Neena Kapoor

Verruciform xanthoma in a bone marrow transplant recipient

The verruciform xanthoma is an uncommon benign condition of uncertain cause that affects either mucosa or, less commonly, skin. Most lesions are solitary, and most have been reported to involve the oral mucosa. In some instances, chronic damage to the lesional site has been identified. This report describes a verruciform xanthoma that developed on the lower vermillion zone of the lip of a young person who had undergone allogeneic bone marrow transplantation for acute lymphoblastic leukemia. To our knowledge, this is the first reported case of this lesion occurring in a bone marrow transplantation patient. We speculate that immunologically mediated damage to the patients epithelium in this area may be related to the pathogenesis of the lesion.

Radiation-free preparation for allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia.

PURPOSE The study was undertaken to investigate the effectiveness of allogeneic bone marrow transplantation from HLA-identical siblings after preparation with busulfan and cyclophosphamide in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS Thirty-nine patients aged 15 to 42 years underwent transplantation at three different centers from November 1984 through November 1990. All patients received 16 mg/kg busulfan and 120 mg/kg cyclophosphamide as preparative therapy. Cyclosporine plus methotrexate or cyclosporine plus corticosteroids with or without methotrexate were given for prevention of graft-versus-host disease (GVHD). RESULTS Twelve patients died of treatment-related complications, 12 patients relapsed, and 15 patients are leukemia-free survivors. For 27 patients in group 1 (first remission, second remission, first relapse), the estimated leukemia-free survival (LFS) rate is 42.3% (95% confidence interval [CI], 22.9% to 71.7%) at 3 years. For 12 patients with more advanced disease (group 2), the 1-year LFS rate is 13.5% (95% CI, 0% to 37.1%). Chronic GVHD occurred at an estimated incidence of 63.3% and developed significantly more frequently among patients who received corticosteroids for prevention of acute GVHD. Chronic GVHD was associated with a significantly lower incidence of relapse and with improved LFS rates. CONCLUSION LFS rate in this study is comparable to that obtained with radiation-containing regimens; however, the effectiveness of this preparative regimen in ALL requires further study.

Marrow transplantation following busulfan and cyclophosphamide for chronic myelogenous leukaemia in accelerated or blastic phase

Summary. Between July 1984 and October 1987, 21 patients with chronic myelogenous leukaemia in an accelerated or blastic phase were treated with 16 mg/kg of busulfan and 120 mg/kg of cyclophosphamide followed by infusion of bone marrow from an HLA‐identical sibling donor. The regimen was well tolerated. Except for one individual with severe marrow fibrosis all patients achieved a complete remission. Only one patient relapsed. Seven of 13 patients transplanted in an accelerated phase and five of eight transplanted in a blastic phase are alive without Philadelphia chromosomes between 8 and 48 months (median 29 months) following transplantation. The estimated probability of relapse‐free 3‐year survival is 55%. These results indicate that busulfan and cyclophosphamide combined with allogeneic marrow transplantation exert a potent anti‐leukaemic effect in patients in the accelerated or blastic phase of CML.

Cyclosporine-associated Seizures In Bone Marrow Transplant Recipients Given Busulfan And Cyclophosphamide Preparative Therapy

Five of 182 recipients of allogeneic bone marrow transplants performed between 2/84 and 6/90 developed seizures while receiving cyclosporine and methylprednisolone to prevent acute graft-versus-host disease. All received a radiation-free regimen of busulfan and cyclophosphamide as preparative therapy. Two patients received HLA-mismatched allografts; and three patients received marrow from HLA-identical sibling donors. Two patients had received extensive intrathecal therapy prior to transplantation. All patients were receiving standard prophylactic doses of CsA and MP at the time of onset (median 31 days posttransplantation) of seizures. Three patients had mild-to-moderate hypertension and varying degrees of morphologic evidence of microangiopathic hemolytic anemia. None had unusually low magnesium levels. Cyclosporine levels were not in the toxic range. Cranial magnetic resonance imaging and computed tomography (CT) showed bilateral abnormalities primarily in the posterior temporal, occipital, and parietal lobes. These abnormalities were shown to be transient on sequential MRI exams in two patients. Seizures as well as radiologic abnormalities resolved on stopping CsA and did not recur in 2 patients who subsequently received CsA in lower doses. These findings confirm and expand previous observations of CsA-associated seizures and demonstrate that they occur in allogeneic bone marrow transplant recipients following a radiation-free preparative regimen of busulfan and cyclophosphamide.

Bone marrow transplantation without total-body irradiation in patients aged 40 and older

We evaluated relapse-free survival and the incidence and type of complications in 17 patients aged 40 or older with chronic myelogenous leukemia, acute myelogenous leukemia, or lymphoma who underwent allogeneic marrow transplantation following busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. Nine patients are diseasefree survivors 5–38 months (median 26 months) following transplantation. The incidence of grades II-IV acute graft-versus-host disease was 35%. No significant difference was detected in the incidence of GVHD or interstitial pneumonia between patients aged 40 and older and a group of younger patients transplanted over the same time period. These observations should encourage consideration of allogeneic marrow transplantation in older patients and suggest that this busulfan-cyclophosphamide regimen is a promising alternative to regimens containing total-body irradiation in older individuals.

MARROW TRANSPLANTATION FOLLOWING BUSULFAN AND CYCLOPHOSPHAMIDE AS TREATMENT FOR TRANSLOCATION (4:11) ACUTE LEUKAEMIA

The lineage association between B-CLL and myeloma (both mature B cell malignancies) might suggest that complicating myeloma would arise by clonal evolution of pre-existing BCLL. analogous to the transformation seen in Richter’s syndrome. Our data indicates that, at least in some cases, such evolution would have to occur in a leukaemic stem cell at a stage before commitment to a B cell lineage differentiation programme defined by IgH gene rearrangement. An alternative, more likely explanation, assuming no large-scale hypermutation (see Cleary et al, 1988) is that these diseases have an independent clonal origin in B cell progenitor compartment(s). This raises the possibility that factors such as impairment of immune surveillance may be important in accounting for the increased frequency of secondary malignancies in B-CLL. kbP

High dose intravenous gammaglobulin as an approach to treatment of antibody mediated pancytopenia

mature appearing plasma cells being the end result (Gordon et al, 1984: Ostlund et al, 1986). It seems likely that spontaneous complete remission in CLL is achieved by an immuno-regulatory effect, possibly through endogenous interferon, whose production may be provoked by viral infection. This raises exciting therapeutic possibilities, but clinical trials with LY interferon preparations in advanced disease have so far proved disappointing (Huang et al, 1982: Foon et al, 1985). A more recent trial of recombinant LY Interferon in early untreated CLL has been more promising (Montserrat et d, 1986). Phase I1 trials with recombinant y Interferon in CLL are currently in progress.

Megakaryocyte colony stimulating activity in allogeneic bone marrow recipients prepared with busulfan and cyclophosphamide

Summary Increased megakaryocyte colony stimulating activity (MK‐CSA) has been reported after total body irradiation (TBI) for bone marrow transplant (BMT). We studied the effect of a busulfan (Bu) and cyclophosphamide (Cy) marrow transplant conditioning regimen, without radiation, on MK‐CSA production. Initial screening of MK‐CSA was done on previously collected and banked sera from 14 BMT patients. MK‐CSA was expressed as the ability to stimulate growth of megakaryocyte progenitors (CFU‐MK) in standard plasma clot cultures. In the initial samples, MK‐CSA peaked at day 7. This preliminary data led to a prospective study of MK‐CSA and clinical parameters in seven allogeneic recipients. MK‐CSA activity increased from day −7 pre‐transplant (2.9 ± 1.7 CFU‐MK/105 NATD, mean ± SD) to day O (10.3 ± 4.7 CFU‐MK) and peaked by day 9 post‐transplant (20.6 ± 6.4 CFU‐MK). MK‐CSA activity decreased in all seven patients by day 21 at which time five of seven patients studied had recovery of platelet counts to greater than 100 ± 109/l. MK‐CSA activity rose rapidly in both groups of sera after the initiation of this non‐irradiation. BMT preparative regimen. High MK‐CSA levels, early after transplant, may contribute to the rapid platelet recovery in some patients.