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Since 2005, University College London Hospital (UCLH) has operated a hotel-based Ambulatory Care Unit (ACU) for hematology and oncology patients requiring intensive chemotherapy regimens and hematopoietic stem cell transplants. Between January 2005 and 2011 there were 1443 patient episodes, totaling 9126 patient days, with increasing use over the 6-year period. These were predominantly for hematological malignancy (82%) and sarcoma (17%). Median length of stay was 5 days (range 1-42), varying according to treatment. Clinical review and treatment was provided in the ACU, with patients staying in a local hotel at the hospital's expense. Admission to the inpatient ward was arranged as required, and there was close liaison with the inpatient team to preempt emergency admissions. Of the 523 unscheduled admissions, 87% occurred during working hours. An ACU/hotel-based treatment model can be safely used for a wide variety of cancers and treatments, expanding hospital treatment capacity, and freeing up inpatient beds for those patients requiring them.

Treatment options for patients who relapse following autologous transplantation for Hodgkin's lymphoma are limited. There are anecdotal reports of lengthy remissions following second autologous procedures, although treatment-related toxicity can be significant. We report a single centre experience of second autologous transplant performed in seven highly selected patients, who relapsed following initial high-dose therapy. They were all young and had slow tempo disease, which was still sensitive to conventional dose chemotherapy. All received BEAM conditioning for the first transplant, and six of the seven received BEAM for the second. All six of these patients regenerated successfully and with no delay, the final patient dying during the procedure following alternative conditioning. Only one case of presumed carmustine-related pneumonitis was seen, which responded rapidly to corticosteroid therapy. Four patients have subsequently relapsed, of whom three have died at 29, 33, and 38 months postprocedure. One is alive with active disease at 68 months, and the final two are alive and in continuing complete remission at 104 and 68 months.

Allogeneic hematopoietic stem cell transplantation (HSCT) has been restricted to medically fit patients under the age of 55 years due to adverse effects of the intensive conditioning regimens. Autologous HSCT has not proven to be a particularly effective treatment for patients with low-grade non-Hodgkin's lymphoma (NHL). Much of the benefit of allogeneic HSCT appears to be mediated by a graft-vs.-tumor (GVT) effect. Reduced-intensity regimens in allogeneic HSCT have been developed to minimize conditioning regimen-related toxicities and to control the malignancy until a GVT effect is established. A number of studies investigating reduced-intensity allogeneic HSCT are discussed. Results from these studies suggest that indications for allogeneic transplant include patients with low-grade NHL with a sibling or matched donor who are under 60 years of age; young patients with mantle cell lymphoma who are in first remission and have a sibling or matched donor; patients with high-grade NHL who have already failed an autograft but have chemosensitive disease, and those under 30 years of age who have poor-risk disease and are in first remission. It is concluded that reduction in treatment-related mortality with reduced-intensity HSCT and the presence of GVT effects increases the applicability of allogeneic transplantation for NHL. However, treatment will be improved by optimizating conditioning regimens and a better understanding of patient selection criteria and the immune processes involved in graft-vs.-host disease and GVT.

Forty patients, with mainly poor risk haematological malignancies, were given the new regimen FLAG, comprising fludarabine, arabinosyl cytosine and G-CSF. Twenty four patients had acute myeloid leukaemia (AML), 8 patients myelodysplastic syndrome (MDS) and a further 8 patients had a variety of other haematological malignancies. The response rates for 19 relapsed and 4 refractory AML patients were 68% and 100% respectively and comparable to those attained using other regimens, although the numbers are small. Of 8 patients with MDS, 7 showed some response with 4 remaining in an improved disease status 5-12 months after FLAG. Follow-up has been too short thus far to provide any survival data in both patient groups. In general, the other smaller group of 8 patients (3 transformed chronic myeloid leukaemia (CML), 3 acute lymphoblastic leukaemia (ALL), 2 granulocytic sarcoma (GS) did poorly with response shown in 1 only. The regimen was well tolerated with 4 procedure-related neutropenic deaths. The neutropenic and thrombocytopenic periods are generally short when compared with those from current protocols. The overall modest toxicity may encourage combination with other anti-leukaemic agents and be of particular use in the aged or heavily pre-treated patients. Preliminary results may favour the setting up of controlled trials to properly evaluate the benefit of FLAG.

The control of cell growth and differentiation in B-cell malignancies may be regulated by the autocrine production of cytokines, several of which have been implicated in the growth and survival of B-cells. The effect of interferon-alpha (IFN) therapy in these disorders may be to disrupt autocrine growth or survival loops. We have measured levels of circulating IL-1b, IL-6, TNF-a and soluble CD23 (sCD23) in 8 patients with Binet stage A B-cell chronic lymphocytic leukaemia (B-CLL) receiving IFN therapy, and compared these with changes in the lymphocyte count following IFN therapy. Two patients developed anti-interferon antibodies while on IFN therapy, and in both them, the changes in lymphocyte count correlated significantly with the titre of anti-interferon antibodies, as well as serum levels of IL-6, TNF-a and sCD23. In one patient there was significant correlation with levels of IL-1b. One patient, who stopped and restarted IFN therapy, demonstrated correlation between lymphocyte count and levels of IL-6 and sCD23. In a further two patients, there was correlation with levels of sCD23 alone, while the remaining three patients showed no correlation between lymphocyte count and the serum cytokines measured. These results suggest that IFN therapy may alter levels of circulating cytokines in some CLL patients and that these effects may be associated with disease progression.

The proliferation and survival of B-chronic lymphocytic leukaemia (B-CLL) cells may be regulated by autocrine growth factor loops. Furthermore, it has been suggested the reduction in lymphocytosis following therapy with interferon-alpha may be associated with the interruption of autocrine growth factor production. We have therefore examined the effects of a number of cytokines on the proliferation of B-CLL cells, and also on the regulation of programmed cell death, and the role of interferon-alpha in these systems. In the ten patients studied, neither interferon-alpha alone or together with either interferon-gamma, IL1, IL4, IL6, TNF, or serum containing high levels of soluble CD23 was able to induce proliferation of B-CLL cells. Incubation with TPA or IL2 resulted in variable proliferative responses. Co-incubation with interferon-alpha enhanced TPA-induced proliferation in 4 cases, but reduced IL2-induced proliferation in all cases studied. In contrast, all the cytokines studied were able to protect B-CLL cells against programmed cell death, both spontaneous and that induced by hydrocortisone, with the exception of TNF. These data suggest a role for interferon-alpha in disrupting autocrine survival pathways rather than inhibiting proliferation.

Autologous bone marrow- and blood progenitor cell transplantation was performed in 130 patients with multiple myeloma in 16 European centers between 1986 and 1993. At the time of follow-up, 77 patients were alive and 53 were dead. Complete remission after transplantation was obtained in 47% of all patients. The actuarial survival at 65 months was 28%. The median duration of relapse-free survival among patients who were in complete remission after transplantation was 29 months. The following factors were predictive for longer survival and freedom of progression in a univariate analysis: Male sex, age less than 45 years, a low serum-beta-2-microglobulin value at diagnosis, prior administration of only one treatment regimen, response on conventional chemotherapy immediately pretransplant and the use of a preparative regimen including melphalan. The last factor, in addition to stage I disease at diagnosis, male sex and responsive disease immediately pretransplant, were also demonstrated as independent predictive variables for longer survival in a multivariate analysis. Progression-free survival was significantly better for patients who were in complete remission after transplantation, as compared to those with persisting signs of disease. We conclude that high-dose chemo-radiotherapy with autologous stem cell transplantation can induce long-term responses, primarily in younger, male patients with chemotherapy-responsive early disease. High-dose melphalan, as single drug or in combination, appeared to be superior to other regimens. The chance of being persistently disease-free seemed to be greatest for patients being in complete remission already before the transplantation.

We report the complications and outcome of high-dose melphalan and TBI combined with ABMT used in the treatment of multiple myeloma at a single centre. Twenty-three patients, aged 65 years or less, who underwent the procedure are reviewed. All had chemosensitive disease. Response to ABMT assessed at 3 months showed 75% of evaluable patients to have further tumour cytoreduction of at least 50%, with 24% of patients who entered ABMT with residual disease eventually achieving CR. There was one toxic death. The overall survival is 60% and the progression-free survival is 49.8% at a median follow-up time of 17 months. Relapse or disease progression has occurred in 27% of patients, of whom half have died. No significant prognostic factors affecting survival were found although those patients with IgG myeloma had a better outcome. Patients transplanted in first plateau appeared to do significantly better if they had been resistant to their first-line chemotherapy but had then responded to further conventional chemotherapy (p = 0.029).

We describe a case of a 47 year old man with CLL who was treated with 7 courses of fludarabine with simultaneous suppression of his pituitary-testicular axis (P-T) with Gonadotrophin releasing hormone (GnRH) and replacement treatment with testosterone. Despite initial gonadal damage as evident by endocrine and sperm studies, testicular recovery was observed 11 months post treatment. Although spontaneous recovery cannot be ruled out, continuous treatment with GnRH and testosterone may play a crucial role protecting the gonads from the cytotoxic effects of the chemotherapeutic agents.

The pattern of haemopoietic reconstitution after autologous bone marrow transplantation has been studied on 73 adult lymphoma patients (pts) using a flow cytochemistry blood autoanalyser (Technicon H*1). Thirty-six pts received haemopoietic growth factors (17 had M-CSF, 9 GM-CSF and 10 G-CSF). The first neutrophils appeared concurrently in all groups and most of the pts reached a neutrophil count of 0.1 × 109/1 by day +13; recovery was then accelerated significantly in the GM-CSF pts. Neutrophil recovery to 0.5 × 109/1 took 19.4 days for pts who received growth factors vs 24.7 days for the controls, with the GM-CSF group recovering earliest (mean day +14.1). The GM-CSF pts developed transient eosinophilia during the 3rd week post transplant. Monocyte recovery as well as the onset of blast flag, H (high) monocyte percentage flag and H (high) LUC (Large Unstained Cells) percentage flag preceded significantly the neutrophil recovery.

Recent studies have shown that, when used in early stage disease, interferon-alpha (IFN-alpha) can produce a fall in the number of malignant cells in the peripheral blood of patients with B-CLL. In this study, we investigated the effect of IFN-alpha on natural killer (NK) cell and lymphokine-activated cell (LAK) activity in patients with B-CLL. In vitro, IFN-alpha (500 U/ml for 18 hours) induced LAK activity in patients with B-CLL (27.7 +/- 9.9%, n = 20), and IL-2 (500 U/ml for 5 days) produced similar activity (35.9 +/- 8.8%, n = 7). Despite the induction of LAK activity by IFN-alpha and IL2 in patients with B-CLL, the malignant cells remained resistant to both allogeneic and autologous LAK effectors. NK activity in patients with B-CLL is also low (23.1 +/- 7.2%, n = 20), and B-CLL cells were resistant to NK cell activity. In cold target competition assays, CLL cells did not compete with labelled K562 or Daudi targets in the NK and LAK assays, suggesting that the malignant cells are not recognised by the effector cells, and this may be related to low level of expression of the adhesion receptors, LFA-1 and ICAM-1. Finally, CLL cells were also resistant to antibody dependent cell mediated cytotoxicity, but were susceptible to antibody dependent complement mediated lysis. These results suggest that it is unlikely that the effects of IFN-alpha in B-CLL are due to the enhancement of NK or LAK activity.

The outcome of conventional therapy in adult acute lymphoblastic leukaemia (ALL) is disappointing. Allogeneic bone-marrow transplantation may give improved results but has only limited applicability because of the lack of a suitable donor in most patients. We have therefore investigated intensive chemotherapy and chemo/radiotherapy protocols with autologous bone-marrow rescue. 31 patients have been treated, 14 beyond first remission and 17 in first remission. The result of this therapy in both groups is poor with only 2 longterm survivors in each group. There is no reason to believe from this study that ablative therapy with autologous bone-marrow rescue will yield superior results to conventional therapy in adult ALL but further experience with TBI containing regimes is required.

The pattern of disease relapse in nine patients with multiple myeloma who had received double hemi body irradiation therapy is analysed. This analysis highlights the localisation of these relapses to skeletal areas excluded from initial radiation fields. This phenomenon was also documented in a patient who received systemic irradiation as part of a conditioning regimen per allogeneic bone marrow transplantation.

Recombinant alpha 2a, 2b and 2c interferons have been shown to be effective short-term agents in essential thrombocythaemia and thrombocythaemia associated with the other myeloproliferative disorders, including chronic granulocytic leukaemia, polycythaemia rubra vera and myelofibrosis. Few data exist on the use of the recombinant interferons as maintenance agents in patients with thrombocythaemia. We report on a cohort of 22 previously untreated patients, with essential thrombocythaemia, treated with recombinant alpha 2a interferon maintenance therapy for a minimum period of 6 months. Effective long-term control of platelet counts, without evidence of haematological toxicity, was achieved in 19 of 22 patients. No objective haemorrhagic or thrombotic event occurred in 298 patient months of interferon therapy. Three patients discontinued alpha interferon therapy due to adverse side-effects. Alpha 2a interferon is an effective maintenance agent in essential thrombocythaemia.

With optimum treatment, approximately 75% of patients with Hodgkin's disease (HD) can expect to be cured.' Even for patients with advanced disease, the advent of combination chemotherapy has meant that around 75% are alive at 5 years.2 Autologous bone marrow transplantation (ABMT) is now accepted as appropriate treatment for those patients who fail to attain a complete remission (CR) on a standard combination regimen, those whose first CR lasts less than a year, those who fail to achieve a second CR or who have a further relapse, and those with refractory disease.3" The use of ABMT in first CR re

We report here a patient with acute mycloid leukaemia who relapsed 20 months after undergoing a double autograft procedure in first remission. He was reinduced and subsequently underwent a third autologous bone marrow transplantation in second remission using bone marrow harvested in second remission and a Busulphan and Cyclophosphamide conditioning regimen. Although the engraftment was very slow, he has remained in second remission for 34+ months. This case demonstrates that durable disease-free survival can be attained by a second preparative therapy, even in second remission, for patients relapsed after autologous bone marrow transplantation.

Dear Sir, Secondary neoplasms following immunosuppression are a well-described entity. Here, we report a case of a 28-year-old Arabian woman with de novo AML who developed a squamous cell carcinoma (SCC) of the axilla while she was receiving the third course of induction chemotherapy. She was diagnosed as having acute myeloid leukemia (AML) M5 with normal cytogenetics and was treated with two courses of DAT chemotherapy (daunorubicin, cytarabine, 6-thioguanine) attaining only partial remission (10% marrow blasts following the first course and 7% following the second). She was subsequently salvaged with one course of FLAG-lda chemotherapy (fludarabine, cytarabine, G-SCF, idarubicin), achieving complete remission (blasts less than 5% in the marrow). This was followed by a second similar course but during the period of aplasia, she developed a rapidly growing inflammatory lesion in the left axilla, which was thought to be of infectious origin. Surgical drainage and biopsy revealed SCC. Further clinical and imaging investigations confirmed localised non-metastatic disease. HIV serology was negative. The patient was treated successfully with local radiotherapy at a dose of 44 Gy and the anti-leukaemic treatment was completed with a final course of chemotherapy which consisted of mitoxantrone and cytarabine (MidAC).