D. A. G. Galton

Clinical and laboratory features of de novo acute myeloid leukaemia with trilineage myelodysplasia

Primary myelodysplastic syndromes progress to acute myeloid leukaemia (AML) in about 30% of cases. We have sought evidence of pre‐existing trilineage myelodysplasia (TMDS) using the FAB criteria (1982) in 160 consecutive cases of primary de novo AML. TMDS was found in 24 cases (15%) including two of 33 cases of Ml (6%), four of 40 cases of M2 (10%), none of 18 cases of M3, five of 31 cases of M4 (15%), six of 30 cases of M5 (20%), all of six cases of M6 and one of two cases of M7.

T-lymphoblastic leukaemia: a distinct variant of acute leukaemia.

Two cases of acute lymphoblastic leukaemia (A.L.L.) of T-cell type are reported. Clinically they were characterized by very high peripheral blood blast cell counts at presentation, the early development of meningeal leukaemia, and relative resistance to treatment with combination chemotherapy. Leukaemic cells from both patients lacked all the B-cell markers investigated, but 60-65% of their cells formed rosettes with sheep red cells. Cytochemical and surface structure studies helped to define additional features of these cells and confirmed their T-cell nature. It seems that this variant of A.L.L. may not be uncommon and that it can be distinguished on clinical and immunological grounds from the usual type of A.L.L. which runs a less aggressive course and lacks B- or T-cell markers.

Autografting for patients with chronic myeloid leukaemia in chronic phase: peripheral blood stem cells may have a finite capacity for maintaining haemopoiesis

Summary. We treated 14 patients with Ph‐chromosome‐positive chronic myeloid leukaemia still in chronic phase by autografting with blood‐derived haemopoietic stem cells. Eleven patients were autografted electively after cytoreductive treatment with busulphan (16 mg/kg) and melphalan (60 mg/m2) and three were autografted after marrow cells from HLA‐identical sibling donors had failed to engraft. In 13 patients haemopoiesis recovered; one failed to engraft and died 114 d after autografting. Two other patients became pancytopenic and received further stem cell transfusions at 3 and 40 months respectively after first autografting. One patient entered lymphoid transformation and died 14 months after autografting. Twelve patients survive at a median of 41 months (range 24–53) after autografting. Nine of the survivors have required further chemotherapy after autografting and four of the nine were electively autografted on a second occasion. Three patients surviving after autografting for 28, 43 and 53 months respectively have not required further chemotherapy. In two of these patients haemopoiesis is now predominantly Ph‐negative. We conclude that autografting in chronic phase might prolong survival in some cases by reducing the size of the leukaemic stem cell population. The fact that initially successful grafts failed in two patients suggests that blood‐derived stem cells may have a finite potential for self‐replication.

Myelodysplastic relapse of de novo acute myeloid leukaemia with trilineage myelodysplasia: a previously unrecognized correlation

Summary We describe the occurrence of an unusual mode of relapse in six of 24 patients who presented with de novo acute myeloid leukaemia (AML) associated with trilineage myelodysplasia (TMDS). After the induction of complete remission (CR) by intensive chemotherapy in five patients and following bone marrow transplantation (BMT) in one, the myelodysplastic state, but not overt AML, recurred. Relapse of myelodysplasia occurred at a median of 147 weeks (50–520) from presentation and in two instances was followed a year later by AML. In five cases, myelodysplastic relapse was treated with low‐dose cytosine arabinoside given alone or with other chemotherapeutic agents. Three patients remain in CR after 1,2 and 5 years. The reappearance of myelodysplastic features in these six patients was strongly correlated with the presence of TMDS at presentation of the AML. It was not observed once in the 136 AML patients, treated similarly, who did not have associated TMDS at presentation (P<0.001). Thus, relapse with myelodysplasia is not an effect of chemotherapy as has been previously postulated.

Prolymphocytic Leukaemia: an Ultrastructural Study of 22 Cases

. Twenty‐two cases of prolymphocytic leukaemia (PLL) have been studied by transmission electron microscopy (TEM); 17 had B‐cell surface markers (B‐PLL) and five had T‐cell characteristics (T‐PLL). The predominant cell, the prolymphocyte, has distinct features which were common to all cases: it is a relatively large lymphoid cell with a prominent nucleolus, well condensed peripheral nuclear chromatin and a variable amount of heterochromatin in intranuclear clumps.

Multiple‐drug chemotherapy for acute leukemia. The TRAMPCOL regimen: Results in 86 patients

A combination of eight cytotoxic drugs, administered simultaneously, has been used in 86 cases of acute leukemia. The regimen, designated TRAMPCOL, incorporated thioguanine, rubidomycin, (daunorubicin), cytosine arabinoside, methotrexate, prednisolone, cyclophosphamide, vincristine, and usually L‐asparaginase. Treatment was administered in five‐day pulses with treatment‐free intervals varying from nine to 23 days. Subjective and objective toxic effects were not more severe than those seen with two‐ and four‐drug regimens previously employed. Substantial clinical and hematologic improvement occurred in 8/19 patients with chronic granulocytic leukemia (CGL) in acute transformation. Complete clinical and hematologic remission (CR) was achieved in 3/7 patients with untreated acute myeloid leukemia (AML), 5/19 patients with AML who had failed to achieve CR with other therapy, and 4/18 patients with AML in relapse after CR obtained with regimens other than TRAMPCOL. CR occurred in 15/17 patients with acute lymphocytic leukemia (ALL), most of whom had had multiple previous relapses. CR was not achieved in four patients with AML superimposed on pre‐existing myeloproliferative disorders. The TRAMPCOL regimen merits further evaluation in CGL after acute transformation, as a primary treatment for AML, and as therapy for ALL 1) in relapse, 2) in adults, 3) in children with adverse prognostic features, and 4) in T‐cell ALL. Cancer 40:20–29, 1977.

Prolonged remission maintenance in acute myeloid leukaemia.

Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia.

Chronic Granulocytic Leukaemia: Multiple-drug Chemotherapy for Acute Transformation

The response to 60 trials of therapy in 50 patients with chronic granulocytic leukaemia (C.G.L.) in acute transformation is reported. None of the 13 patients who received single-agent chemotherapy had a satisfactory response. The use of two drugs in combination produced only one satisfactory response in 30 patients. Various types of multiple-drug treatments in eight patients achieved one good response which lasted four months. In contrast when nine patients with rapidly progressive acute transformation of C.G.L. received a regimen—TRAMPCO(L)—incorporating seven or eight drugs (thioguanine, daunorubicin, cytarabine, methotrexate, prednisolone, cyclophosphamide, and vincristine, with or without L-asparaginase colaspase) five improved significantly. Four patients had a good clinical and haematological response with survival for over three, eight, over 12, and 14 and a half months; and one patient had a partial response. Toxicity was not extreme and maintenance therapy with the same regimen was given on an outpatient basis. TRAMPCO(L) seems superior to previously reported regimens and should be considered for rapidly progressive transformation of C.G.L. especially when simpler treatments have failed.

Osteolytic tumors in acute megakaryoblastic leukemia

A patient with soft tissue tumors and osteolytic bone lesions produced by acute megakaryoblastic leukemia is described. This appears to be the first report of this complication. The management and significance of this presentation are discussed.

Regression of intracerebral lesions in T prolymphocytic leukaemia treated with intravenous deoxycoformycin

A case of T‐prolymphocytic leukaemia (T‐PLL) presenting with deafness and confusion is reported. Computerised tomography (CT) of the head showed several well‐defined, rounded, high attenuation areas in the temporal, parietal and occipital regions of the brain substance that were suggestive of metastases. Treatment with weekly intravenous deoxycoformycin produced complete resolution of the CT abnormalities together with haematological evidence of disease regression 6 weeks after treatment was started.