from diagnosis to HSCT of 8-348 (median 168) months. All but five patients had
been treated with cytotoxic agents, and nine patients were splenectomized before
transplant. Conditioning was performed with chemotherapy only or chemotherapy
plus total body irradiation regimens followed by the infusion of either marrow
(n = 19) or peripheral blood stem cells (n = 6) from related (n = 16) or
unrelated (n = 9) donors. All evaluable patients showed sustained neutrophil
engraftment. Nine patients (seven with AML/MDS, two with myelofibrosis) died of
transplant-related complications, and 16 are surviving, 14 of them in continuous
unmaintained remission. With a median follow-up of 41 (range 5-116) months after
transplant, survival at 3 years is 64%. These data provide evidence that HSCT
can be a curative treatment for patients with advanced PV and ET.
PMID: 12389621 [PubMed - indexed for MEDLINE]
11: International Journal of Hematology. 2002 May;75(4):394-400.
Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera
and essential thrombocythemia: N- and K-ras mutations and microsatellite
instability in chromosomes 5 and 7 in 69 patients.
Mavrogianni D, Viniou N, Michali E, Terpos E, Meletis J, Vaiopoulos G,
Madzourani M, Pangalis G, Yataganas X, Loukopoulos D.
Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic
myeloproliferative diseases that carry intrinsically the potential for leukemic
transformation. The aims of this study were (1) to detect involvement of N- and
K-ras mutations in codons 12 and 13 in the pathogenesis of the chronic and
blastic phases of PV and ET, (2) to study the occurrence of microsatellite
instability (MSI) in chromosomes 5 and 7 during the chronic phase and blastic
transformation of the disease, and (3) to examine the incidence of leukemia in
patients treated with hydroxyurea (HU). Samples of PV and ET patients were
analyzed with a polymerase chain reaction. No N- or K-ras mutations were
detected. A positive score for MSI in chromosome 7 was found in 1 patient with
PV during leukemic transformation. Three of 69 patients developed acute
myelogenous leukemia, 2 with PV and 1 with ET. As of this report, the overall
incidence of leukemic transformation is 5.7% (2/35 patients) in PV and 3.3%
(1/30 patients) in ET patients treated with HU. These results indicate that (1)
MSI is a genetic marker that can be detected, even in a small group of patients,
at the blastic phase of the disease and (2) no increased leukemogenicity was
noted in this group of patients treated with HU.
PMID: 12041671 [PubMed - indexed for MEDLINE]
12: Acta Oncologica. 2002;41(1):50-5.
Symptoms, symptom distress and health-related quality of life in patients with
polycythaemia vera or essential thrombocythaemia during treatment with
interferon-alpha.
Merup M, Aberg W, Lofvenberg E, Svensson E, Engman K, Paul C, Gardulf A.
Sixteen patients with polycythaemia vera or essential thrombocythaemia were
treated with interferon-alpha in order to normalize elevated platelets. Patients
were followed for 6 months and the frequency and intensity of symptoms and side
effects were recorded before and during the study period by the patients and by
the doctor. Health-related quality of life was also assessed. The most
frequently reported pretreatment symptoms were fatigue, headache and muscle
pain. The intensity of fatigue initially increased during treatment and there
was no relief of any of the three most frequent symptoms during the treatment
period. Common interferon-related symptoms such as fever and chills were most
frequently reported after one week. After one month of treatment, symptoms
related to the gastrointestinal tract reached a peak. Two patients discontinued
treatment during the study period. Another patient suffered severe depression
after the study period when still on interferon. There was no difference between
the frequency of symptoms recorded by the doctor and that reported by the
patients.
PMID: 11990518 [PubMed - indexed for MEDLINE]
13: Leukemia & Lymphoma. 2001 Nov-Dec;42(6):1243-53.
Hydroxyurea-associated platelet count oscillations in polycythemia vera: a
report of four new cases and a review.
Steensma DP, Harrison CN, Tefferi A.
Cyclic oscillations in the peripheral blood platelet count were recently
described in two patients with polycythemia vera (PV) receiving therapy with
hydroxyurea (HU). This phenomenon can make proper HU dosing very challenging and
may be especially problematic in PV patients who are at risk for
thrombohemorrhagic complications. In this report, we describe four new cases of
HU-associated platelet oscillations in patients with PV and extend our
observations on one of the two previously reported cases. We also review cyclic
thrombocytosis within the broader context of periodic hematopoiesis. A
thrombopoietin-mediated negative feedback loop is central to most models of
periodic thrombopoiesis, but this is probably an oversimplification. It is
possible that HU destabilizes the delicate balance of thrombopoietin/c-Mpl
signaling in megakaryocytic lineage hematopoiesis that is already markedly
altered in PV; this hypothesis remains speculative. For patients who develop
oscillatory variation in their platelet counts associated with HU use, keeping
the HU dose constant may result in damping or termination of the cycles.
However, this strategy is not always successful.
PMID: 11911405 [PubMed - indexed for MEDLINE]
14: British Journal of Haematology. 2001 Feb;112(2):392-6.
Haemopoietic stem cell transplantation for advanced polycythaemia vera or
essential thrombocythaemia.
Jurado M, Deeg H, Gooley T, Anasetti C, Chauncey T, Flowers M, Myerson D, Storb
R, Appelbaum F.
Ten patients with polycythaemia vera (PV) and nine with essential
thrombocythaemia (ET) received a haemopoietic stem cell transplant (HSCT) at the
Fred Hutchinson Cancer Research Center between May 1988 and March 2000. HSCT was
performed because of progression to the spent phase of the disease with
myelofibrosis and splenomegaly in 10 patients and evolution into a
myelodysplastic syndrome (MDS) or acute myelogenous leukaemia (AML) in nine
patients. Patients were 18-59 years old (median 43). The interval from diagnosis
to HSCT was 77-300 months (median 170). Seven patients were splenectomized
before transplantation, and all but five had been treated with cytotoxic agents.
Eleven patients received a transplant from a related, and eight from an
unrelated, donor following conditioning with chemotherapy only or chemotherapy
plus total body irradiation regimens. All evaluable patients achieved sustained
engraftment. Twelve patients are surviving 5-116 months (median 41) after
transplant, 10 in continued complete remission, one in haematological remission
with residual marrow fibrosis and one with mixed haemopoietic chimaerism
currently receiving therapy with interferon. Seven patients (six with AML/MDS
and one with myelofibrosis) died of transplant-related complications. These data
show that HSCT can provide curative therapy for patients with PV and ET with
advanced disease.
PMID: 11167837 [PubMed - indexed for MEDLINE]
15: Neoplasma. 2001;48(5):389-92.
Leukemic transformation of polycythemia vera after treatment with hydroxyurea
with abnormalities of chromosome 17.
Tothova E, Fricova M, Stecova N, Hlebaskova M, Kafkova A, Raffac S, Guman T,
Svorcova E, Nebesnakova E.
The leukemogenic risk attributed to therapy of polycythemia vera with
radiophosphorus and alkylating drugs has led, over the last 20 years, to the
increased use of myelosupressive nonmutagenic drugs, especially hydroxyurea. But
there exist reports, which showed the development of polycythemia vera into
acute leukemia not only in patients treated with alkylating agents and
radiophosphorus but also with single hydroxyurea. In this article we present two
cases of polycythemia vera, in which the development to acute myeloblastic
leukemia occurred after long-term treatment with hydroxyurea. Significant is the
fact, that in both presented cases cytogenetic and FISH analysis showed
abnormalities of chromosome 17, in the one of case fullfilled criteria for
"17p-syndrome". Due to the possibility of leukemogenic potential in the time of
hydroxyurea treatment, it is necessary to be careful especially in young
patients. The dynamic follow up of cytogenetic analysis is necessary,
especially, in those, where long-term hydroxyurea therapy is supposed.
PMID: 11845984 [PubMed - indexed for MEDLINE]
16: Haematologica. 2000 Oct;85(10):1011-8.
Efficacy of pipobroman in the treatment of polycythemia vera: long-term results
in 163 patients.
Passamonti F, Brusamolino E, Lazzarino M, Barate C, Klersy C, Orlandi E,
Canevari A, Castelli G, Merante S, Bernasconi C.
BACKGROUND AND OBJECTIVES. Polycythemia vera (PV) is a myeloproliferative
disorder, characterized by the expansion of the red cell mass. Our purpose was
to evaluate the efficacy of pipobroman (PB) in the long-term control of PV and
to assess early and late events. DESIGN AND METHODS. From June 1975 to December
1997, 163 untreated patients with PV (median age 57 years, range 30-82) were
treated with PB in a single Institute for a median follow-up of 120 months. The
diagnosis was made according to the Polycythemia Vera Study Group criteria. PB
was given at the dose of 1 mg/kg/day until hematologic response (hematocrit <
45% and platelets < 400x109/L) and of 0.3-0.6 mg/kg/day as maintenance therapy.
RESULTS. Hematologic remission was achieved in 94% of patients in a median time
of 13 weeks (range 6-48). Median overall survival was 215 months, with a
standardized mortality ratio of 1.7. The cumulative risk of death was 11%, 22%,
and 26% at 7, 10, and 12 years, respectively. The incidence of thrombotic events
was 18.4x105 person-year and the cumulative risk was 6%, 11%, 16%, and 20% at 3,
7, 10, and 12 years respectively. Acute leukemia occurred in 11 patients,
myelofibrosis in 7, and solid tumors in 11. The 10-year cumulative risk of
leukemia, myelofibrosis, and solid tumors was 5%, 4%, and 8%, respectively. In
the logistic analysis age over 65 (p = 0.0001) and thrombotic events at
diagnosis (p = 0.001) were significantly correlated with a higher risk of death.
Female gender (p = 0.02) and age over 65 (p = 0.01) significantly influenced the
occurrence of thrombotic complications. Age was the only significant risk factor
for leukemia (p = 0.04) and for solid tumors (p = 0.03), while the duration of
PB treatment did not influence these risks. No significant risk factor was
demonstrated for myelofibrosis. INTERPRETATION AND CONCLUSIONS. This study
demonstrates in a large series of patients, observed for a long period, that
pipobroman is effective in the long-term control of PV. The risk of early
thrombotic complications at 3 years is 6% and the 10-year risk of acute
leukemia, late myelofibrosis, and solid tumors is 5%, 4%, and 8%, respectively.
The duration of pipobroman treatment did not correlate with these events.
PMID: 11025590 [PubMed - indexed for MEDLINE]
17: Blood. 2000 Aug 15;96(4):1582-4.
Hydroxyurea-induced marked oscillations of platelet counts in patients with
polycythemia vera.
Tefferi A, Elliott MA, Kao PC, Yoon S, El-Hemaidi I, Pearson TC.
Two prospectively studied patients with polycythemia vera (PV) whose platelet
counts showed marked periodic fluctuation during treatment with hydroxyurea (HU)
are reported. Cycle lengths in both were approximately 28 to 30 days. In one
patient, the cyclic process was no longer evident when treatment with HU was
withheld, and it reappeared on treatment rechallenge. Circulating thrombopoietin
(TPO) levels fluctuated out of phase with the platelet count despite markedly
reduced TPO-receptor (c-Mpl) expression in bone marrow megakaryocytes. These
observations suggest that the cyclic phenomenon may be related to both a
transient state of HU-induced depletion of megakaryocytes and a
concentration-dependent mitigation by TPO of the HU effect on megakaryocytes and
their precursors. It is conceivable that the affected patients harbor a
megakaryocyte progenitor pool whose apoptotic activity is differently modulated
by either HU or high concentrations of TPO. (Blood. 2000;96:1582-1584)
PMID: 10942409 [PubMed - indexed for MEDLINE]
18: European Journal of Haematology. 2000 Mar;64(3):188-93.
Hydroxyurea treatment reduces haematopoietic progenitor growth and CD34 positive
cells in polycythaemia vera and essential thrombocythaemia.
Andreasson B, Swolin B, Kutti J.
The aim of the present work was to investigate the effect of hydroxyurea (HU)
treatment on haematopoietic progenitors and CD34 positive (CD34+) cells in
patients with polycythaemia vera (PV) and essential thrombocythaemia (ET). Of
the PV patients were 10 treated with phlebotomy only and 10 were on HU therapy.
Seven ET patients were untreated and 10 received HU. In each subject peripheral
blood was obtained for in vitro colony growth, determination of CD34+ cells and
plasma erythropoietin (EPO) concentration. The mean number of EPO independent
erythroid colonies (EEC) was higher in the group of PV patients on phlebotomy
therapy compared to the PV patients treated with HU (74.4 and 8.0 colonies/10(5)
cells, respectively) but the difference did not reach statistical significance.
The corresponding means for the untreated ET patients and ET patients treated
with HU were 13.0 and 1.3 colonies/10(5) cells, respectively, this difference
being statistically significant (p = 0.012). The mean EEC for combined groups of
PV and ET without myelosuppressive treatment were compared with the results for
PV and ET patients on HU therapy; this difference was statistically significant
(p = 0.014). The same pattern was observed for total erythroid growth with EPO.
The relationship between the concentration of CD34+ cells and total EEC in
peripheral blood was statistically significant for both PV (p<0.005) and ET
(p<0.01). This finding supports the hypothesis that the level of CD34+ cells in
peripheral blood could be used as a proliferation marker in these two
myeloproliferative entities. No relationship between plasma EPO and EEC was
present. It therefore appears that the reported differences in plasma/serum EPO
concentrations between PV patients on phlebotomy treatment compared to patients
on myelosuppressive treatment are not likely to be found at the production site
for erythrocytes.
PMID: 10997885 [PubMed - indexed for MEDLINE]
19: European Journal of Haematology. 2000 Jan;64(1):32-41.
Polycythaemia vera: bone marrow histopathology under treatment with interferon,
hydroxyurea and busulphan.
Kreft A, Nolde C, Busche G, Buhr T, Kreipe H, Georgii A.
Little is known about long-term effects of myelosuppressive therapy on bone
marrow of patients with polycythaemia vera, since histopathology from follow-up
biopsies has not been frequently reported. Thus we conducted a retrospective
morphometrical analysis of diagnostic and follow-up biopsies of 62 patients,
evaluating fibre content, megakaryocytes and bone marrow cellularity. 8/62
patients were treated with interferon-alpha (INF), 11/62 with hydroxyurea (HU)
and 11/62 with busulphan (BU). 32/62 served as controls; they were not treated
with myelosuppressive drugs but with phlebotomy only. The median observation
time was 2.3 yr. Results were compared on the basis of change per time. The bone
marrow of the patients with phlebotomies only was characterised by increasing
cellularity of haematopoesis, number and volume ratio of megakaryocytes and
fibre content. In BU- and HU-treated patients, the haematopoesis was
significantly reduced. The IFN patients revealed a reduction of cellularity
which was not significant. The fibre content was reduced by BU only, but not
significantly. No correlation between megakaryocytes and fibres was found. It
could be concluded therefore that: 1) fibre proliferation within the bone marrow
was not significantly altered by IFN, HU or BU. 2) Cellularity of haematopoesis
was reduced significantly by HU and BU but only partly by IFN, corresponding
with haematological remission.
PMID: 10680703 [PubMed - indexed for MEDLINE]
Please let me know if I can clarify anything in this answer (or if
there's an aspect I've missed) before leaving feedback. Thanks!
Librariankt |
