Transfusion of bone marrow red cells during bone marrow harvests

Large volumes of bone marrow may be required for certain types of autologous bone marrow transplants. The present study was done to determine whether red cells obtained during a bone marrow harvest would be useful in reducing homologous transfusion requirements. A group of patients receiving standard transfusion support during the harvest (group 1) was compared to a group that received processed bone marrow red cells (PBMRBC) (group 2). Using the Cobe 2991 cell processor, 90% of the harvested bone marrow red cells were extracted and transfused during the procedure. Group 2 received a median of 1500 ml of blood processed from the bone marrow or 413 ml (volume of marrow processed x hematocrit) of red cells. Infusion of the PBMRBC reduced the homologous transfusion requirement from 6.5 units to 3.0 units (p = 0.02). In addition, group 1 had a 20% decrease in hematocrit following transfusion compared to the pre-harvest hematocrit, as opposed to an 8% decrease in group 2 (p = 0.02). This study indicates that PBMRBC can reduce the homologous transfusion requirements during an autologous bone marrow harvest.     

No narcosis for bone marrow harvest in autologous bone marrow transplantation

Summary A prospective study with mild general analgesia and sedation together with local anesthesia during bone marrow harvest was performed. Thirty-one patients underwent 33 bone marrow collections. Pretreatment consisted of 100 mg meperidine i.m. and 20 mg diazepam i.m. 1 h before start of procedure. Eight patients got additional meperidine and diazepam during the procedure, all patients got lidocaine 1% locally. A mean volume of 1.321 was obtained with 42.5 punctures. Twenty-two patients had no complications, 4 vomited, 4 had easily correctable hypotension of short duration, one got oxygen for cyanosis of short duration. Acceptance was good in 23 patients, in 6 reasonably well, in two bad. Only one patient experienced pain problems, due to suction. Anxiety was no major problem due to good information before the procedure and mild sedation.This form of anesthesia for bone marrow collection is a safe procedure, it is generally well accepted by the patient and it can be performed on an out-patient basis.     

Alcohol-induced bone marrow damage. A bone marrow study in alcohol-dependent individuals

Bone marrow biopsies from 30 alcohol-dependent individuals hospitalized for detoxification were investigated. Typical alcohol-induced bone marrow changes were found and served to define alcohol-induced bone marrow damage as a nosological entity. The findings took the form of heightened ineffective erythropoiesis associated with impaired iron utilization, vacuolated proerythroblasts, multinuclear erythroblasts, megaloblasts and iron-containing plasma cells as well as vacuolated precursor cells of the granulocytopoietic series. In the differential diagnosis, alcohol-induced bone marrow damage is to be distinguished from the myelodysplastic syndrome of the RA and RARS form. Alcohol-induced bone marrow damage is reversible. Bone marrow cell cultures performed in our cases are normal, showing that the toxic defect probably does not reside in the stem cell but is more peripheral. Normal bone marrow cell culture may be a typical feature of alcohol-induced bone marrow damage.     

Allogeneic bone marrow transplantation

The probability of long term survival for allogeneic graft patients was 63% for ALL, 64% for ANL and 40% for CML in the 1st remission or 1st chronic phase of each leukemia. The major causes of death were interstitial pneumonia, relapse of leukemia and infections. On relationship of GVHD and the long term survival, the probability of 5 years survival was 38%, 47% and 25% in grade O, I and II-IV of acute GVHD respectively. And the relationship between the relapse rate and GVHD, the patients with both of acute and chronic GVHD showed the lowest relapse rate 15.9%, the patients without GVHD showed the highest relapse rate 37.8% and the patients with either of GVHD showed the rate of between those of two groups. This may suggest that GVHD both acute and chronic might have an ability that can suppress the relapse of leukemia, i.e. GVL reaction. Interstitial pneumonia occurred in 32% of allograft patients and was often lethal complication (53%). Among many of prophylaxis tested, the followings were effective, a lower dose rate of total body irradiation, the selection of CMV-seronegative platelets donor, and the prophylactic administration of anti-CMV high titer globulin. Colony stimulating factor of human urine was also effective for shortening the granulopenic period after transplantation to prevent severe infections.     

Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation

Dyskeratosis congenita is recognized by its dermal lesions and constitutional aplastic anemia in some cases. We report successful allogeneic bone marrow transplantation in two siblings with this disease from their sister, and their long term follow-up. We used reduced doses of cyclophosphamide and busulfan for conditioning instead of total body irradiation. Also, we report late adverse effects of transplantation which are not distinguishable from the natural course of disease.     

Amiodarone-induced bone marrow granulomas

Amiodarone hydrochloride, a class III antiarrhythmic agent used to treat supraventricular and ventricular cardiac dysrhythmias. In this report we describe two patients receiving amiodarone for atrial fibrillation who underwent bone marrow biopsies to investigate paraproteinaemia (case 1) or severe thrombocytopenia (case 2). Multiple bone marrow granulomas were found in both patients, without evidence of any other cause. In both patients the granulomas disappeared after amiodarone withdrawal, suggesting a direct association.     

Allogeneic bone marrow transplantation in children failing prior autologous bone marrow transplantation

Twenty-three children with de novo acute myelogenous leukemia (AML) (n = 20), secondary AML (n = 1), or non-Hodgkin's lymphoma (NHL) (n = 2) underwent allogeneic bone marrow transplantation (alloBMT) for graft failure (n = 1) or recurrent malignancy (n = 22) between February 1992 and August 1999 following autologous BMT (ABMT). Induction chemotherapy was given to 14 patients and nine patients went directly to alloBMT. Five received marrow from matched siblings, 14 from matched unrelated donors and four from mismatched family members. Conditioning regimens included cyclophosphamide, cytarabine, and total body irradiation. Nine patients are alive disease-free between 627 and 2433 days (1.7-6.7 years) post BMT resulting in a 4-year DFS of 39%. Eight patients relapsed at a median of 206 days (range, 35-669 days) post alloBMT and all eventually died. Eight patients (two of whom also relapsed) died of RRT. Although RRT and relapse remain significant problems, a significant percentage of pediatric patients failing ABMT may be cured with alloBMT.     

Antibody-mediated marrow failure after allogeneic bone marrow transplantation

Marrow graft failure observed in association with histocompatibility differences between donor and recipient is often attributed to rejection mediated by host-derived cytolytic T lymphocytes. The data presented in this report indicate that persistent host antibodies specific for donor antigen may also mediate graft failure, either by antibody-dependent cell-mediated cytotoxicity (ADCC), or complement- mediated cytotoxicity. In the case of HLA Class I disparity, where all donor cells express the target antigen, the presence of alpha-donor antibody was associated with complete graft failure and death. In the case of ABO blood group antigen disparity, the presence of alpha-donor antibody resulted in erythroid hypoplasia. The latter cases proved informative insofar as they established that host antibodies could persist for more than 18 months after chemoradiotherapy and impair marrow function.     

Cytokine production by bone marrow mononuclear cells in inherited bone marrow failure syndromes

Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond‐Blackfan anaemia (DBA), and Shwachman‐Diamond syndrome (SDS) are characterized by the progressive development of bone marrow failure. Overproduction of tumour necrosis factor‐α (TNF‐α) from activated bone marrow T‐cells has been proposed as a mechanism of FA‐related aplasia. Whether such overproduction occurs in the other syndromes is unknown. We conducted a comparative study on bone marrow mononuclear cells to examine the cellular subset composition and cytokine production. We found lower proportions of haematopoietic stem cells in FA, DC, and SDS, and a lower proportion of monocytes in FA, DC, and DBA compared with controls. The T‐ and B‐lymphocyte proportions were similar to controls, except for low B‐cells in DC. We did not observe overproduction of TNF‐α or IFN‐γ by T‐cells in any patients. Induction levels of TNF‐α, interleukin (IL)‐6, IL‐1β, IL‐10, granulocyte colony‐stimulating factor, and granulocyte‐macrophage colony‐stimulating factor in monocytes stimulated with high‐dose lipopolysaccharide (LPS) were similar at 4 h but lower at 24 h when compared to controls. Unexpectedly, patient samples showed a trend toward higher cytokine level in response to low‐dose (0·001 μg/ml) LPS. Increased sensitivity to LPS may have clinical implications and could contribute to the development of pancytopenia by creating a chronic subclinical inflammatory micro‐environment in the bone marrow.