Jennie Treleaven

Guidelines on the use of irradiated blood components prepared by the British Committee for Standards in Haematology blood transfusion task force

Search terms included: Transfusion-associated graft-versus-host disease, Transfusion-associated graft-versus-host, TA-GvHD. The last guideline covering this topic was published in 1996 (British Committee for Standards in Haematology (BCSH) Blood Transfusion Task Force, 1996. The writing group produced the new draft guideline, which was subsequently revised by consensus by members of the Haemato-oncology and Blood Transfusion Task Forces of the BCSH. The guideline was then reviewed by a sounding board of approximately 100 UK haematologists, the BCSH and the committee of the British Society for Haematology and amended, again by consensus. Criteria used to quote levels and grades of evidence are according to the GRADE system (Guyatt et al, 2006). Strong recommendations (grade 1, ‘recommended’) are made when there is confidence that the benefits either do or do not outweigh the harm and burden and costs of treatment. Where the magnitude of benefit or not is less certain a weaker grade 2 recommendation (‘suggested’) is made. Grade 1 recommendations can be applied uniformly to most patients whereas grade 2 recommendations require judicious application. The quality of evidence is graded as A (high quality randomized clinical trials), moderate (B) or low (C). This publication reports the key recommendations of the Writing Group. It is also accessible at http://www.bcshguide lines.com.

Additional chromosome abnormalities confer worse prognosis in acute promyelocytic leukaemia

Acute promyelocytic leukaemia (APL) has been associated with a favourable prognosis in many studies of acute myeloid leukaemia. A series of 54 patients treated at the Royal Marsden Hospital between 1979 and 1996, with APL and the t(15;17) chromosome translocation at pres‐entation, was examined for the effect of additional chromosome abnormalities in their presentation karyotype on survival.

Pilocarpine Hydrochloride for Symptomatic Relief of Xerostomia Due to Chronic Graft-Versus-Host Disease or Total-Body Irradiation After Bone-Marrow Transplantation for Hematologic Malignancies

Xerostomia due to chronic graft-versus-host disease (GVHD) or total-body irradiation (TBI) is an important cause of morbidity after BMT. The ophthalmic or oral form of pilocarpine, a parasympathomimetic agent with predominantly muscarinic activity, was given orally to 13 patients with moderate (n = 6) or severe (n = 7) xerostomia due to chronic GVHD (n = 7) or TBI (n = 6). The duration of 19 courses of therapy was 7-245 days (median 73). Ten patients (77%) noticed significant improvement in salivation and relief of symptoms which reached its maximum after 7-186 days (median 46). Difficulty in eating and speaking reduced, and there was a beneficial effect on the oral mucosa and teeth. Xerophthalmia improved in one of six patients. Five patients had adverse reactions: wheezing (n = 1), and increased sweating without (n = 3) or with (n = 1) abdominal cramps (n = 1): leading to discontinuation of pilocarpine in one. Three patients stopped pilocarpine, became symptomatic again, but the benefits were reproducible on restarting pilocarpine. The ophthalmic preparation was as effective as the oral, and was one-tenth the cost of the oral. We conclude that oral pilocarpine is effective in relieving xerostomia associated with chronic GVHD and TBI. The time taken for a response to be seen is variable, and unless significant adverse effects are encountered, pilocarpine should be continued for 6-8 weeks before it is considered to have failed.

Arsenic and Ayurveda

Manufacture of an Ayurvedic arsenic-containing compound is described, which is currently in use in India to control blood counts of patients with haematological malignancies. The efficacy and side effects of this compound are evaluated in the light of the fact that arsenic was recognised to be of use in the control of blood counts from patients with chronic myeloid leukaemia as long as 100 years ago, in the West.

Autologous Transplantation with CD52 Monoclonal Antibody-Purged Marrow for Acute Lymphoblastic Leukemia: Long-Term Follow-Up

During 1984-86, 23 patients (5-37 years, median 16) with acute lymphoblastic leukemia (ALL) in first remission (n = 11) or beyond (n = 12) underwent autologous transplantation (ABMT) using marrow purged with the rat anti-CD52 monoclonal antibody Campath-1M after melphalan and total-body irradiation (TBI). Median time to 0.5 x 10(9)/L neutrophils and 50 x 10(9)/L platelets was 38 and 51 days respectively. Myeloid engraftment was significantly slower compared with ALL patients receiving unpurged marrow (P = .01). Eight patients died due to transplant-related causes 53-205 days after the procedure. Six of eight patients receiving 1150 cGy TBI died of toxicity compared with two of 15 receiving less than 1150 cGy (P = .006, Fishers exact test). Nine patients relapsed at 45-195 days (median 97); eight died and one is alive at nine years in a chemotherapy-induced remission. Six patients are alive and well in continuous remission 9-10 years (median 10) after transplant. The 10-year probabilities of disease-free survival and relapse are 26% (95% CI: 11-45%) and 51% (95% CI: 37-59%) respectively. We conclude that it is feasible to purge marrow for autografting using Campath-1M without killing normal stem cells. Myeloid engraftment is slow but consistent, and long-term survival is seen in a proportion of patients. The role of CD52 monoclonal antibodies for purging in ALL still requires further study.

An Unusual Presentation of Acute Mveloid Leukaernia with Pericardial and Pleural Effusions Due to Granulocytic Sarcoma

We describe a case of acute myeloid leukaemia (Mo) presenting with pericardial and pleural effusions due to a granulocytic sarcoma adherent to the thymus gland situated in the anterior mediastinum. This has not been described previously in the setting of AML Mo.

Long-Term Safety of GM-CSF (Molgramostim) Administration After Allogeneic Bone Marrow Transplantation for Hematologic Malignancies: Five-Year Follow-Up of a Double-Blind Randomized Placebo- Controlled Study

In a double-blind, randomized study performed between 1988 and 1990, 40 patients undergoing allogeneic BMT from HLA-identical siblings for hematologic malignancies received 8 mg/kg/d rHuGM-CSF (molgramostim, n = 20) for 14 days. The median neutrophil count on day 14 was significantly higher in the GM-CSF group (1.90 vs 0.46 yen 10(9)/L, P < .0001). The incidence of acute GVHD and transplant-related mortality were comparable. Only two deaths occurred after 6 months; one due to pulmonary fibrosis in the GM-CSF group on day 1591, and one due to relapse on day 1590 in the placebo group. The Karnofsky score of the 10 survivors, 3 in the placebo group and 7 in the GM-CSF group, is 90-100% (median 100%), and none has chronic GVHD requiring therapy. There was no evidence of increased relapse in the GM-CSF group with only two relapses occurring; both in the placebo group. With a follow-up of 4.5-6.8 years (median 5.5 years), these patients are amongst the longest surviving patients to have received a recombinant growth factor post-allograft. We conclude that the administration of GM-CSF after allogeneic BMT does not appear to be associated with an increased incidence of chronic GVHD or relapse, or of other adverse effects such as the development of myelodysplasia.

Prospective, concurrent comparison of the Cobe Spectra and Haemonetics MCS-3P cell separators for leukapheresis after high-dose filgrastim in patients with hematologic malignancies

A prospective study was undertaken to compare the mononuclear cell, CD34+ cell, and CFU‐GM yields of the Haemonetics MCS‐3P and the Cobe Spectra cell separators in ten patients (nine multiple myeloma and one non‐Hodgkin lymphoma) on two consecutive days after mobilization with high‐dose filgrastim (12–16 μg/k) for 4 days. All patients were harvested once on each machine, five starting on each machine. The target duration of the procedure on the Spectra was 160 minutes, and the target blood volume processed on the MCS‐3P was 60–70 ml/kg body weight. Both machines were operating on the 1995 software versions supplied by the respective manufacturers. The time taken for the procedure was significantly longer with the Haemonetics machine. The volumes of blood processed and the product collected were significantly higher with the Spectra, as were the absolute mononuclear and CD34+ cell yields, and yields per unit time. Mononuclear and CD34+ cell yields per unit volume of blood processed were comparable for both machines. The differences in CFU‐GM yields were not significant, largely because of wide interpatient variations. The extent of platelet depletion as a result of the procedure was greater with the Spectra because of the higher blood volume being processed. We conclude that the Cobe Spectra is a significantly faster machine than the Haemonetics MCS‐3P; and consequently, its use is associated with higher mononuclear and CD34+ cell yields. J. Clin. Apheresis 12:63–67, 1997.

Oral Idarubicin as a Single Agent Therapy in Patients with Relapsed or Resistant Multiple Myeloma

The established treatment for multiple myeloma (MM) comprises induction with infusional chemotherapy, high dose chemotherapy (HDC) and autologous transplantation followed by maintenance interferon. On relapse, patients (pts) are reconsidered for this however some are unsuitable and in this situation the therapeutic options are limited. Between June 1995 and May 1997, 14 pts with previously treated relapsed or refractory MM were recruited. Using a prospective database, the tolerability and efficacy of chronic low dose oral idarubicin was evaluated. The median age of pts was 63 years. All had received previous anthracycline in the form of infusional cVAMP chemotherapy. 11/14 had received previous HDC. Median time from diagnosis to commencing idarubicin was 77 months. 10 mg idarubicin was administered 3 times/week for 3 weeks of a 5 week cycle. The maximum number of courses was 6. Three pts completed 6 courses, 5 pts 3 courses, 2 pts 2 courses and 4 pts 1 course. The reasons for stopping treatment were death due to progressive disease (PD) in 7 pts, persistent thrombocytopenia in 2 pts, PD in 1 pt and 1 pt suffered a cerebral infarction not considered to be related to the idarubicin therapy. Two pts showed evidence of response, neither amounting to a partial response. One had stabilisation of paraprotein with a reduction in bone marrow infiltration (47% to 7% plasma cells), the other had a reduction in bone marrow infiltration after 3 course but an increase after 6 courses. In total forty-one courses of treatment were administered. Grade 3/4 haematological toxicities were noted in a minor fraction of cases and were as follows: anaemia 6/41, neutropenia 10/41 and thrombocytopenia 11/41. Our data therefore shows a minor response in 2/14 (14%) of heavily pretreated patients with MM, without evidence of severe toxicity. It provides the rationale for using oral idarubicin as either single agent or in combination therapy for patients earlier on in their disease course especially if they are unsuitable for standard therapy.

Idarubicin, High-dose Cytarabine and Etoposide for Remission Induction in Therapy-Related Acute Myeloid Leukemia

Five patients with therapy-related acute myeloid leukemia received combination induction chemotherapy with idarubicin, high-dose cytarabine, and etoposide. Complete remission was achieved in all patients with a single course of therapy. Treatment-related toxicity included nausea, vomiting, mucositis, diarrhea, and liver and kidney function abnormalities, and was low in all patients. There were no deaths during induction therapy. We conclude that this combination is well-tolerated in induction of remission in secondary acute myeloid leukemia, and warrants further assessment because of a very good complete remission rate.