Improved survival in red blood cell transfusion dependent patients with primary myelofibrosis (PMF) receiving iron chelation therapy.

Many patients with primary myelofibrosis (PMF) become red blood cell (RBC) transfusion dependent (TD), risking iron overload (IOL). Iron chelation therapy (ICT) may decrease the risk of haemosiderosis associated organ dysfunction, though its benefit in PMF is undefined. To assess the effect of TD and ICT on survival in PMF, we retrospectively reviewed 41 patients. Clinical data were collected from the database and by chart review. The median age at PMF diagnosis was 64 (range 43-86) years. Median white blood cell (WBC) count at diagnosis was 7.6 (range 1.2-70.9) x 10(9)/L; haemoglobin 104 (62-145) G/L; platelets 300 (38-2088) x 10(9)/L. Lille, Strasser, Mayo and International Prognostic System (IPS) scores were: low risk, n = 15, 8, 11, 3; intermediate, n = 15, 19, 9, 16; high, n = 5, 11, 5, 7; respectively. Primary PMF treatment was: supportive care, n = 23; hydroxyurea, n = 10; immunomodulatory, n = 4; splenectomy, n = 2. Sixteen patients were RBC transfusion independent (TI) and 25 TD; of these 10 received ICT for a median of 18.3 (0.1-117) months. Pre-ICT ferritin levels were a median of 2318 (range 263-8400) and at follow up 1571 (1005-3211 microg/L (p = 0.01). In an analysis of TD patients, factors significant for overall survival (OS) were: WBC count at diagnosis (p = 0.002); monocyte count (p = 0.0001); Mayo score (p = 0.05); IPS (p = 0.02); number of RBC units (NRBCU) transfused (p = 0.02) and ICT (p = 0.003). In a multivariate analysis, significant factors were: NRBCU (p = 0.001) and ICT (p = 0.0001). Five year OS for TI, TD-ICT and TD-NO ICT were: 100, 89 and 34%, respectively (p = 0.003). The hazard ratio (HR) for receiving >20 RBCU was 7.6 (95% Confidence Intervals [CI] 1.2-49.3) and for ICT was 0.15 (0.03-0.77). In conclusion, 61% of PMF patients developed RBC-TD which portended inferior OS; however patients receiving ICT had comparatively improved OS, suggesting a clinical benefit. Prospective studies of IOL and the impact of ICT in PMF are warranted.

Clinical progression and outcome of patients with monoclonal B-cell lymphocytosis.

Monoclonal B-cell lymphocytosis (MBL) is a clonal lymphoproliferation with the immunophenotype of chronic lymphocytic leukemia (CLL) but a B-lymphocyte count of less than 5 x 10(9)/l and no lymphadenopathy, organomegaly, cytopenias or symptoms. We performed a retrospective analysis of patients with MBL (n = 46), Rai stage 0 CLL (n = 112) and Rai stage > or =1 CLL (n = 54). Median follow-up and range was 30 (0.1-120) months for MBL, 60 (0.1-309) months for stage 0 CLL and 54 (0.1-309) months for stage > or =1 CLL. None of the MBL patients required treatment compared with 24 of 112 (21%) stage 0 CLL and 28 of 54 (52%) stage > or =1 CLL patients (p < 0.0003). No MBL underwent aggressive transformation compared with 1 of 112 (0.8%) stage 0 CLL and 6 of 54 (11%) stage > or =1 CLL patients (p < 0.0003). Progression-free survival (PFS) appeared improved in MBL compared to stage 0 CLL, although this did not reach statistical significant (p = 0.07) due to the relatively short follow-up in the MBL group; two year PFS was 97.2% for MBL, 93.1% for stage 0 CLL, and 68% for stage > or =1 CLL patients (p < 0.0001 for stage > or =1 CLL compared with MBL and stage 0 CLL). This is the first study of outcome in MBL which demonstrates that patients have an improved disease course compared to stage 0 CLL patients. Over a median 2.5 years of follow-up, no MBL patients required treatment or died of CLL-related causes.

Durable Red Blood Cell Transfusion Independence in a Patient with an MDS/MPN Overlap Syndrome Following Discontinuation of Iron Chelation Therapy.

Background. Hematologic improvement (HI) occurs in some patients with acquired anemias and transfusional iron overload receiving iron chelation therapy (ICT) but there is little information on transfusion status after stopping chelation. Case Report. A patient with low IPSS risk RARS-T evolved to myelofibrosis developed a regular red blood cell (RBC) transfusion requirement. There was no response to a six-month course of study medication or to erythropoietin for three months. At 27 months of transfusion dependence, she started deferasirox and within 6 weeks became RBC transfusion independent, with the hemoglobin normalizing by 10 weeks of chelation. After 12 months of chelation, deferasirox was stopped; she remains RBC transfusion independent with a normal hemoglobin 17 months later. We report the patient's course in detail and review the literature on HI with chelation. Discussion. There are reports of transfusion independence with ICT, but that transfusion independence may be sustained long term after stopping chelation deserves emphasis. This observation suggests that reduction of iron overload may have a lasting favorable effect on bone marrow failure in at least some patients with acquired anemias.

Human immunodeficiency virus-associated multicentric Castleman disease refractory to antiretroviral therapy: clinical features, treatment and outcome.

Human immunodeficiency virus (HIV)-associated multicentric Castleman disease (MCD) is a lymphoproliferation associated with human herpes virus-8 (HHV-8). Optimal treatment in patients not responding to antiretroviral therapy (ART) is undefined. We report 12 patients with ART refractory HIV-MCD. Patients with HIV-MCD were identified and baseline characteristics, treatment and outcome considered. Median CD4 count at HIV-MCD diagnosis was 295 (60-950) cells/mL. All patients had waxing and waning systemic symptoms, lymphadenopathy and/or splenomegaly, with non-Hodgkin lymphoma (NHL) in three. Treatment included: anti-HHV-8 therapy, n = 8; alone, n = 4; with systemic chemotherapy (CT) ± immunotherapy (IT), n = 4; CT ± IT only, n = 2. Initial median HHV-8 viral load (VL) was 7 × 10(4) copies/mL and at follow-up < 40 in 6/7 survivors; and 403-7.2 × 10(6) in 4/5 who died. One patient developed NHL despite an HHV-8 VL < 40. HIV-MCD is challenging to treat. Suppression of plasma HHV-8 VL did not prevent development of NHL. Anti-HHV-8 therapy should probably be considered adjunctive to cytotoxic therapies.

Improved survival with iron chelation therapy for red blood cell transfusion dependent lower IPSS risk MDS may be more significant in patients with a non-RARS diagnosis.

Retrospective analyses suggest iron overload is associated with inferior survival (OS) in lower risk MDS and iron chelation therapy (ICT) with improvement. However, an analysis of RARS patients found no such association. We analyzed subtypes of lower risk MDS. Median OS for non-RARS without and with ICT was 44 months and not reached (P<0.001), and for RARS 99 and 134.4 months (P=NS); in red blood cell (RBC) transfusion dependent RARS patients not receiving ICT, median OS was 73.8 months (P=0.025). These results suggest a stronger association between ICT and OS in non-RARS MDS than in RARS, with significantly superior OS in transfusion dependent patients receiving ICT.

Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era.

The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 10(9)/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 10(9)/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed.

Acute leukemia in patients sixty years of age and older: a twenty year single institution review.

OBJECTIVES: Acute leukemia, particularly acute myeloid leukemia, occurs more frequently in the elderly, a growing segment of the North American population. To evaluate our progress in the diagnosis, treatment and outcome of this condition, we reviewed our experience of all patients > or =60 years of age diagnosed with acute leukemia over a 20-year period at Saint Paul's Hospital, a university-based hospital in Vancouver, Canada. METHODS: A retrospective chart review was performed of 103 patients > or =60 years of age diagnosed with acute leukemia (acute myeloid leukemia-81; acute lymphoid leukemia-15; acute leukemia not otherwise specified-7). RESULTS: Median age was 72 (range 60-88) years. Bone marrow aspirate yielded cytogenetic information on 57 patients and 18 (31.6%) had an unfavourable karyotype. Fifty-three (51%) patients received induction chemotherapy (treated) and 50 (49%) were palliated (untreated). Treated patients were younger [median 67 years (range 60-79)] than untreated patients [76 years (61-88)], (P < 0.0001). Of the treated patients, 33 (62%) achieved a complete remission. The median overall survival for the group was 104 (1-2689) days, and for treated versus untreated patients-219 (1-2689) and 39 (2-1229) days, respectively (P = 0.0021). Univariate variables predictive of prolonged survival included induction chemotherapy (P = 0.0027), de novo leukemia (P = 0.0420), and younger age, with a relative increase in death in older subgroups (60-69, 70-79, 80+), (P = 0.0311). Induction chemotherapy was the only predictor of prolonged survival in multivariate analysis (P = 0.0027). CONCLUSIONS: The prognosis of acute leukemia in older patients remains poor, and even though induction chemotherapy seem to prolong survival in patients able to receive treatment, most ultimately die of leukemia.

Hematopoietic stem cell transplantation: a primer for the primary care physician.

Hematopoietic stem cell transplantation has been used for many years to treat various malignant and nonmalignant hematologic conditions. However, the high-dose conditioning regimen can lead to major organ dysfunction, life-threatening infection and bleeding. In the allogeneic setting, graft-versus-host disease may also develop, making post-transplant management complex. Once a transplant recipient is discharged from hospital and returns to his or her local community, the primary care physician can play an important role in care. Recipients of stem cell transplants may be severely immunocompromised for many months after transplantation, especially if they are still taking immunosuppressive drugs. Furthermore, endocrine and metabolic deficiencies can develop, and transplant survivors are at risk of a second malignant disease. This review is intended as a basic overview of allogeneic and autologous stem cell transplantation with a special focus on long-term follow-up issues relevant to primary care providers.